In SPGF52; does not affect protein expression; impairs polycomplex formation between SIX6OS1 and SYCE1.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
Helical; Anchor for type IV membrane protein
In ALS8 and SMAPAD; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway; affects interaction with RMDN3; affects cellular calcium homeostasis; induces mislocalization to the non-ER compartments; enhances homodimerization.
In ALS8; it forms insoluble cytosolic aggregates; cannot activate the UPR pathway through ERN1/IRE1 induction; results in ubiquitinated aggregates accumulation and cell death.
Prevents binding to the FFAT motif in target proteins; when associated with D-87.
Prevents binding to the FFAT motif in target proteins; when associated with D-89.
Vesicle-associated membrane protein-associated protein B/C
Glutamine amidotransferase-like class 1 domain-containing protein 3, mitochondrial
Putative glutamine amidotransferase-like class 1 domain-containing protein 3B, mitochondrial
Aryl hydrocarbon receptor nuclear translocator
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Hairy/enhancer-of-split related with YRPW motif protein 1
Associated with asthma and atopy; retains the ability to associate with HDL particles.
Impairs the association with HDL particles.
Impairs the association with LDL particles.
In PAFAD; loss of function; risk factor for coronary arthery disease and stroke.
Platelet-activating factor acetylhydrolase
Reduces the association with HDL particles.
Reduces the association with LDL particles.
Retains the ability to associate with HDL particles.
Associated with occlusive-cerebrovascular disease; Isehara-1.
Heat shock transcription factor, X-linked
Helical; Signal-anchor for type II membrane protein
In a breast cancer sample; somatic mutation.
Probable E3 ubiquitin-protein ligase TRIML1
In OBLFC1; severely impairs the stabilization of microtubules.
In TBHS1; has an abnormal punctate expression pattern; has a drastically reduced ability to stabilize microtubules.
In TBHS1; unknown pathological significance.
No effect on the stabilization of microtubules.
Cytoplasmic dynein 2 intermediate chain 1
In SRTD8; Reduces interaction with IFT proteins.
In SRTD8; does not affect interaction with DYNC2I2.
In CMS24; unknown pathological significance.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3
In SMDCD; strong reduction in protein levels and marked increase in cellular phosphatidylinositol 4,5 bisphosphate levels in patient cells.
Does not strongly affect phosphorylation status; when associated with F-105.
Does not strongly affect phosphorylation status; when associated with F-137.
Induces a complete cytoplasmic redistribution.
Induces a partial cytoplasmic redistribution.
Strongly reduces phosphorylation and induces the formation of a constitutive SCF(NIPA) E3 complex that degrades CCNB1 at G2/M phase and delays mitotic entry.
Abolished SUMOylation; when associated with R-527.
Abolished SUMOylation; when associated with R-633.
Abolishes interaction with DVL2 and SUDS3 as well as DVL2 nuclear translocation.
Decreased phosphorylation leading to increased stability of the protein; when associated with A-373.
Decreased phosphorylation leading to increased stability of the protein; when associated with A-428.
Phosphomimetic mutant; decreased phosphorylation leading to decreased stability of the protein; when associated with D-373.
Phosphomimetic mutant; decreased phosphorylation leading to decreased stability of the protein; when associated with D-428.
BUB3-interacting and GLEBS motif-containing protein ZNF207
In BuGZAA: Abolishes interaction with BUB3.
Calcium-binding tyrosine phosphorylation-regulated protein
Decreases phosphorylation and interaction with GSK3B. Abolishes phosphorylation and decreases interaction with GSK3B; when associated with A-151.
Decreases phosphorylation. Abolishes phosphorylation; when associated with A-155.
Does not affect phosphorylation. Does not affect phosphorylation; when associated with A-154.
Does not affect phosphorylation. Does not affect phosphorylation; when associated with A-159.
N-linked (GlcNAc...) (complex) asparagine
Abolishes interaction with VTA1, MITD1 and USP8; diminishes interaction with VPS4A.
Diminishes interaction with VPS4A. Greatly diminishes interaction with VPS4A and abolishes interaction with VTA1; when associated with A-353. Greatly diminishes interaction with VPS4A; when associated with A-360.
Diminishes interaction with VPS4A. Greatly diminishes interaction with VPS4A and abolishes interaction with VTA1; when associated with D-326. Greatly diminishes interaction with VPS4A; when associated with D-323.
Diminishes interaction with VPS4A. Greatly diminishes interaction with VPS4A; when associated with A-353.
Diminishes interaction with VPS4A. Greatly diminishes interaction with VPS4A; when associated with D-326.
In isoform 2, isoform 3, isoform 4 and isoform 6.
Apoptosis-resistant E3 ubiquitin protein ligase 1
Failure to form ubiquitin thioester complex.
Telomeric repeat-binding factor 2-interacting protein 1
Interchain (with C-657 in SUN1); alternate
Coiled-coil domain-containing protein 102A
Found in a patient with progressive myoclonic epilepsy type 2 also carrying two mutations in EPM2B.
No effect on interaction with EPM2A; when associated with A-85.
No effect on interaction with EPM2A; when associated with A-87.
No interaction with EPM2A; when associated with A-247.
No interaction with EPM2A; when associated with A-250.
Protein phosphatase 1 regulatory subunit 3C
Leucine-rich repeat-containing protein 26
No effect on transcriptional repression.
Transcription elongation factor A protein-like 1
Translocating chain-associated membrane protein 1
Impaired binding to cargo proteins containing a PTS2 peroxisomal targeting signal.
Impaired interaction with PEX5, leading to decreased peroxisomal import of proteins containing a PTS2 peroxisomal targeting signal.
In RCDP1; unknown pathological significance.
Abolishes interaction with NAA10 and NAA15.
Reduces ability to inhibit NAA10-NAA15 complex-mediated N-terminal acetylation, which results in increased N-terminal acetylation.
Reduces ability to inhibit NAA10-NAA15 complex-mediated N-terminal acetylation, which results in increased N-terminal acetylation; when associated with A-35.
Reduces ability to inhibit NAA10-NAA15 complex-mediated N-terminal acetylation, which results in increased N-terminal acetylation; when associated with A-38.
Abolished diacylglycerol O-acyltransferase activity.
Decreased diacylglycerol O-acyltransferase activity.
Does not affect diacylglycerol O-acyltransferase activity.
In DIAR7; unknown pathological significance.
Reduced diacylglycerol O-acyltransferase activity.
Slightly decreased diacylglycerol O-acyltransferase activity.
Strongly reduced diacylglycerol O-acyltransferase activity.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)
Loss of melanoma cell invasion; when associated with A-641; A-646; A-665; A-668 and A-679.
Loss of melanoma cell invasion; when associated with A-641; A-646; A-665; A-668 and A-683.
Loss of melanoma cell invasion; when associated with A-641; A-646; A-665; A-679 and A-683.
Loss of melanoma cell invasion; when associated with A-641; A-646; A-681; A-679 and A-683.
Loss of melanoma cell invasion; when associated with A-641; A-665; A-681; A-679 and A-683.
Loss of melanoma cell invasion; when associated with A-646; A-665; A-681; A-679 and A-683.
Promotes melanoma cell invasion; when associated with D/E-628; D/E-633; D/E-652; D/E-668 and D/E-679.
Promotes melanoma cell invasion; when associated with D/E-628; D/E-633; D/E-652; D/E-668 and D/E-683.
Promotes melanoma cell invasion; when associated with D/E-628; D/E-633; D/E-652; D/E-679 and D/E-683.
Promotes melanoma cell invasion; when associated with D/E-628; D/E-633; D/E-668; D/E-679 and D/E-683.
Promotes melanoma cell invasion; when associated with D/E-628; D/E-652; D/E-668; D/E-679 and D/E-683.
Promotes melanoma cell invasion; when associated with D/E-633; D/E-652; D/E-668; D/E-679 and D/E-683.
Alters protein structure. Nearly abolishes enzyme activity.
Myosin regulatory light chain 2, atrial isoform
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Inhibitor of nuclear factor kappa-B kinase subunit epsilon
Loss of autophosphorylation and of kinase activity.
Loss of kinase activity and loss of nuclear import.
Loss of sumoylation and loss of targeting to nuclear bodies.
Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization.
Loss of ubiquitination and decreased kinase activity. No effect on homodimerization.
Phosphoserine; by autocatalysis and IKKB
Complete redistribution from the nucleus to the cytoplasm; when associated with A-10; A-11; A-26; A-27; A-28; A-71; A-72; A-73 and A-74.
Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-27; A-71; A-72; A-73 and A-74.
Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-28; A-71; A-72; A-73 and A-74.
Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-27; A-28; A-71; A-72; A-73 and A-74.
Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-26; A-27; A-28; A-71; A-72; A-73 and A-74.
Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-11; A-26; A-27; A-28; A-71; A-72; A-73 and A-74.
Redistributes from the nucleus to both nucleus and cytoplasm; when associated with A-71; A-72 and A-73. Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-27; A-28; A-71; A-72 and A-73.
Redistributes from the nucleus to both nucleus and cytoplasm; when associated with A-71; A-72 and A-74. Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-27; A-28; A-71; A-72 and A-74.
Redistributes from the nucleus to both nucleus and cytoplasm; when associated with A-71; A-73 and A-74. Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-27; A-28; A-71; A-73 and A-74.
Redistributes from the nucleus to both nucleus and cytoplasm; when associated with A-72; A-73 and A-74. Complete redistribution from the nucleus to the cytoplasm; when associated with A-9; A-10; A-11; A-26; A-27; A-28; A-72; A-73 and A-74.
Major intrinsically disordered NOTCH2-binding receptor 1-like
Cytochrome c oxidase assembly protein COX20, mitochondrial
In MC4DN11; reduced protein expression; defective mitochondrial respiratory chain complex IV assembly; decreased interaction with MT-CO2/COX2; increased interaction with TMEM177.
Disrupts interaction with VPS26; no effect on interaction with VPS29.
Disrupts interaction with VPS29. Does not effect interaction with VPS26.
Found in a consanguineous family with intellectual disability; unknown pathological significance.
Found in a patient with Parkinson disease.
In PARK17; decreases interaction with WASHC2C, FKBP15 and the WASH complex; impairs recruitment of the WASH complex to endosomes; shows reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows a progressive reduction in neurite length and branching.
Vacuolar protein sorting-associated protein 35
Mothers against decapentaplegic homolog 5
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Probable ubiquitin carboxyl-terminal hydrolase FAF-Y
Radical S-adenosyl methionine domain-containing protein 1, mitochondrial
Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma patient; loss of ability to induce apoptosis.
Confers susceptibility to pheochromocytoma; found as germline mutation in a pheochromocytoma family; loss of ability to induce apoptosis.
In a medulloblastoma sample; somatic mutation; loss of ability to induce apoptosis.
In a pheochromocytoma sample; loss of ability to induce apoptosis.
Acetyl-coenzyme A synthetase, cytoplasmic
Protein phosphatase 1 regulatory subunit 3G
Glutamine--fructose-6-phosphate aminotransferase [isomerizing] 1
Able to hydrolyze ATP and display some protein kinase activity.
In AI1G; impaired folding of the protein; abolishes ability to activate FAM20C protein kinase activity.
Does not impair interaction with AGO2; when associated with A-313; A-345; A-370 and A-420.
Does not impair interaction with AGO2; when associated with A-313; A-345; A-370 and A-483.
Does not impair interaction with AGO2; when associated with A-313; A-345; A-420 and A-483.
Does not impair interaction with AGO2; when associated with A-313; A-370; A-420 and A-483.
Does not impair interaction with AGO2; when associated with A-345; A-370; A-420 and A-483.
Trinucleotide repeat-containing gene 6A protein
Reversion-inducing cysteine-rich protein with Kazal motifs
In AT3D; Dreux; complete loss af heparin binding.
In AT3D; Tours/Alger/Amiens/Toyama/Paris-1/Paris-2/Padua-2/Barcelona-2/Kumamoto/Omura/Sasebo; lacks heparin-binding ability.
In AT3D; severely decreased antithrombin activity.
In AT3D; severely decreased antithrombin activity; low affinity for heparin.
In AT3D; type-I; does not undergo post-translational glycosylation.
In AT3D; type-I; severely decreased antithrombin activity.
In AT3D; type-II; Budapest-3/Budapest-7.
In AT3D; type-II; Charleville/Sudbury/Vicenza/Cambridge-1.
In AT3D; type-II; Denver/Milano-2; deprived of inhibitory activity.
In AT3D; type-II; Glasgow/Sheffield/Chicago/Avranches/Kumamoto-2; increases affinity for heparin; deprived of inhibitory activity.
In AT3D; type-II; Hamilton/Glasgow-2; reduces interaction with thrombin by 90%.
In AT3D; type-II; Nagasaki; defective heparin binding associated with thrombosis.
In AT3D; type-II; Pescara; deprived of inhibitory of activity.
In AT3D; type-II; Rouen-1/Padua-1/Bligny/Budapest-2; lack of heparin-binding properties.
In AT3D; type-II; Rouen-2; lack of heparin-binding properties.
In AT3D; type-II; Rouen-3; lack of heparin-binding properties.
In AT3D; type-II; Rouen-4; lack of heparin-binding properties.
In AT3D; type-II; Rouen-6; increases affinity for heparin.
In AT3D; type-II; Truro; increases affinity for heparin.
In AT3D; type-II; Utah; deprived of inhibitory activity.
In AT3D; type-II; lacks heparin-binding ability.
Reduces interaction with thrombin by 80%.
Reduces interaction with thrombin by 99%.
In VCTRL; unknown pathological significance.
Loss of PQBP1-binding; when associated with A-192 and A-197.
Loss of PQBP1-binding; when associated with A-192 and A-198.
Loss of PQBP1-binding; when associated with A-197 and A-198.
Deleted in lung and esophageal cancer protein 1
(Microbial infection) ADP-riboxanated arginine
Abolished ADP-riboxanation by C.violaceum CopC.
Abolishes binding to FLASH. Induces NF-kappa-B activation.
Associated with protection against breast cancer; also associated with a lower risk of cutaneous melanoma.
Impaired CDK1-mediated phosphorylation and enhanced apoptosis.
Abolishes localization to spindle microtubules, no effect on localization to centrosomes and kinetochores; when associated with A-1939.
Abolishes localization to spindle microtubules, no effect on localization to centrosomes and kinetochores; when associated with A-1942.
Found in a renal cell carcinoma sample; somatic mutation.
In IECEE1; results in constitutive phosphatase activity in the absence of calmodulin.
In IECEE1; unknown pathological significance.
Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341.
Partial loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with F-341.
Protein phosphatase 3 catalytic subunit alpha
Resistant to cyclosporin A-mediated inhibition. Loss of Ca(2+)-mediated transcription factor NFAT activation; when associated with N-288, A-228 or 328-V--R-332 DEL. Partial loss in Ca(2+)-mediated transcription factor NFAT activation; when associated with F-288.
Natural cytotoxicity triggering receptor 2
Coiled-coil domain-containing protein 116
Cyclic AMP-responsive element-binding protein 3-like protein 4
Processed cyclic AMP-responsive element-binding protein 3-like protein 4
Found in a colorectal sample; somatic mutation.
In CRCS10; associated with disease susceptibility.
In MDPL; the mutant enzyme lacks DNA polymerase ability; has decreased exonuclease activity; can bind DNA but is unable to interact with and incorporate dNTPs.
Loss of exonuclease activity. No effect on DNA polymerase activity.
Impairs SMN binding to RPP20/POP7. Abolishes the interaction with ELAVL4. Abolishes interaction with SNRPD1 and SNRPD3. Impairs binding to substrate containing dimethylated arginine.
Impairs binding to substrate containing dimethylated arginine.
Impairs homooligomerization and GEMIN8 binding.
In SMA1; abolishes SMN1 binding to RPP20/POP7 and severely impairs binding to SNRPB, GEMIN8 and homooligomerization.
In SMA1; abolishes the interaction with ELAVL4.
In SMA1; slightly reduces SMN binding to RPP20/POP7. Impairs homooligomerization and axon localization.
In SMA2 and SMA3; Impairs SMN1 binding to RPP20/POP7, GEMIN8 and homooligomerization.
In SMA2; reduces SMN binding to Sm proteins; abolishes the interaction with ELAVL4.
In SMA3; reduces SMN binding to Sm proteins.
In SMA3; slightly reduces SMN binding to RPP20/POP7.
In isoform SMN-delta5 and isoform SMN-delta57.
In isoform SMN-delta7 and isoform SMN-delta57.
Isoglutamyl cysteine thioester (Cys-Gln)
In CTRCT9; associated with macular hypoplasia and a generally hypopigmented fundus.
In CTRCT9; decreases oligomer formation.
In CTRCT9; delays HSP70 expression increase in response to heat shock.
In CTRCT9; forms inclusion bodies, decreases chaperone activity, decreases protein stability at 45 degrees Celsius and increases protein aggregate formation in response to DTT in vitro.
In CTRCT9; results in protein aggregation in the cytoplasm.
In CTRCT9; reverse phase-high-performance liquid chromatography suggests an increased hydrophobicity of the mutant protein; loss of chaperone activity of the mutant is seen in DL-dithiothreitol-induced insulin aggregation assay; fast protein liquid chromatography purification shows that the mutant protein has increased binding affinity to lysozyme.
In CTRCT9; unknown pathological significance.
In CTRCT9; unknown pathological significance; reduced chaperone-like activity in vitro.
In CTRCT9; zonular central nuclear cataract; reduced chaperone-like activity and increased membrane-binding capacity.
Signal recognition particle receptor subunit beta
In NPHLOP2; impairs the interaction with SLC34A1; causes a reduction of SLC34A1 amount on cell membrane and affects SLC34A1-dependent phosphate uptake.
In NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cAMP by PTH and inhibits phosphate transport.
In NPHLOP2; the mutant expressed in cultured renal cells increases the generation of cyclic AMP (cAMP) by parathyroid hormone (PTH) and inhibits phosphate transport.
Na(+)/H(+) exchange regulatory cofactor NHE-RF1
Abolishes repression on mRNA. Abolishes interaction with AGO2, PABPC1 and PUM2. Increases interaction with HSP90AA1.
Decreases repression on mRNA. Abolishes interaction with AGO2, HSP90AA1, PABPC1 and PUM2.
Decreases repression on mRNA. Decreases interaction with HSP90AA1. Abolishes interaction with PABPC1 and PUM2. Increases interaction with AGO2.
Found in patients with DRD; unknown pathological significance.
In HPABH4B and DRD; phenotype presenting with dystonia and myoclonus.
In HPABH4B; intermediate phenotype presenting with dystonia and motor delay.
In HPABH4B; severe hyperphenylalaninemia.
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1
Loss ability to induce the formation of actin clusters; induce the formation of long filopodia.
Loss ability to induce the formation of actin clusters; when associated with K-141; K-142 and K-146.
Loss ability to induce the formation of actin clusters; when associated with K-141; K-142 and R-145.
Loss ability to induce the formation of actin clusters; when associated with K-141; R-145 and K-146.
Loss ability to induce the formation of actin clusters; when associated with K-142; R-145 and K-146.
Cyclin-dependent kinase 2-associated protein 1
Guanine nucleotide-binding protein subunit beta-5
In LADCI; severe, but incomplete loss of activation of RGS9 GTPase activator activity, affecting the deactivation of D(2) dopamine receptor-mediated signaling; decreased stability; decreased RGS9 stabilization.
Asymmetric dimethylarginine; by PRMT1; alternate
Found in a patient with a neurodevelopmental disorder; unknown pathological significance.
Found in a patient with a neurodevelopmental disorder; unknown pathological significance; results in early developmental defects when expressed in zebrafish embryos.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in UFM1); alternate
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
In TEVANED1; results in severe early developmental defects when expressed in zebrafish embryos; results in defective cell cycle progression when expressed in zebrafish embryos.
In TEVANED2 and TEVANED3; unknown pathological significance; does not affect early development when expressed in zebrafish embryos.
In TEVANED2; results in severe early developmental defects when expressed in zebrafish embryos.
In TEVANED3; results in early developmental defects when expressed in zebrafish embryos.
In TEVANED4; results in early developmental defects when expressed in zebrafish embryos.
In TEVANED4; results in severe early developmental defects when expressed in zebrafish embryos.
N6-(2-hydroxyisobutyryl)lysine; alternate
N6-(beta-hydroxybutyryl)lysine; alternate
Omega-N-methylarginine; by PRMT1; alternate
Symmetric dimethylarginine; by PRMT5 and PRMT7; alternate
Signal-induced proliferation-associated 1-like protein 1
Loss of interaction with CUL2. No effect on MAP3K5 activation.
Dominant-negative mutant, reduced binding to integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding to CX3CR1, defective in ternary complex formation, integrin activation and fractalkine signaling and suppression of leukocyte recruitment in the peritonitis model in vivo; when associated with E-60.
Dominant-negative mutant, reduced binding to integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding to CX3CR1, defective in ternary complex formation, integrin activation and fractalkine signaling and suppression of leukocyte recruitment in the peritonitis model in vivo; when associated with E-61.
Little or no effect on binding to integrin ITGAV:ITGB3.
Little or no effect on binding to integrin ITGAV:ITGB3; when associated with A-78.
Little or no effect on binding to integrin ITGAV:ITGB3; when associated with A-83.
Loss of binding to CX3CR1 and ability to induce chemotaxis but no effect on binding to integrins.
Reduced binding to integrin ITGAV:ITGB3, but no effect on binding to CX3CR1; when associated with A-60.
Reduced binding to integrin ITGAV:ITGB3, but no effect on binding to CX3CR1; when associated with A-61.
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2
In a lung cancer cell line; no effect on proapoptotic activity.
In a lung cancer cell line; reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity.
Nearly abolishes interaction with EPRS1.
Reduced interaction with TP53, loss of TP53 activation and loss of proapoptotic activity.
Abolishes phosphorylation by ATM; when associated with A-337.
Abolishes phosphorylation by ATM; when associated with A-42.
Phospho-mimetic mutant that translocates to the nucleus in absence of genotoxic stress; when associated with D-337.
Phospho-mimetic mutant that translocates to the nucleus in absence of genotoxic stress; when associated with E-42.
Ubiquitin carboxyl-terminal hydrolase 10
Almost complete loss of alcaline phosphatase induction; in association with A-325.
Almost complete loss of alcaline phosphatase induction; in association with V-203.
Serine/threonine-protein kinase receptor
Strong induction of SMAD1 phosphorylation.
CDP-diacylglycerol--inositol 3-phosphatidyltransferase
In DHS2; no effect on plasma membrane localization; increases calcium-activated potassium channel activity.
Intermediate conductance calcium-activated potassium channel protein 4
No effect on heterodimer formation with SLC30A5 and no effect on zinc transport; when associated with A-205.
No effect on heterodimer formation with SLC30A5 and no effect on zinc transport; when associated with A-70.
No effect on heterodimer formation with SLC30A5 and no effect on zinc transport; when associated with H-201.
No effect on heterodimer formation with SLC30A5 and no effect on zinc transport; when associated with H-66.
DNA-directed RNA polymerase III subunit RPC6
In IMD101; unknown pathological significance.
Strongly impaired dsDNA-binding. No effect on interaction with POLR3C.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1
Slight decrease in NF-kappa-B activation.
Loss of phosphorylation. No effect on GDI1 and GDI2 binding. Reduced binding to CHM and CHML.
Phosphomimetic mutant. Loss of binding to GDI1, GDI2, CHM, and CHML.
Sperm protein associated with the nucleus on the X chromosome N5
ATP-binding cassette sub-family C member 6
Associated with lower plasma triglycerides and higher plasma HDL cholesterol.
Found in patient with putative diagnosis of PEX; uncertain pathological significance.
Found in patient with putative diagnosis of PEX; uncertain pathological significance; loss-of-function mutation; localization comparable to wild-type.
Found in patient with putative diagnosis of PEX; uncertain pathological significance; mutant protein is retained in the cytoplasm.
Found in patient with putative diagnosis of PXE; uncertain pathological significance.
Found in patient with putative diagnosis of PXE; uncertain pathological significance; localization comparable to wild-type.
Found in patient with putative diagnosis of PXE; uncertain pathological significance; loss-of-function mutation; localization comparable to wild-type.
In PXE; affects protein expression and trafficking; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.
In PXE; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.
In PXE; autosomal dominant and autosomal recessive.
In PXE; autosomal dominant and autosomal recessive; abolishes LTC4 and NEM-GS transport.
In PXE; autosomal dominant and autosomal recessive; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.
In PXE; autosomal dominant; abolishes LTC4 and NEM-GS transport.
In PXE; autosomal dominant; abolishes LTC4 and NEM-GS transport; does not affect plasma membrane localization; does not increase extracellular pyrophosphate levels.
In PXE; autosomal dominant; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.
In PXE; autosomal recessive; affects protein expression and trafficking.
In PXE; autosomal recessive; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the WT protein.
In PXE; autosomal recessive; protein level is 15-20% that of the WT proteins; maturation of glycan chains is not affected indicating normal trafficking from the endoplasmic reticulum to the cell membrane.
In PXE; does not change protein biosynthesis and folding.
In PXE; loss-of-function variant; localization comparable to wild-type.
In PXE; protein level is 15-20% that of the WT proteins; maturation of glycan chains is not affected indicating normal trafficking from the endoplasmic reticulum to the cell membrane.
Abolishes ubiquitin binding; loss of inhibitory activity on NF-kappa-B activation.
Putative uncharacterized protein encoded by LINC03041
In MC1DN32; due to a nucleotide substitution that results in exon 4 skipping or in missense variant W-144; patient cells contain both type of transcripts; transcript lacking exon 4 is the most abundant.
In MC1DN32; due to a nucleotide substitution that results in exon 4 skipping or missense variant W-144; patient cells contain both type of transcripts; transcript with the missense variant is the less abundant.
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial
IQ and AAA domain-containing protein 1-like
In HHT5; impaired protein processing and function.
Inactive, constitutively GDP-bound. Abolishes location at Golgi membranes. Impairs transport of ADRA2A and ADRA2B from the Golgi to the cell membrane.
Inactive, due to loss of GNP binding. Abolishes location at Golgi membranes. Impairs transport of ADRA2A and ADRA2B from the Golgi to the cell membrane.
Increases PGD2 synthesis. Loss of activation by calcium or magnesium ions.
Loss of activation by calcium or magnesium ions.
Reduces PGD2 synthesis by 99%. Loss of activation by calcium or magnesium ions.
Loss of PIP2 binding and loss of liposomal lysis activity. Decrease in fungal cell permeabilization. Impaired antifungal activity.
Loss of PIP2 binding and reduced liposomal lysis activity. Impaired antifungal activity. Decrease in fungal cell permeabilization.
No impact on PIP binding and liposomal lysis activity. Lack of antifungal activity. Lack of fungal cell permeabilization.
No impact on fungal cell permeabilization. Impaired antifungal activity.
No impact on fungal cell permeabilization. No impact on antifungal activity.
28S ribosomal protein S14, mitochondrial
Constitutive coactivator of PPAR-gamma-like protein 2
Abolishes interaction with NCOA2 without affecting interaction with GPS2; when associated with 268-A--A-273.
Abolishes interaction with NCOA2 without affecting interaction with GPS2; when associated with 438-A-A-439.
Biogenesis of lysosome-related organelles complex 1 subunit 1
11-beta-hydroxysteroid dehydrogenase type 2
Almost complete loss of enzyme activity.
In AME; abolishes enzyme activity; decreased half-life from 21 to 3 hours compared to wild-type, probably due to degradation via the proteasomal pathway.
In AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway.
In AME; decreases enzyme activity by 33%.
In AME; reduces enzyme activity by at least 95%.
In AME; reduces enzyme activity to about 6% of wild type.
In hypertension; decreases affinity for cortisol.
Abolishes autophosphorylation; impairs release of pre-40S trans-acting factors and rRNA processing; when associated with A-123.
Abolishes autophosphorylation; impairs release of pre-40S trans-acting factors and rRNA processing; when associated with A-246.
Does not affect autophosphorylation activity; when associated with A-335 and A-380. Does not affect the timing of metaphase-anaphase transition; when associated with A-335 and A-380.
Does not affect autophosphorylation activity; when associated with A-335 and A-548. Does not affect the timing of metaphase-anaphase transition; when associated with A-335 and A-548.
Does not affect autophosphorylation activity; when associated with A-380 and A-548. Does not affect the timing of metaphase-anaphase transition; when associated with A-380 and A-548.
In a renal clear cell carcinoma sample; somatic mutation.
Increases time spent in metaphase; when associated with D-335 and D-380.
Increases time spent in metaphase; when associated with D-335 and D-548.
Increases time spent in metaphase; when associated with D-380 and D-548.
Nuclear relocalization; when associated with A-400.
Nuclear relocalization; when associated with A-403.
In a colorectal cancer sample; somatic mutation.
Found in a clear cell renal carcinoma case; somatic mutation.
Disrupts interaction with COPG1 and association with coatomer; when associated with 211-A-A-212.
Disrupts interaction with COPG1 and association with coatomer; when associated with 215-A-A-216.
No decrease in binding to COPG1. Disrupts interaction with SEC23A.
Significant reduction in binding to COPG1.
Transmembrane emp24 domain-containing protein 10
Nucleoside diphosphate-linked moiety X motif 6
EGF-containing fibulin-like extracellular matrix protein 1
In DHRD; misfolded, accumulates in cells due to inefficient secretion; induces the formation of deposits between Bruch's membrane and the retinal pigment epithelium where it accumulates.
Greatly reduced transactivating activity.
Brefeldin A-inhibited guanine nucleotide-exchange protein 3
Enhanced basal kinase activity; when associated with Q-96, L-121, A-124, K-182 and A-184.
Enhanced basal kinase activity; when associated with R-48, L-121, A-124, K-182 and A-184.
Enhanced basal kinase activity; when associated with R-48, Q-96, A-124, K-182 and A-184.
Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and A-184.
Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, A-124 and K-182.
Enhanced basal kinase activity; when associated with R-48, Q-96, L-121, K-182 and A-184.
In CAFD1; decreased interaction with regulatory subunit PRKAR2B.
In PPNAD4; somatic mutation; the mutation results in cAMP-independent basal protein kinase activity and constitutive activation of protein kinase A.
cAMP-dependent protein kinase catalytic subunit alpha
Abolishes hormone binding and homodimerization.
Abolishes hormone binding. No effect on homodimerization.
Important for interaction with G proteins
In MCDJ; constitutively activated; constitutively increases adenylate cyclase-activating G-protein coupled receptor signaling pathway; decreases the degree of N-glycosylation; does not affect homodimerization.
In MCDJ; leads to agonist-independent cAMP formation which is less pronounced than that observed with the Pro-410 mutant.
Parathyroid hormone/parathyroid hormone-related peptide receptor
In CSNB1B; abolishes expression at the cell membrane.
No effect on location at the cell membrane.
In IMD56; loss of function mutation; the mutation results in defective trafficking of the protein, with misfolding, impaired processing and abnormal subcellular distribution rather than proper expression at the plasma membrane.
Guanylate cyclase soluble subunit alpha-1
Loss of packaging into COPII-coated vesicles of the IxM motif-containing cargos GOSR2 and STX5.
Cation channel sperm-associated auxiliary subunit epsilon
Uncharacterized protein C10orf67, mitochondrial
Found in a family with amyotrophic lateral sclerosis carrying a probable causative mutation in MATR3; unknown pathological significance.
In ADLD; unknown pathological significance; no effect on localization to nuclear lamina.
In MCPH26; decreased localization to nuclear lamina; changed nuclear envelope organization; increased aggregation.
In MCPH26; decreased localization to nuclear lamina; increased aggregation; changed nuclear envelope organization.
In MCPH26; decreased protein abundance; changed localization to nuclear lamina; changed nuclear envelope organization.
In MCPH26; increased aggregation; changed nuclear envelope organization.
No effect on localization to nuclear lamina.
Abolishes ubiquitination and impairs CHEK1-dependent degradation following checkpoint activation.
Abrogates 14-3-3 protein binding; increases binding to cyclin B1.
Abrogates binding to CCNB1; when associated with L-514.
Abrogates binding to CCNB1; when associated with L-520.
Abrogates interactions with BTRC and FBXW11 and prevents ubiquitination.
Abrogates phosphorylation by CHEK2 and infrared-induced degradation. Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-178; A-279 and A-293.
Increased stability following IR treatment.
Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-178 and A-279.
Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-178 and A-293.
Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-279 and A-293. Abrogates 14-3-3 protein binding.
Mimicks phosphorylation state, leading to promote degradation following IR treatment.
Prevents ubiquitination and subsequent degradation by the APC/C ubiquitin ligase complex.
Abolished 'Lys-63'-linked ubiquitination by RNF167.
About two-fold prolonged half-life in cycloheximide/CHX time course.
Cysteine sulfenic acid (-SOH) intermediate
Decreased affinity for leucine. Requires increased leucine concentration to dissociate from GATOR2 and activate TORC1 signaling.
Decreased alkylhydroperoxide reductase activity and loss of the ability to decrease intracellular reactive oxygen species. No effect on interaction with the GATOR2 complex. No effect on inhibition of TOR signaling.
Decreased alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway.
Decreased leucine-binding. Promotes interaction with RNF167.
Loss of interaction with GATOR2. No effect on leucine-binding. Unable to mediate leucine-induced inhibition of the TORC1 signaling pathway.
Loss of interaction with the GATOR2 complex. No effect on leucine-binding.
Loss of leucine-binding. Constitutively interacts with the GATOR2 complex.
Loss of leucine-binding. Promotes interaction with RNF167. Constitutively interacts with the GATOR2 complex.
No effect on ability to decrease intracellular reactive oxygen species.
No effect on alkylhydroperoxide reductase activity.
No effect on alkylhydroperoxide reductase activity. Altered ability to decrease intracellular reactive oxygen species. No effect on the ability to inhibit the TORC1 signaling pathway.
No effect on alkylhydroperoxide reductase activity. Loss of interaction with the GATOR2 complex. Unable to inhibit the TORC1 signaling pathway.
No effect on alkylhydroperoxide reductase activity. No effect on the ability to inhibit the TORC1 signaling pathway.
No effect on the ability to inhibit the TORC1 signaling pathway.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-373.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-376.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-385.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-387.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-409 and A-411.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-409 and A-415.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-411 and A-415.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-419 and A-422.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-419 and A-426.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with A-422 and A-426.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with C-128.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with E-113.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with L-259 and R-261.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and L-259.
No effect on the ability to inhibit the TORC1 signaling pathway; when associated with R-258 and R-261.
Nearly abolishes activation of pre-mRNA splicing. Abolishes interaction with WBP11.
Golgi-associated RAB2 interactor protein 3
In COXPD15 and MC1DN27; decreased methionyl-tRNA formyltransferase activity.
In COXPD15; loss of methionyl-tRNA formyltransferase activity.
Methionyl-tRNA formyltransferase, mitochondrial
Found in a patient with isolated coloboma; unknown pathological significance.
Found in a patient with susceptibility to restless legs syndrome.
Thrombospondin type-1 domain-containing protein 4
Tyrosine-protein phosphatase non-receptor type 5
In GHISID1; affects activation by growth hormone or interferon-gamma.
In GHISID2; exhibits strong growth hormone-induced phosphorylation, but no subsequent nuclear localization; when forming homodimers with the wild-type protein, may also prevent its nuclear localization following growth hormone-stimulation.
In GHISID2; loss of DNA-binding ability; when forming homodimers with the wild-type protein, may prevent wild-type binding to DNA; consequently, disruption of transcriptional activity.
Signal transducer and activator of transcription 5B
(Microbial infection) O-linked (Glc) threonine; by C.difficile toxins TcdA and TcdB
ADP-ribosylasparagine; by botulinum toxin
Abolishes binding to PKN1 and trafficking of EGF receptor.
Abolishes methylation, palmitoylation and prenylation.
No effect on internalization of EGF receptor but decreases trafficking of receptor to the lysosome with associated accumulation in late endosomes.
No effect on palmitoylation or prenylation.
No effect on prenylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-192.
O-linked (GlcNAc) tyrosine; by Photorhabdus PAU_02230
Reduced geranylgeranylation but no effect on farnesylation. Reduced palmitoylation. Abolishes palmitoylation; when associated with S-189.
S-farnesyl cysteine; in plasma membrane form
S-geranylgeranyl cysteine; in endosomal form
Activates decapping activity to 120% of wild-type.
In ARS; results in a severe decrease of decapase activity.
Increases decapping activity to 125% of wild-type.
Increases decapping activity to 140% of wild-type.
Increases decapping activity to 180% of wild-type.
Increases decapping activity to 250% of wild-type.
Inhibits nuclear export to the cytoplasm.
Loss of decapping activity. Does not inhibit cap structure and capped RNA binding. Preferentially hydrolyzes cap structure (m7GpppG) at least 2500-fold more efficiently than capped RNA (m7Gppp-RNA).
Strongly diminishes interaction with HIRA.
Strongly diminishes interaction with HIRA; when associated with E-138 and L-139.
Strongly diminishes interaction with HIRA; when associated with E-138 and L-140.
Strongly diminishes interaction with HIRA; when associated with E-139 and L-140.
In isoform S, isoform S-HOP1 and isoform VS.
Pituitary adenylate cyclase-activating polypeptide type I receptor
Sterile alpha motif domain-containing protein 12
Does not abolish electron transfer activity. Abolishes sensitivity to inhibition by lysine methyltransferase ETFBKMT.
Does not abolish electron transfer activity. Decreases sensitivity to inhibition by lysine methyltransferase ETFBKMT.
Does not abolish methylation by ETFBKMT.
Drastically increases interprotein electron transfer rates.
Electron transfer flavoprotein subunit beta
In GA2B; reduced electron transfer activity.
N6,N6,N6-trimethyllysine; by ETFBKMT; alternate
Severely impaired in complex formation with ACADM.
In MRT18; specifically impairs the response of JUN and FOS immediate early genes to serum mitogens by altering the interaction between enhancer-bound transcription factors TCF7L2 and ELK1 and the Mediator complex.
Mediator of RNA polymerase II transcription subunit 23
Cleavage and polyadenylation specificity factor subunit 1
In MYP27; unknown pathological significance.
Zinc finger and SCAN domain-containing protein 10
PiggyBac transposable element-derived protein 1
Abolishes N-glycosylation. Abolishes N-glycosylation; when associated with Q-121.
Does not affect glycosylation state. Abolishes N-glycosylation; when associated with Q-171.
Protease-associated domain-containing protein 1
In MDDGA11; affects subcellular localization.
In MDDGA11; does not affect subcellular localization.
UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2
Cilia- and flagella-associated protein 95
WAP four-disulfide core domain protein 2
In XLID101; the mutant is abnormally localized in aggregates or enclosed in cytoplasmic vesicles rather than being bound to microtubules.
Probable E3 ubiquitin-protein ligase MID2
The protein is normally bound to microtubules.
Loss of interaction with CD3Z. Alters LAT, PLCG1, VAV1 and LCP2 phosphorylation, MAP kinase signaling, Rac1 and JNK activation, intracellular calcium increase, activation of the nuclear factor for activation of T-cells and subsequent interleukin-2 expression which normally occur upon T-cells stimulation.
Does not affect RNA helicase activity of NEXT complex; when associated with A-673.
Does not affect RNA helicase activity of NEXT complex; when associated with A-674.
Does not affect RNA helicase activity of NEXT complex; when associated with A-675.
Does not affect RNA helicase activity of NEXT complex; when associated with A-676.
Does not alter RNA helicase activity of NEXT complex; when associated with A-662.
Does not alter RNA helicase activity of NEXT complex; when associated with K-666.
Impaired interaction with ZCCHC8; when associated with E-295.
Impaired interaction with ZCCHC8; when associated with E-299.
In PFBMFT5; decreased levels of mature TERC in patient cells consistent with impaired function in RNA processing; decreased levels of mutant protein in patient cells.
Loss of RNA helicase activity of NEXT complex; when associated with E-688.
Loss of RNA helicase activity of NEXT complex; when associated with E-692.
Reduced interaction with ZCCHC8; when associated with A-309.
Reduced interaction with ZCCHC8; when associated with E-313.
Zinc finger CCHC domain-containing protein 8
Zinc finger and SCAN domain-containing protein 29
In isoform 2, isoform 3, isoform 4 and isoform 5.
In isoform 2, isoform 4, isoform 5 and isoform 6.
Mitogen-activated protein kinase kinase kinase kinase 4
Ankyrin repeat domain-containing protein 26
Phosphoserine; by GSK3-alpha and GSK3-beta
No effect on cell morphology when overexpressed.
Patatin-like phospholipase domain-containing protein 5
In CPHD1; associated with less severe impairment of transactivation; has a similar DNA-binding affinity as the wild-type protein.
In CPHD1; associated with severe impairment of transactivation; has a greatly reduced DNA-binding affinity as the wild-type protein.
In CPHD1; reduces transactivation capacity on the GH1 gene; increases the functional binding on the GH1 promoter; increases the interaction with ELK1, LHX3 and PITX1.
In CPHD1; reduces transactivation capacity on the PRL gene; increases instability of the protein.
In CPHD1; transactivation capacity of this mutant is markedly decreased on the GH1; PRL, TSHB and POU1F1 genes; abolishes the functional interaction of POU1F1 on the PRL promoter with the coactivator CREBBP but not with the transcription factor LHX3; displays normal nuclear accumulation but a markedly decreased binding to a DNA response element.
Increases the interaction with LHX3 and PITX1. No effect on the interaction with ELK1.
Increases the interaction with LHX3. No effect on the interaction with ELK1.
No effect on the interaction with ELK1, LHX3 and PITX1.
Pituitary-specific positive transcription factor 1
Polypeptide N-acetylgalactosaminyltransferase 13
Does not undergo proteolytic processing.
In IRIDA; does not undergo proteolytic processing; loss of activity.
In IRIDA; no effect on HJV-mediated inhibition of HAMP transcription; no effect on catalytic activity; autoproteolytic and HJV processing are not affected.
In IRIDA; no effect on HJV-mediated inhibition of HAMP transcription; no effect on localization to the cell membrane; no effect on catalytic activity; HJV processing is not affected.
In IRIDA; reduced HJV-mediated inhibition of HAMP transcription; does not undergo proteolytic processing; impaired localization to the cell membrane; able to interact with HJV.
In IRIDA; reduced HJV-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HJV processing are impaired.
In IRIDA; reduced HJV-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; altered catalytic activity; autoproteolytic processing is reduced but it retains the ability to process HJV; able to interact with HJV.
In IRIDA; reduced HJV-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; loss of catalytic activity; no ability to process HJV.
In IRIDA; reduced HJV-mediated inhibition of HAMP transcription; reduced localization to the cell membrane; no effect on catalytic activity.
In IRIDA; reduced expression at the cell surface; partially retained in the Golgi apparatus; does not undergo proteolytic processing; able to interact with HJV; results in reduced inhibition of HAMP promoter.
In IRIDA; reduced proteolytic processing; reduced expression to plasma membrane; does not affect binding to HJV.
In IRIDA; results in reduced inhibition of HAMP promoter.
In IRIDA; severely reduced proteolytic processing; loss of activity.
In IRIDA; slightly reduced HJV-mediated inhibition of HAMP transcription; loss of catalytic activity; autoproteolytic and HJV processing are significantly reduced.
Abolishes iron-sulfur-binding and affects exonuclease activity; when associated with A-343.
Abolishes iron-sulfur-binding and affects exonuclease activity; when associated with A-346.
In CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL.
In LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL.
In LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm.
In LCA7; unknown pathological significance.
In RP; unknown pathological significance.
Rare variant; found in a patient with hypertrophic cardiomyopathy; unknown pathological significance.
2-2.5-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1. No change in repression activity in the presence of CRY1.
Basic helix-loop-helix ARNT-like protein 1
Enhanced PER1 reporter activity by CLOCK-BMAL1.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)
Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1.
Increased desensitization to CRY1, in the presence of CLOCK. Approximately 2-fold increase in CLOCK-BMAL1 transcriptional activity in the absence of CRY1; when associated with E-407.
Phosphomimetic mutant which severely impairs DNA binding and CLOCK-BMAL1 transcriptional activity.
Phosphomimetic mutant with no effect on DNA binding or CLOCK-BMAL1 transcriptional activity.
Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform
U6 snRNA-associated Sm-like protein LSm2
Abolishes interaction with ETV5. Abolished repression activity.
Abolishes interaction with ETV5. No effect on repression activity.
Abolishes phosphorylation. Abolishes degradation of FLNA. No effect on assembly into ubiquitin-protein ligase complex.
Phosphomimetic mutant. No effect on isoform 2 FLNA degradation. No effect on assembly into ubiquitin-protein ligase complex.
Putative sodium-coupled neutral amino acid transporter 8
In GLD; adult; reduction of activity; when associated with V-2105.
In GLD; infantile; significant reduction of activity.
In GLD; significant reduction of activity.
In GLD; unknown pathological significance.
Abolished cleavage at the N-terminus, leading to impaired activation and thiol protease activity. In P7-D2A mutant; abolished cleavage and activation, leading to decreased but mesureable activity; when associated with A-198.
Abolished phosphorylation by PAK2; when associated with A-173 and A-239.
Abolished phosphorylation by PAK2; when associated with A-30 and A-173.
Abolished phosphorylation by PAK2; when associated with A-30 and A-239.
Decreased ability to cleave PARP1 and PTGES3.
Decreased ability to cleave PARP1. Decreased RNA-binding.
Does not affect ability to cleave PARP1.
Does not significantly affect thiol protease catalytic activity.
Does not significantly affect thiol protease catalytic efficiency.
In dsCasp-7 mutant; unable to cleave DEVD and VEID peptides; when associated with F-276.
In dsCasp-7 mutant; unable to cleave DEVD sand VEID peptides; when associated with 232-H--E-234.
In esCasp-7 V3 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with 230-V--V-234.
In esCasp-7 V3 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with C-276. In esCasp-7 V4 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with D-276.
In esCasp-7 V4 mutant; promotes specificity toward alternate peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when associated with 230-V--V-234.
In mutant II; prevents cleavage of loop L2 region; retains significant thiol protease activity.
In mutant III; prevents cleavage of loop L2 region; abolished thiol protease activity.
In mutant IV; prevents cleavage of loop L2 region; retains significant thiol protease activity.
Mimics phosphorylation; does not affect thiol protease activity.
Mimics phosphorylation; leading to inactivate thiol protease activity.
Reduced cleavage and activation by initiator caspases. Abolished cleavage and activation by initiator caspases; when associated with A-198.
Reduced thiol protease catalytic efficiency.
Strongly reduced cleavage and activation by initiator caspases. Abolished cleavage and activation by initiator caspases; when associated with A-206. In P7-D2A mutant; abolished cleavage and activation, leading to decreased but mesureable activity; when associated with A-23.
Strongly reduced thiol protease activity.
Strongly reduced thiol protease catalytic efficiency.
In POF13; decreased function in DNA repair as suggested by the persistence of gamma-H2AX foci following cell treatment with etoposide.
In POF13; unknown pathological significance.
Probable cation-transporting ATPase 13A4
In WS1; associated with H-271 in one family; unknown pathological significance.
In WS1; associated with K-273 in one family.
In WS1; associated with meningomyelocele.
In WS1; originally classified as Waardenburg syndrome type 2.
In WS1; results in decreased transcriptional activation of MITF; no effect on localization to nucleus; no effect on interaction with SOX10.
In ZKS; results in decreased secretion of WNT3A and WNT5A; decreased activation of WNT signaling.
In HPMRS6; may diminish protein expression and/or stability; decreases cell surface expression of GPI-anchored proteins, including CD55 and CD59, in skin fibroblasts from affected individual.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit Y
Abolishes lowering of temperature threshold for activation in response to reactive oxygen species.
Decreased channel activity in response to ADP-ribose.
Expected to abolish the initially proposed hydrolase activity. Does not abolish channel activity in response to ADP-ribose.
No effect on channel activity; when associated with G-1407.
No effect on channel activity; when associated with Q-1400.
No significant effect on channel activity; when associated with A-302.
No significant effect on channel activity; when associated with A-358.
Prevents fast inactivation of the channel.
Strongly increased residual channel activity after exposure to pH 5.5.
Strongly reduces channel activity at ph 7.3. Increased residual channel activity after exposure to pH 5.5.
Transient receptor potential cation channel subfamily M member 2
Impairs interaction with CDC42 and reduces CDC42-induced actin assembly.
Impairs interaction with WASL and reduces CDC42-induced actin assembly.
Inverted topology. No effect on activity.
No effect on topology. Increased Km for corticosterone.
Predominantly inverted topology. No effect on activity.
No effect on catalytic activity when DTT is used as an electron donor; when associated with A-90. Loss of catalytic activity when P4HB is used as an electron donor; when associated with A-90.
No effect on catalytic activity when DTT is used as an electron donor; when associated with A-95. Loss of catalytic activity when P4HB is used as an electron donor; when associated with A-95.
Slightly decrease in activity. Significant increased activity; when associated with A-130.
Small increase in activity. Significant increased activity; when associated with A-130.
Some decrease in P4HB-binding. Efficient homodimerization with wild-type protein, but loss of homodimerization with A-396 mutated protein. Loss of catalytic activity when DTT or P4HB are used as an electron donor; when associated with A-393.
Some decrease in P4HB-binding. Efficient homodimerization with wild-type protein. Loss of catalytic activity when DTT or P4HB are used as an electron donor; when associated with A-396.
Strong decrease in P4HB-binding. Efficient homodimerization with both wild-type and A-390 mutated protein.
RNA 3'-terminal phosphate cyclase-like protein
Eukaryotic translation initiation factor 1
(S/T)X(I/L)P motif 3; required for interaction with MAPRE1
Loss of interaction with MAPRE1 and significantly reduced localization to microtubule plus ends. Loss of interaction with MAPRE1 and localization to microtubule plus ends; when associated with 486-A-A-487 and 818-A-A-819.
No decrease in localization to microtubule plus ends. Loss of interaction with MAPRE1 and localization to microtubule plus ends; when associated with 486-A-A-487 and 928-A-A-929.
No decrease in localization to microtubule plus ends. Loss of interaction with MAPRE1 and localization to microtubule plus ends; when associated with 818-A-A-819 and 928-A-A-929.
Decreases interaction with YWHAQ, cellular signaling pathway activation and cytokine secretion.
No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 164-A--A-170 and 335-A--A-338.
No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 164-A--A-170 and 423-A--A-426.
No effect on nuclear translocation upon induction by MDP. Abolishes nuclear translocation upon induction by MDP and slightly decreases NOD2-induced AP-1 and NF-kappaB activation and IL6 secretion; when associated with 335-A--A-338 and 423-A--A-426.
Diphosphoinositol polyphosphate phosphohydrolase 3-beta
PXXP motif; required for interaction with CTTN
Zinc finger and BTB domain-containing protein 14
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3
Mediator of RNA polymerase II transcription subunit 24
Homeobox and leucine zipper protein Homez
Abolised protein acetyltransferase activity.
Catalytically dead mutant; abolished acyltransferase activity; when associated with A-575.
Catalytically dead mutant; abolished acyltransferase activity; when associated with A-615.
Mimics acetylation; reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with A-307 and A-735.
Reduced ability to acetylate and inhibit PPARGC1A.
Reduced histone succinylation without affecting histone acetylation. Reduced gene expression.
Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with A-307 and Q-549.
Slightly reduced ability to acetylate and inhibit PPARGC1A. Strongly reduced ability to acetylate and inhibit PPARGC1A; when associated with Q-549 and A-735.
Sodium-dependent phosphate transport protein 3
Decreases binding to MTRR; when associated with E-963.
Decreases binding to MTRR; when associated with N-1071.
Serine/threonine-protein phosphatase 6 regulatory subunit 1
Abolihsed ability to degrade HIV-1 mRNAs.
Abolished ability to interact with ubiquitin.
Abolishes LPIAT activity. No effect on LPGAT activity.
EF-hand calcium-binding domain-containing protein 4A
Elongation of very long chain fatty acids protein 4
Pleckstrin homology domain-containing family A member 7
Does not affect protein homooligomerization. Loss of protein homooligomerization; when associated with S-1315 and S-1316.
Does not affect protein homooligomerization. Loss of protein homooligomerization; when associated with S-1315 and S-1319.
Does not affect the proteolytic processing.
Loss of bromide oxidation. Loss of tubulogenesis. Does not induce angiogenesis.
Loss of peroxidase activity. Does not affect oligomerization. Loss of peroxidase activity; when associated with E-823. Does not support the formation of collagen IV cross-links; when associated with W-823. Reduces the proteolytic processing; when associated with W-823. Loss of collagen IV cross-link; when associated with W-823.
Loss of peroxidase activity. Does not affect oligomerization. Loss of peroxidase activity; when associated with E-826. Does not support the formation of collagen IV cross-links; when associated with E-826. Reduces the proteolytic processing; when associated with E-826. Loss of collagen IV cross-link; when associated with E-826.
Loss of protein homooligomerization. Loss of protein homooligomerization; when associated with S-1315. Does not affect peroxidase activity; when associated with S-1315. Retains the ability to support the collagen IV cross-links; when associated with S-1315. Slightly reduces proteolysis; when associated with S-1315.
Loss of protein homooligomerization. Loss of protein homooligomerization; when associated with S-1316 and S-1319. Loss of protein homooligomerization; when associated with S-736. Does not affect peroxydase activity; when associated with S-736. Affects cell surface location; when associated with S-736. Slightly reduces proteolysis; when associated with S-736.
Loss of proteolytic cleavage. Decreases the formation of sulfilimine cross-links in collagen IV. Reduces the proteolytic processing. Affects collagen IV cross-linking.
Abolishes enzyme activity and ability to bind tRNA.
Found in familial late-onset hereditary ataxia; unknown pathological significance.
tRNA-splicing endonuclease subunit Sen54
Ral guanine nucleotide dissociation stimulator
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
Mildly reduces kinase activity. Does not abolish autophosphorylation on tyrosine residues.
In isoform 2, isoform 3, isoform 5 and isoform 8.
In isoform 5, isoform 6, isoform 7, isoform 8, isoform 9 and isoform 10.
CKLF-like MARVEL transmembrane domain-containing protein 7
In CSNB2A; increases the number of mutant channels open at physiologic membrane potential and allows for persistent Ca(2+) entry due to reduced channel inactivation resulting in a gain-of-function defect.
In CSNB2A; unknown pathological significance.
Voltage-dependent L-type calcium channel subunit alpha-1F
FYVE, RhoGEF and PH domain-containing protein 2
In CESD; significant loss of enzyme activity.
Lysosomal acid lipase/cholesteryl ester hydrolase
ELKS/Rab6-interacting/CAST family member 1
In diatrophic dysplasia; broad bone-platyspondylic variant.
In DEE53; decreased inositol phosphate phosphatase activity.
In PARK20; impairs the phosphatase activity of the enzyme toward phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate.
In PARK20; unknown pathological significance; the patient also carries a heterozygous PINK1 truncating mutation.
Likely benign variant; no effect on inositol phosphate phosphatase activity.
Leucine-rich repeat-containing protein 36
E3 ubiquitin-protein ligase pellino homolog 1
Loss of ability to ubiquitinate RIPK3. Loss of interaction with RIPK1, IRAK1 and RIPK3.
Loss of ability to ubiquitinate RIPK3. No loss of interaction with RIPK3.
Calcium-binding mitochondrial carrier protein SCaMC-2
In SEDT; loss of interaction with ENO1, PITX1 and SF1.
In SEDT; mild form; loss of interaction with ENO1, PITX1 and SF1.
Trafficking protein particle complex subunit 2
Trafficking protein particle complex subunit 2B
2-iminobutanoate/2-iminopropanoate deaminase
In SRTD18; patient cells show reduced amount of IFT43 protein and do not have cilia.
Intraflagellar transport protein 43 homolog
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform
Mitochondrial 2-oxoglutarate/malate carrier protein
Abolishes heterodimerization with TCF3 isoform E47; no effect on nuclear localization.
Does not affect DNA-binding activity or transcription activation.
Found in a sporadic case of optic nerve hypoplasia; unknown pathological significance; does not affect DNA-binding activity but reduces transcription activation.
Found in patients with bilateral optic nerve hypoplasia; unknown pathological significance; abolishes heterodimerization with TCF3 E47 isoform; reduces DNA-binding ability and abolishes transcriptional activation; no effect on nuclear localization.
In PHPVAR; loss of function; polypeptide is stable, but does not bind DNA or activate transcription; does not restore retinal ganglion cell development in retinal explants from a mouse Atoh7 null mutant; abolishes heterodimerization with TCF3 E47 isoform; reduces DNA-binding ability and abolishes transcriptional activation; no effect on nuclear localization.
In PHPVAR; unknown pathological significance.
Loss of DNA-binding activity; loss of ability to restore retinal ganglion cell development in retinal explants from a mouse Atoh7 null mutant.
Impairs the reductase activity toward cytochrome c in the presence of NADPH; when associated with T-111 and T-137. Impairs the reductase activity toward oxidized collagen; when associated with T-111 and T-137.
Impairs the reductase activity toward cytochrome c in the presence of NADPH; when associated with T-111 and T-149. Impairs the reductase activity toward oxidized collagen; when associated with T-111 and T-149.
Impairs the reductase activity toward cytochrome c in the presence of NADPH; when associated with T-137 and T-149. Impairs the reductase activity toward oxidized collagen; when associated with T-137 and T-149.
Impairs the reductase activity toward cytochrome c independently of the electron donnor. Decreases the reductase activity toward methemoglobin. Decreases the reductase activity toward oxidized collagen.
Inter-alpha-trypsin inhibitor light chain
O-linked (Xyl...) (chondroitin sulfate) serine
Has not effect on protein abundance; does not affect localization to Golgi apparatus; does not affect function in regulation of RAS-MAPK signaling.
In GLM; increased Ras signaling; decreased ubiquitination of Ras.
In NS10 and GLM; increased RAS-MAPK signaling; decreased ubiquitination of Ras; decreased stability; no effect on localization to Golgi apparatus.
In NS10 and SWNTS2; increased RAS-MAPK signaling; decreased stability; no effect on localization to Golgi apparatus.
In NS10; increased RAS-MAPK signaling; decreased stability; no effect on localization to Golgi apparatus.
In NS10; unknown pathological significance.
In NS2; decreased ubiquitination of Ras.
In NS2; unknown pathological significance.
In NS2; unknown pathological significance; no effect on RAS-MAPK signaling; decreased localization to Golgi apparatus; no effect on stability.
In NS2; unknown pathological significance; no effect on RAS-MAPK signaling; decreased stability.
In NS2; unknown pathological significance; no effect on RAS-MAPK signaling; no effect on stability.
In NS2; unknown pathological significance; no effect on RAS-MAPK signaling; strongly decreased stability.
In NS2; unknown pathological significance; when associated with W-170.
In SWNTS2; decreased interaction with CUL3; impaired subcellular location; decreased ubiquitination of Ras.
In SWNTS2; increased RAS-MAPK signaling.
In SWNTS2; increased Ras signaling; decreased binding to Ras.
In SWNTS2; increased Ras signaling; decreased interaction with CUL3; impaired subcellular location.
In SWNTS2; increased Ras signaling; decreased interaction with CUL3; impaired subcellular location; impaired subcellular location.
In SWNTS2; increased Ras signaling; impaired subcellular location.
In SWNTS2; unknown pathological significance.
In SWNTS2; unknown pathological significance; no effect on stability.
In SWNTS2; unknown pathological significance; no effect on stability; no effect on localization to Golgi apparatus.
In SWNTS2; unknown pathological significance; somatic mutation.
Leucine-zipper-like transcriptional regulator 1
Loss of inhibitory activity towards trypsin.
No effect on inhibitory activity towards trypsin.
Reduces inhibitory activity towards trypsin.
Sodium/potassium-transporting ATPase subunit beta-1-interacting protein
Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 4
In SIOD; abolishes annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage.
In SIOD; impairs without abolishing annealing helicase activity; no effect on specific binding to fork DNA; no effect on recruitment to sites of DNA damage.
Loss of interaction with RPA2 and impaired recruitment by the RPA complex to sites of DNA damage.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1
Abolishes interaction with UIMC1 and SHMT2.
Abolishes localization to sites of DNA damage and interaction with ABRAXAS2; UIMC1; SHMT2; BABAM2 and BABAM1; when associated with R-23.
Abolishes localization to sites of DNA damage and interaction with ABRAXAS2; UIMC1; SHMT2; BARAM2 and BABAM1; when associated with R-27.
Abolishes metalloprotease activity and function in DNA repair.
Putative methyl-CpG-binding domain protein 3-like 4
Tuberoinfundibular peptide of 39 residues
Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-109 and E-111.
Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-95 and E-109.
Alters interaction with MAPRE1 and association with microtubule growing ends; when associated with E-95 and E-111.
Loss of interaction with MAPRE1 and association with microtubule growing ends.
(Microbial infection) Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-50); by Vibrio toxins RtxA and VgrG1
(Microbial infection) Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-270); by Vibrio toxins RtxA and VgrG1
Actin, cytoplasmic 2, N-terminally processed
Found in a patient with isolated coloboma; decreased incorporation into F-actin; decreased interaction with cofilin; loss of interaction with TWF1, CAPZB and profilin.
In DFNA20; unknown pathological significance.
N-acetylglutamate; in Actin, cytoplasmic 2, N-terminally processed; partial
Decreased constitutive signaling activity.
Increased constitutive signaling activity.
Mitochondrial import inner membrane translocase subunit Tim17-A
20-fold decrease in Km for ATP and 3-fold decrease in Km for fructose-6 phsphate.
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
In MC1DN6; loss of catalytic activity; no change in Km value for ubiquinone-1.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
Reduces interaction with the C9ORF72-SMCR8 complex; when associated with R-445. No effect on interaction with SMCR8.
Reduces interaction with the C9ORF72-SMCR8 complex; when associated with R-449. No effect on interaction with SMCR8.
Decreased interaction with CSNK1A1 and loss of function in keratin cytoskeleton organization.
No effect on interaction with CSNK1A1 and function in keratin cytoskeleton organization.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Loss of interaction with WWOX; when associated with A-59.
Loss of interaction with WWOX; when associated with A-64.
Abolishes binding to MEFV. Cytoplasmic filaments are finer with fewer branches.
In PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; increased induction of MEFV in response to retroviral infection.
In PAPAS; severely reduced binding with PTPN12; markedly increased binding to MEFV; accentuates IL1B secretion; no effect on filament formation; increased induction of MEFV in response to retroviral infection.
Proline-serine-threonine phosphatase-interacting protein 1
Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity.
Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity.
Decreased protein stability. Decreased transcriptional activity.
Decreased protein stability. No effect on transcriptional activity.
In ASGD3 and RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In ASGD3 and RIEG3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In ASGD3; no change in protein abundance; changed post-translational phosphorylation; changed protein structure; decreased location at the nucleus; novel location at the cytoplasm; increased protein aggregation, aggregation do not correspond to microtubule-dependent inclusion bodies; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity.
In ASGD3; no effect on protein abundance; increased protein stability; no effect on nuclear location; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3 and ASGD3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3 and ASGD3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity.
In RIEG3; decreased protein abundance; decreased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity.
In RIEG3; hypomorphic mutation; decreased protein abundance; decreased protein stability; changed post-translational phosphorylation; decreased location at the nucleus; novel location at the cytoplasm; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; no change in location at the nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; no effect on protein abundance; changed post-translational phosphorylation; novel location at aggresome, aggregation correspond to microtubule-dependent inclusion bodies; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; no effect on protein abundance; increased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity.
In RIEG3; no effect on protein abundance; no effect on protein stability; no effect on location at nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity.
In RIEG3; unknown pathological significance.
No effect on protein abundance; no effect on protein stability; no effect on nuclear location; no effect on transcription regulatory region DNA binding; no effect on sequence-specific DNA binding transcription factor activity.
No effect on protein stability. No effect on transcriptional activity.
Does not inhibit interaction with MAP3K5. Does not reduce GSK3B-induced beta-catenin transcription activity, TNF-alpha-induced apoptosis, ARF6-mediated TLR4-TIRAP-MyD88 signaling inhibition, Ras and NF-kappa-B activities and tumor development. Does not suppress tumor development; when associated with A-728.
Does not reduce interaction with 14-3-3 proteins.
Inhibits phosphorylation and TNF-alpha-induced MAP3K5 dephosphorylation. Reduces interaction with 14-3-3 proteins, AKT1, a regulatory p85 subunit, MAP3K5, RIPK1, TRAF2 and TNF-alpha-induced MAP3K5-JNK signaling and apoptosis. Reduces RAS activity. Does not reduce GSK3B-induced beta catenin-mediated transcription activity. Does not reduce NF-kappa-B activity, cell invasion, epithelial-to-mesenchymal transition (EMT) and tumor development. Does not suppress tumor development; when associated with R-413.
Reduces interaction with KDR/VEGFR2. Does not inhibit interaction with MAP3K5.
Reduces interaction with a regulatory p85 subunit of the PI3K complex. Inhibits MAP3K5 active form increase, AKT1 active form decrease, PI3K-p85 complex activity inhibition and TNF-induced apoptosis.
Significantly reduces interaction with MAP3K5. Does not reduce interaction with KDR/VEGFR2.
Affects its ability to cleave 'K63'-linked ubiquitin.
In CTRCT1; decreased gap junction channel activity.
In CTRCT1; nuclear progressive cataract.
In CTRCT1; severely decreased gap junction channel activity; does not localize to the cell membrane.
In CTRCT1; unknown pathological significance.
In CTRCT1; unknown pathological significance; abolishes localization to the plasma membrane and function.
In CTRCT1; zonular pulverulent and nuclear progressive cataract.
Likely benign variant; does not affect gap junctions formation and gap junctional currents.
Gly-Pro-Asn (GPN)-loop; involved in dimer interface
Abolishes association with the mitotic spindle.
Abolishes association with the mitotic spindle. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2015 and A-2055.
Abolishes association with the mitotic spindle. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2055 and A-2087.
Absence of cell membrane association even in anaphase. Increased localization at spindle poles and chromosome congression defects. Does not localize to the cortex in either metaphase or anaphase. Increased randomization of spindle orientation.
Increases localization at the spindle poles. Decreases localization at the cell cortex.
Increases premature accumulation at the cell membrane of the polar cortical region in prophase and metaphase. Reduces association with the mitotic spindle. Increased randomization of spindle orientation. Increases premature accumulation at the cell cortex during metaphase; when associated with A-2015 and A-2087.
Cation channel sperm-associated targeting subunit tau
In SPGF68; unknown pathological significance.
Found in a family with intellectual disability; unknown pathological significance.
Submaxillary gland androgen-regulated protein 3B
Defective in mediating calcium response.
Found in patients with chronic lymphocytic leukemia; unknown pathological significance; results in resistance to ibrutinib therapy; results in a protein that is reversibly inhibited by ibrutinib; disrupts the covalent binding between the enzyme and ibrutinib.
In XLA; loss of phosphorylation of GTF2I.
In XLA; mild; interferes with substrate binding and/or domain interactions.
In XLA; mild; interferes with substrate binding.
In XLA; moderate; interferes with substrate binding.
In XLA; no effect on phosphorylation of GTF2I.
In XLA; severe; prevents activation due to absence of contact between the catalytic loop and the regulatory phosphorylated residue.
In a lung large cell carcinoma sample; somatic mutation; requires 2 nucleotide substitutions.
In isoform 3, isoform 4, isoform 5 and isoform 6.
Rap1 GTPase-GDP dissociation stimulator 1
In MVA3; loss of protein expression; impairment of spindle assembly checkpoint.
In OOMD9; decreased protein level in patient cells.
In OOMD9; unknown pathological significance.
Basic leucine zipper transcriptional factor ATF-like 3
Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase 3
In CTRCT6; reduced protein stability and reduced ability to stimulate cell migration in absence of its ephrin ligand.
In CTRCT6; retained in the cytoplasm and constitutively active it alters EPHA2 signaling.
In a gastric adenocarcinoma sample; somatic mutation.
Increases serum-induced chemotaxis. Loss of EFNA1-dependent regulation of cell migration.
Loss of serum-induced phosphorylation by PKB. Loss of serum-induced chemotaxis.
Phosphoserine; by PKB/AKT1, RPS6KA1, RPS6KA3 AND PKA
Significantly reduced response to EFNA1.
LysM and putative peptidoglycan-binding domain-containing protein 1
Converts geranyl-geranylation to farnesylation. No effect on membrane localization. Confers resistance to GGTI-induced pancreatic cancer cell apoptosis, but not to GGTI-dependent inhibition of anchorage-independent proliferation.
Impaired abscission, the last step of cytokinesis, as shown by the accumulation of bridged cells. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23.
Impaired abscission, the last step of cytokinesis. No effect on cytokinesis; when associated with V-23.
Impaired cytokinesis, as shown by increased number of binucleate cells. Impaired cytokinesis; when associated with 1-M--S-11 or N-49. No effect on cytokinesis; when associated with R-38, W-48 or E-49. No effect on interaction with EXOC2 and EXOC8. Decreased interaction with EXOC2 and EXOC8; when associated with R-38 or W-48.
Loss of geranylgeranylation and membrane localization.
No effect on cytokinesis. Impaired cytokinesis, as shown by increased number of binucleate cells; when associated with V-23.
No effect on cytokinesis. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23.
Reduces the binding affinity to EXOC2 effector.
Does not affect subcellular localization. Abolishes lyase activity. Does not affect subcellular localization, abolishes lyase activity, does not affect oligomerisation and does not bind TTP; when associated with S-455.
Does not affect subcellular localization. Abolishes lyase activity. Does not affect subcellular localization, abolishes lyase activity, does not affect oligomerisation and does not bind TTP; when associated with S-456.
Ubiquitin carboxyl-terminal hydrolase 17-like protein 1
T-complex protein 1 subunit eta, N-terminally processed
In a lung neuroendocrine carcinoma sample; somatic mutation.
In a lung small cell carcinoma sample; somatic mutation.
Kinase-dead. Loss of autophosphorylation.
Partial loss of phosphorylation and loss of interaction with SH2-containing proteins.
Oxidative stress-induced growth inhibitor 2
Cilia- and flagella-associated protein 44
In PFIC8; unknown pathological significance.
T-cell leukemia translocation-altered gene protein
In GALAC4; loss of protein accumulation.
In GALAC4; unknown pathological significance; decreased protein stability.
Cyclin-dependent kinase 5 activator 1, p25
Cyclin-dependent kinase 5 activator 1, p35
In L-3A mutant; abolished recognition and ubiquitination by the CRL2(FEM1B) complex.
In L-3R mutant; abolished recognition and ubiquitination by the CRL2(FEM1B) complex, while promoting recognition and ubiquitination by the CRL2(FEM1B) complex.
Leucine-rich repeat transmembrane protein FLRT1
Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)
In isoform 5, isoform 6, isoform 7 and isoform 8.
Growth hormone-inducible transmembrane protein
In PTHS; also expressed in the nucleus with a pattern indistinguishable from the wild-type; does not have a major impact on homodimer formation; affects transcriptional activity in a context-dependent manner.
In PTHS; loss of function; also expressed in the nucleus with a pattern indistinguishable from the wild-type; does not have a major impact on homodimer formation; affects transcriptional activity in a context-dependent manner.
In PTHS; loss of function; mislocalized to small spherical punctae that are dispersed throughout the nucleus; can attenuate homo- and heterodimer formation; affects transcriptional activity in a context-dependent manner.
In PTHS; mislocalized to small spherical punctae that are dispersed throughout the nucleus; can attenuate homo- and heterodimer formation; affects transcriptional activity in a context-dependent manner.
In isoform 13, isoform C- and isoform C-delta.
In isoform A-, isoform B-delta, isoform B+delta and isoform C-delta.
In isoform B+delta, isoform SEF2-1A, isoform SEF2-1D, isoform 11 and isoform 13.
Probable disease-associated variant found in a family with symmetrical acral keratoderma.
In AMYL8; also found in a family with amyloid polyneuropathy-nephropathy Iowa.
In AMYL8; plasma level of HDL and apoA-I protein were significantly lower in the patient.
In AMYL8; unknown pathological significance.
In Boston; no evidence of association with premature coronary heart disease; associated with decreased levels of HDL cholesterol; associated with decreased serum cellular cholesterol efflux; associated with decreased lecithin-cholesterol acyltransferase (LCAT) activity.
In HDL deficiency; with periorbital xanthelasmas; decreased protein abundance.
In Milano; no evidence of association with premature vascular disease; associated with decreased HDL levels and moderate increase in triglycerides; allows the formation of disulfide-linked homodimers via the introduced cysteine; assembles properly in HDL; alters protein structure; has no tendency to form fibrils and aggregates.
In Oita; 60% of normal apoA-I and normal HDL cholesterol levels; rapidly cleared from plasma.
With 1 methionine sulfoxide, oxidation at Met-110.
With 1 methionine sulfoxide, oxidation at Met-136.
With 2 methionine sulfoxides, oxidation at Met-110 and Met-136.
10-fold reduction in receptor activation.
10-fold reduction in receptor activation. Strongly reduced localization to the cell membrane.
500-fold decrease of IC(50) for GSK682753A. No effect on oxysterol agonist-binding and receptor activation.
Abolishes localization to the cell membrane without affecting protein expression levels.
In an acute myeloid leukemia sample; somatic mutation.
Increased receptor activation. Strongly reduced localization to the cell membrane.
Loss of receptor activation without affecting oxysterol agonist-binding.
Reduced localization to the cell membrane and reduced receptor function, without affecting oxysterol agonist-binding.
Reduced localization to the cell membrane and reduced receptor function.
Reduced localization to the cell membrane and reduced receptor function. Reduced oxysterol agonist-binding.
Slight decrease in oxysterol agonist-binding and receptor activation.
Strong decrease in oxysterol agonist-binding and receptor activation.
Strongly reduced localization to the cell membrane and reduced protein expression levels.
Strongly reduced localization to the cell membrane.
Cytochrome b-c1 complex subunit 6, mitochondrial
Calcium and integrin-binding family member 3
Dominant-negative mutant. Defective in integrin-binding and in ternary complex formation with integrin and FGFR1. No effect on heparin- and FGFR1-binding. Defective in inducing FGF1 signaling, cell proliferation and cell migration. Defective in inducing angiogenesis, and suppression of angiogenesis in different in vitro and in vivo angiogenesis models.
Loss of CSNK2A-, CSNK2B- and LRRC59-binding. Reduced integrin-binding; when associated with E-134. Defective in integrin-, heparin- and FGFR1-binding, and defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with E-128; E-133 and E-134.
Loss of nuclear import leading to loss of phosphorylation by PKC/PRKCD.
No effect on integrin- and heparin-binding, loss of FGFR1-binding, defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with A-102 and A-110.
No effect on integrin-binding. No effect on integrin- and heparin-binding, loss of FGFR1-binding, defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with A-102 and A-109.
No effect on integrin-binding. No effect on integrin- and heparin-binding, loss of FGFR1-binding, defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with A-109 and A-110.
Reduced integrin-binding; when associated with E-127. Defective in integrin-, heparin- and FGFR1-binding, and defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with E-127; E-133 and E-134.
Reduced integrin-binding; when associated with E-128. Defective in integrin-, heparin- and FGFR1-binding, and defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with E-128; E-133 and E-134.
Reduced integrin-binding; when associated with E-133. Defective in integrin-, heparin- and FGFR1-binding, and defective in inducing FGF1 signaling, cell proliferation and cell migration; when associated with E-127; E-128 and E-133.
Loss of DNA (TRE) binding. Reduces the corepressor activity towards THRB.
Nuclear receptor subfamily 2 group F member 6
Ankyrin repeat domain-containing protein 7
Tumor protein p53-inducible nuclear protein 2
Does not inhibit insulin-stimulated SLC2A4/GLUT4 translocation.
Inhibits insulin-stimulated AKT2-induced phosphorylation, SLC2A4/GLUT4 translocation to the cell surface and GSV-PM fusion.
Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-76 and A-78.
Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-76 and A-84.
Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-78 and A-84.
Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-76; A-78 and A-84.
Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-26; A-76; A-78 and A-84.
Abolishes sumoylation. No change in nuclear location. Increases transcriptional activity and cell cycle progression. Abolishes sumoylation; when associated with R-217.
No change in sumoylation. Abolishes sumoylation; when associated with R-67.
In allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction.
In allele A3H-Var; haplotype 2; allele presenting a higher expression and which is more effective in retrotransposons and HIV-1 restriction; increases protein stability.
Reduces the ability to inhibit the retrotransposition of LINE-1 elements.
Class E basic helix-loop-helix protein 23
Chromosome transmission fidelity protein 8 homolog
39S ribosomal protein L15, mitochondrial
Abolishes serine protease activity. Does not promote FAM20C kinase activity.
In SEDKF; due to a nucleotide substitution that creates a dominant splice donor site in exon 9; two different type of transcripts are produced, a major non-functional alternatively spliced transcript with a 41-bp deletion of exon 9, loss of S-414 in the catalytic triad and premature truncation and a normally spliced transcript with variant G-365; the transcript with G-365 produces a catalytically active protein but is the less abundant.
Membrane-bound transcription factor site-1 protease
Frequency <0.004; may play a role in breast cancer susceptibility.
Found in a patient with Leber congenital amaurosis.
In a head & Neck squamous cell carcinoma sample; somatic mutation.
Found in a patient with progressive myoclonus epilepsy; unknown pathological significance.
In SCAR16; inhibits ubiquitin ligase activity and autoubiquitination.
In SCAR16; reduces protein level; does not reduce ubiquitin ligase activity and autoubiquitination.
In SCAR16; reduces protein level; reduces ubiquitin ligase activity; does not change autoubiquitination.
Loss of ability to ubiquitinate FOXP3 and SIRT6.
Loss of interaction with FOXP3 and its ability to ubiquitinate FOXP3. Loss of interaction with SMAD3, HSPA8, HSP90AA1 and HSP90AB1.
Abolishes glycosyltransferase activity and ability to rescue left-right patterning defects induced by galnt11 knockdown in X.tropicalis.
Polypeptide N-acetylgalactosaminyltransferase 11
Cytochrome c oxidase assembly protein COX14
cAMP-dependent protein kinase inhibitor beta
Pre-B-cell leukemia transcription factor 2
RUN and FYVE domain-containing protein 4
Voltage-dependent calcium channel gamma-8 subunit
Serine/threonine-protein phosphatase CPPED1
Acyl-CoA-binding domain-containing protein 4
Complete loss of activity after pulsatile shear stress.
Histone acetyltransferase type B catalytic subunit
No loss of activity after pulsatile shear stress.
In PSORS15; results in decreased TLR3 targeting to the endosomes indicating impaired function.
In PSORS15; results in decreased protein levels.
Testis, prostate and placenta-expressed protein
LETM1 domain-containing protein LETM2, mitochondrial
SH3 domain-binding glutamic acid-rich-like protein 2
Succinate dehydrogenase cytochrome b560 subunit, mitochondrial
Microtubule-associated proteins 1A/1B light chain 3 beta 2
Phosphatidylethanolamine amidated glycine; alternate
Phosphatidylserine amidated glycine; alternate
Low affinity immunoglobulin epsilon Fc receptor membrane-bound form
Low affinity immunoglobulin epsilon Fc receptor soluble form
Does not affect localization to peroxisomes.
In S3E mutant; Abolished localization to peroxisomes.
Translocon-associated protein subunit gamma
Abolishes N-alpha-acetyltransferase activity.
Decreased acetylation; when associated with 34-A-A-37.
Decreased acetylation; when associated with A-140.
Reduces N-alpha-acetyltransferase activity.
Restores the acetylation activity of the NatA complex.
Strongly decreased N-alpha-acetyltransferase activity.
Strongly decreased N-alpha-acetyltransferase activity. Impaired sister chromatid cohesion during mitosis.
Gamma-aminobutyric acid receptor subunit theta
Alters localization to the autophagosome; when associated with Leu-244.
Alters localization to the autophagosome; when associated with Leu-248.
Alters localization to the autophagosome; when associated with Leu-264.
Alters localization to the autophagosome; when associated with Leu-268.
Localizes to the Golgi instead of the endoplasmic reticulum.
In ADTKD5; decreases in protein stability; partly confers novel Golgi subcellular location.
Probable disease-associated variant found in a family with hypogammaglobulinemia; decreased function in cotranslational protein targeting to endoplasmic reticulum.
Protein transport protein Sec61 subunit alpha isoform 1
Reduces cotranslational translocation of APLN precursor/preproapelin.
Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-603 and E-641.
Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-603 and E-703.
Decreases interaction with SYNE2. Disrupts interaction with SYNE2; when associated with E-641 and E-703.
Decreases stability of the SUN2:SYNE2/KASH2 complex under tensile forces and inhibits force transmission through the complex.
Disrupts interaction with SYNE2, impairs localization to the nuclear envelope.
POU domain, class 6, transcription factor 2
N-acetylthreonine; partial; in Histone H1.0, N-terminally processed
Rho guanine nucleotide exchange factor 11
Abolishes protease activity. Stabilizes the protein.
Sarcoplasmic reticulum histidine-rich calcium-binding protein
Does not affect the cellular localization and the biological activity.
In HTX2; complete loss of activity; abnormal cell surface localization.
Abolishes prenylation. Predominantly cysolic with little plasma membrane-associated expression. Reduces cell migration by affecting filopodia formation.
No effect on subcellular location. Low protein abundance, suggesting that stability is affected.
Abolishes oxidative stress-induced phosphorylation and RAN binding. Impaired nuclear export and enhanced antiapoptotic activity against ROS-dependent apoptosis induction. Impaired interaction with PTPN11. No dephosphorylation by PTPN11.
Abolishes telomerase catalytic activity.
About 75% reduction in telomerase activity, about 50% reduction in repeat extension rate and 5.2-fold increase in nucleotide incorporation fidelity. Little further reduction in activity and 13.5-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity.
About 80% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. Little effect on repeat addition processivity, nor on TR interaction nor on protein levels.
About 85% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction.
About 90% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction.
Completely abolishes telomerase-mediated primer extension and reduced binding to short telomeric primers. Complete loss of catalytic activity but no further loss of binding to telomeric primers; when associated with 137-A--A-141.
Defective in high-affinity TERC interactions.
In AA; abolishes telomerase catalytic activity but no effect on binding to TERC.
In AA; associated with susceptibility to acute myeloid leukemia.
In AA; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC.
In AA; very severe; no effect on telomerase catalytic activity but shortened telomeres.
In DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC.
In DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC.
In DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC.
In DKCB4; 50% reduction in telomerase activity.
In DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC.
In DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity.
In DKCB4; the mutant protein has 13% residual activity.
In PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres.
In PFBMFT1, AA and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity.
In PFBMFT1; associated with Ile-791 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity; this mutation causes most if not all of the functional defects.
In PFBMFT1; associated with Met-867 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity.
In PFBMFT1; impaired telomerase activity.
In PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity.
In PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity.
In PFBMFT1; unknown pathological significance; impaired telomerase activity.
Increased incidence in sporadic acute myeloid leukemia.
Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers.
Moderate reduction in telomerase activity, no change in repeat extension rate nor on nucleotide incorporation fidelity. Little further reduction in activity but 13.5-fold increase in nucleotide incorporation fidelity; when associated with M-867.
Phosphotyrosine; by SRC-type Tyr-kinases
Reduced catalytic activity and repeat addition processivity. Complete loss of catalytic activity but no loss of binding to telomeric primers; when associated with 930-A--A-934.
Severe reduction in telomerase activity, about 50% reduction in repeat extension rate and 2.2-fold increase in nucleotide incorporation fidelity. No further reduction in activity but 2.8-fold increase in nucleotide incorporation fidelity; when associated with Y-866.
Centriole and centriolar satellite protein OFD1
In JBTS10; unknown pathological significance.
Loss of phosphorylation by PKA. Loss of cAMP-dependent interaction with TBC1D31. Loss of ubiquitin-mediated proteasomal degradation. Loss of function in cilium assembly. Dominant negative effect.
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit C
Zinc finger and SCAN domain-containing protein 5B
Regains racemase activity, catalyzing the conversion of trans-3-hydroxy-L-proline to cis-3-hydroxy-D-proline. Also catalyzes racemization of L-proline to D-proline, albeit at a very low level. Has lost its original dehydratase activity.
Does not affect subcellular location, suggesting this protein is not prenylated.
Rho-related BTB domain-containing protein 3
Eukaryotic translation initiation factor 3 subunit C-like protein
PiggyBac transposable element-derived protein 4
Calcium-activated potassium channel subunit beta-1
Has a protective effect against diastolic hypertension.
Double-stranded RNA-binding protein Staufen homolog 1
Affects the glycopeptide specificity and abolishes ability to glycosylate Muc1, Muc2 and Muc5AC.
Polypeptide N-acetylgalactosaminyltransferase 4
Absent from nuclear speckle; no change in transcriptional activity.
POU domain, class 4, transcription factor 2
Polypeptide N-acetylgalactosaminyltransferase 5
Guanine nucleotide exchange factor for Rab-3A
In ATS1; found on the same allele as variant Glu-1211.
In ATS1; found on the same allele as variant Val-953.
In ATS1; juvenile type; unknown pathological significance.
In ATS1; presenting with dot-and-fleck retinopathy.
S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1549)
S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1667)
dolichyl-phosphate-mannose--protein mannosyltransferase
Abolishes E2-inducible strong interaction with ESR1, but not basal interaction.
Abolishes interaction with CBX5 and AURKB.
Decreases interaction with CBX5, abolishes localization to centromeres in interphase; when associated with A-167 and A-169.
Decreases interaction with CBX5, abolishes localization to centromeres in interphase; when associated with A-167 and A-171.
Decreases interaction with CBX5, abolishes localization to centromeres in interphase; when associated with A-169 and A-171.
Loss of binding to CDCA8 and BIRC5; when associated with R-22.
Loss of binding to CDCA8 and BIRC5; when associated with R-34.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with R-35; R-36 and R-39.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with R-35; R-36 and R-40.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with R-35; R-39 and R-40.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with R-36; R-39 and R-40.
Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1
Activating signal cointegrator 1 complex subunit 2
Loss of binding to phosphorylated target proteins, including to phosphorylated RBBP8/CtIP; decrease in DNA repair of double-strand breaks by homologous recombination less efficient than that observed with wild-type protein. Abolishes interaction with IRAK3/IRAK-M. Abolishes IL33-mediated increase of IRAK3/IRAK-M protein levels.
Loss of peptidyl-prolyl cis/trans isomerase activity, nuclear localization and cellular function.
Loss of peptidyl-prolyl cis/trans isomerase activity. No effect on the interaction with IRAK3/IRAK-M. Abolishes IL33-mediated increase of IRAK3/IRAK-M protein levels.
Loss of peptidyl-prolyl cis/trans isomerase activity; decrease in DNA repair of double-strand breaks by homologous recombination slightly less efficient than that observed with wild-type protein. No effect on RBBP8/CtIP.
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Cation channel sperm-associated protein 2
Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 2
LON peptidase N-terminal domain and RING finger protein 1
In PHOAD; unknown pathological significance.
In PHOAR2 and PHOAD; unknown pathological significance.
In PHOAR2; unknown pathological significance.
Solute carrier organic anion transporter family member 2A1
Associated with susceptibility to myocardial infarction type 1; increases activation of MAPK14 by oxidized low density lipoprotein.
Low-density lipoprotein receptor-related protein 8
Microtubule-associated tumor suppressor candidate 2
Ubiquitin-like modifier-activating enzyme 6
Found in a patient with congenital central hypoventilation syndrome; unknown pathological significance.
Found in a small consanguineous family with intellectual disability; unknown pathological significance.
Strongly associated with susceptibility to eating disorders such as anorexia nervosa and bulimia nervosa; associated with poorer episodic memory; may have a protective effect in obsessive-compulsive disorder; impairs localization to secretory granules or synapses; decreases density of dendritic mushroom spines and synapses.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Great loss of sumoylation and 30% reduction in repression activity. Almost complete loss of sumoylation and 70% reduction in repression activity; when associated with R-1192.
In TRPS1; prevents the transport into the nucleus and thus reduces the nuclear TRPS1 concentration consistent with haploinsufficiency.
In TRPS3; in heterozygous status has a milder effect causing TRPS1.
Very little change in sumoylation and 30% reduction in repression activity. Almost complete loss of sumoylation and 70% reduction in repression activity; when associated with R-1201.
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
In AH2; late onset; almost normal activity.
In AH2; late onset; partial loss of activity.
In AH2; nonsalt-wasting form; activity abolished.
In AH2; nonsalt-wasting form; loss of 75% of enzymatic activity for the conversion of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione; no effect on endoplasmic reticulum location.
Lymphokine-activated killer T-cell-originated protein kinase
In SMCD and spondylometaphyseal dysplasia Japanese type.
Helical; Signal-anchor for type III membrane protein
Reduced induction of apoptosis; when associated with F-139; F-153; F-166; F-177 and F-201.
Reduced induction of apoptosis; when associated with F-139; F-153; F-166; F-177 and F-210.
Reduced induction of apoptosis; when associated with F-139; F-153; F-166; F-201 and F-210.
Reduced induction of apoptosis; when associated with F-139; F-153; F-177; F-201 and F-210.
Reduced induction of apoptosis; when associated with F-139; F-166; F-177; F-201 and F-210.
Reduced induction of apoptosis; when associated with F-153; F-166; F-177; F-201 and F-210.
Mildly reduced affinity for HCV protein E2.
Reduced affinity for cholesterol binding.
Reduces binding to integrin; when associated with E-144.
Reduces binding to integrin; when associated with E-148.
Strongly reduced affinity for HCV protein E2.
Strongly reduced affinity for HCV protein E2; when associated with E-196.
Strongly reduced affinity for HCV protein E2; when associated with K-188 or Q-188.
Absence of polyubiquitination. Stability of protein increased. No enhanced apoptosis on ionizing radiation induction. No ubiquitination of AKT1 or MDM2. Decreased p53/TP53 stability. No effect on induction of autophagy during ER stress.
No effect on subcellular localization and inosine transport.
Baculoviral IAP repeat-containing protein 1
Prevents the proper cleavage of pro-CASP9, but does not inhibit the cleavage of pro-CASP3 by CASP9.
Strongly increased catalytic efficiency towards deoxycytidine; when associated with M-104 and A-133.
Strongly increased catalytic efficiency towards deoxycytidine; when associated with V-100 and A-133.
Strongly increased catalytic efficiency towards deoxycytidine; when associated with V-100 and M-104. Strongly increased catalytic efficiency towards deoxythymidine; when associated with L-104.
Strongly increased catalytic efficiency towards deoxythymidine; when associated with A-133.
Chromodomain-helicase-DNA-binding protein 9
Zinc finger SWIM domain-containing protein 5
Cerebral cavernous malformations 2 protein-like
Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial
In COXPD41; unknown pathological significance.
Abolishes interaction with CTBP1 and in part relieves transcription repression; when associated with A-590.
Abolishes interaction with CTBP1 and in part relieves transcription repression; when associated with A-592.
Abolishes interaction with CTBP1. Abolishes interaction with CTBP1; when associated with A-648.
Decreases interaction with CTBP1; when associated with A-645.
Decreases interaction with CTBP1; when associated with A-647.
No effect on interaction with CTBP1. Abolishes interaction with CTBP1; when associated with A-593.
Putative uncharacterized protein MED14OS
Mitogen-activated protein kinase kinase kinase 21
Phosphoserine; by autocatalysis and MAP4K1
Abolishes interaction with ATG8 family proteins, induction of ER fragmentation and ER degradation.
In ALS23; forms cytoplasmic aggregates in patient tissues; no effect on nuclear and cytoplasmic localization; loss of interaction with S100A6.
In ALS23; unknown pathological significance.
In ALS23; unknown pathological significance; changed cytoplasmic localization with decreased association with vesicle-like structures; increased interaction with S100A6.
In ALS23; unknown pathological significance; increased aggregation in the cytoplasm sequestering the wild-type protein in these aggregates; loss of interaction with S100A6.
In ALS23; unknown pathological significance; no effect on aggregation; loss of interaction with S100A6.
Abolishes activation of FASLG/CD95L transcription.
Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-91.
Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-93.
Abolishes phosphorylation by DYRK2. Abolishes phosphorylation by GSK3B at Thr-239.
Abolishes the synergistic activity with SMAD3 to activate TGF-beta-mediated transcription.
Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-89; A-93; and A-286.
Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-286.
Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-93.
Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-93; and A-286.
Complete loss of PAK2-mediated phosphorylation; when associated with A-8; A-89; A-93; and A-286.
Greatly reduced ATF7-mediated transcriptional activity; when associated with A-63. Abolishes interaction with FBXW7; when associated with A-63; A-91 and A-93.
Greatly reduced ATF7-mediated transcriptional activity; when associated with A-73. Abolishes interaction with FBXW7; when associated with A-73; A-91 and A-93.
5,6-dihydroxyindole-2-carboxylic acid oxidase
Associated with blond hair in individuals from the Solomon Islands; rare or absent outside of Oceania.
No effect; when associated with F-362 and S-374.
No effect; when associated with F-362 and V-391.
No effect; when associated with S-374 and V-391.
Conserved oligomeric Golgi complex subunit 7
In VAIHS; there is a decreased expression of the mutant protein compared to wild-type.
Reduces dimerization and enzyme activity.
Abolished interaction with FOXK1 and FOXK2.
Abolishes enzymatic activity. Has no effect on interaction with HCFC1.
Abolishes interaction with HCFC1 without affecting interaction with FOXK1 and FOXK2.
Does not affect interaction with FOXK1 and FOXK2.
Found in a malignant pleural mesothelioma cell line.
Found in a malignant pleural mesothelioma sample.
Found in a malignant pleural mesothelioma sample; somatic mutation.
Found in a malignant pleural mesothelioma sample; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; up-regulates heat shock response; induces formation of amyloid-beta aggregates.
Found in a primary uveal melanoma; somatic mutation; induces cytoplasmic accumulation; loss of deubiquitinase activity; up-regulates heat shock response; induces formation of amyloid-beta aggregates.
In KURIS; loss-of-function variant; increased steady-state level of ubiquitinated H2A are found in patient cells; unable to rescue impaired H2AK119ub deubiquitination when expressed in BAP1-deficient cells; abolishes deubiquitinase activity without affecting its ability to interfere with BRCA1 E3 ligase activity; does not affect localization to the nucleus; has a dominant negative effect on cell growth; does not affect interaction with FOXK1 and FOXK2.
In KURIS; loss-of-function variant; increased steady-state levels of ubiquitinated H2A are found in patient cells; unable to rescue impaired H2AK119ub deubiquitination when expressed in BAP1-deficient cells; does not affect localization to the nucleus.
In KURIS; loss-of-function variant; unable to rescue impaired H2AK119ub deubiquitination when expressed in BAP1-deficient cells; does not affect localization to the nucleus.
In KURIS; unknown pathological significance.
In KURIS; unknown pathological significance; able to rescue impaired H2AK119ub deubiquitination when expressed in BAP1-deficient cells; does not affect localization to the nucleus.
In a lung cancer sample; also found in a malignant pleural mesothelioma cell line; induces cytoplasmic accumulation; loss of deubiquitinase activity; up-regulates heat shock response; induces formation of amyloid-beta aggregates.
In a lung cancer sample; induces cytoplasmic accumulation; impairs deubiquitinase activity; up-regulates heat shock response; induces formation of beta-amyloid aggregates.
Ubiquitin carboxyl-terminal hydrolase BAP1
Abolishes detoxification acivity on methylglyocal-adducted CoA.
Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B.
Abolishes enzymatic activity. Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduces binding to OTUD7B. Removes the glycations and restores histone 3. Reduced localization in lipid rafts; when associated with A-46.
Abolishes oxidation and association with mitochondria. No effect on chaperone activity.
Cysteine sulfinic acid (-SO2H); alternate
Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide.
In PARK7; does not affect protein stability and degradation; does not interfere with homodimerization; decreased detoxification acivity on methylglyocal-adducted CoA.
In PARK7; loss of protection against metal cytotoxicity; decreased detoxification acivity on methylglyocal-adducted CoA.
In PARK7; no apparent effect on protein stability; impaired mitochondrial morphology; no effect on detoxification acivity on methylglyocal-adducted CoA.
In PARK7; strongly decreases enzymatic activity; reduces protein stability and leads to increased degradation; ubiquitinated by PRKN leading to its recognition by HDAC6 and targeting to aggresome where is degraded; interferes with homodimerization; abolishes interaction with PIAS2; reduced localization in lipid rafts; almost abolished detoxification acivity on methylglyocal-adducted CoA.
In PARK7; unknown pathological significance.
Loss of protein and nucleic acid deglycase activity. No effect on mitochondrial translocation. Reduced protease activity. No effect on protection against metal cytotoxicity. No effect on methylglyoxal-adducted glutathione or CoA.
No effect on detoxification acivity on methylglyocal-adducted CoA.
No effect on mitochondrial translocation neither on deglycase activity.
Partially compensates for loss of stability; when associated with P-166.
Probable disease-associated variant found in early-onset Parkinson disease with digenic inheritance; no effect on detoxification acivity on methylglyocal-adducted CoA; the patient also carries PINK1 mutation L-399.
Reduces protein stability. No effect on oxidation.
Reduces protein stability. No effect on oxidation. Reduced localization in lipid rafts; when associated with A-106.
Strongly decreases enzymatic activity. Almost abolishes detoxification acivity on methylglyocal-adducted CoA.
Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide.
Unknown pathological significance; no effect on detoxification acivity on methylglyocal-adducted CoA.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO3)
In CSB; DNA-dependent ATPase-dead mutant; loss of chromatin remodeling activity; loss of its ability to inhibit non-homologous end joining-mediated repair and promote homologous recombination-mediated repair of DNA double-strand breaks; loss of its ability to suppress premature exit from G2/M checkpoint; abrogation of its UV-induced chromatin association.
In POF11; weaker cellular response to DNA damage as indicated by delayed recruitment of mutant protein to DNA damaged sites, compared to ERCC6 isoform 1; no effect on interaction with RNA polymerase II either after UV or H(2)O(2) damage.
Loss of interaction with RIF1; when associated with G-1470 and G-1486.
Loss of interaction with RIF1; when associated with G-1470 and G-1488.
Loss of interaction with RIF1; when associated with G-1486 and G-1488.
Loss of sumoylation and defects in transcription-coupled nucleotide excision repair.
No loss of sumoylation; when associated with R-1457 and R-1487. No loss of sumoylation; when associated with R-1487.
No loss of sumoylation; when associated with R-1457 and R-1489. No loss of sumoylation; when associated with R-1489.
No loss of sumoylation; when associated with R-1487 and R-1489.
Non-phosphorylatable by ATM. Loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain.
Non-phosphorylatable by CDK2. Loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain.
Phosphomimetic mutant. No loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain.
Cytokine-inducible SH2-containing protein
Ral guanine nucleotide dissociation stimulator-like 1
28S ribosomal protein S34, mitochondrial
In COXPD32; significant decrease in protein levels; destabilizes the small ribosomal subunit resulting in impaired mitochondrial translation.
Found in a small consanguineous family with learning disability; unknown pathological significance.
Ubiquitin-like modifier-activating enzyme 7
Malonyl-CoA-acyl carrier protein transacylase, mitochondrial
In PAPA8; decreased transcriptional activity; reduced expression of the GLI1 target PTCH1 observed in patient fibroblasts after chemical induction of the hedgehog pathway.
In PPD1; unknown pathological significance.
Found in a patient with Meckel syndrome; unknown pathological significance.
Found in a patient with autism; unknown pathological significance.
Probable disease-associated variant found in a patient with Joubert syndrome; digenic inheritance; the patient also carries a truncating mutation in CC2D2A.
Probable disease-associated variant found in a patient with Joubert syndrome; digenic inheritance; the patient also carries a truncating mutation in KIF7.
Probable disease-associated variant found in a patient with Joubert syndrome; digenic inheritance; the patient also carries mutation A-1447 in CC2D2A.
Abolishes inhibition of SPRY4-mediated repression of cell spreading. No effect on interaction with SPRY4 or colocalization with SPRY4 at vesicular spots in the cytoplasm.
Dual specificity testis-specific protein kinase 1
In breast cancer samples; infiltrating ductal carcinoma; somatic mutation.
Nuclear receptor subfamily 2 group C member 2
Abolishes activity as transcriptional activator.
Altered sequence specificity, with increased affinity for the DNA sequence 5'-TAATCTAATTA-3'.
Decreased activity as transcriptional activator.
Loss of interaction with EP300 and CREBBP.
No effect on activity as transcriptional activator.
Reduced activity as transcriptional activator.
Cancer/testis antigen family 45 member A1
Intraflagellar transport protein 88 homolog
Serine/threonine-protein phosphatase 4 regulatory subunit 3A
25-fold reduction in binding affinity for RNASE2.
40-fold reduction in binding affinity for RNASE2.
A significant decrease in binding affinity with RNASE1, slight decrease for the ANG ligand, no real change in binding affinity for RNASE2.
Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-264 and A-319.
Substantially decreased binding affinity for RNASE2. Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-262 and A-264.
Substantially decreased binding affinity for RNASE2. Binding affinity decreased 5000-fold over the wild type for RNASE2; when associated with A-262 and A-319.
Substantially decreases binding affinity for RNASE1, ANG and RNASE2.
ATP-binding cassette sub-family G member 8
In STSL1; decreased maturation of glycan chains.
In STSL1; strongly decreased maturation of glycan chains.
In STSL1; unknown pathological significance.
Abolished ability to bind N6-methyladenosine (m6A)-containing RNAs.
Decreased palmitoylation. No degradation of HMGCR.
Impairs the ability of the LBD to induce pore closure. No effect on synapse assembly. No effect on cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not affect motor coordination.
In SCAR18; constitutively open the extracellular-glutamate-gated ion channel.
Monomeric form. Does not dimerize. Weakly interacts with C1q domain of CBLN1. Forms intermediate synapse. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation. Abolishes D-Serine?dependent long term synaptic depression at PF-PC synapses. Does not recover motor coordination in experiment of transfection in Grid2-null mice.
No effect on CBLN1 interaction; when associated with D76.
No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-349. No effect on synapse assembly; when associated with A-343; A-346 and A-349. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-349. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-349. Does not affect motor coordination; when associated with A-343; A-346 and A-349.
No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-346 and A-350. No effect on synapse assembly; when associated with A-343; A-346 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-346 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-346 and A-350. Does not affect motor coordination; when associated with A-343; A-346 and A-350.
No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-343; A-349 and A-350. No effect on synapse assembly; when associated with A-343; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-343; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-343; A-349 and A-350. Does not affect motor coordination; when associated with A-343; A-349 and A-350.
No effect on CBLN1 interaction; when associated with D76. No effect on CBLN1 binding; when associated with D-76; A-346; A-349 and A-350. No effect on synapse assembly; when associated with A-346; A-349 and A-350. No effect on cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-346; A-349 and A-350. Does not affect D-Serine?dependent long term synaptic depression at PF-PC synapses; when associated with A-346; A-349 and A-350. Does not affect motor coordination; when associated with A-346; A-349 and A-350.
Reduces binding to CBLN1; when associated with D76.
Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; A-61 and D-76. Abolishes synapse assembly; when associated with A-24; A-26 and A-61. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-61. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-61.
Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-26; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-26 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-26 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-26 and A-345.
Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-24; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-24; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-24; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-24; A-61 and A-345.
Reduces binding to CBLN1; when associated with D76. Abolishes CBLN1 binding; when associated with A-26; A-61; D-76 and A-345. Abolishes synapse assembly; when associated with A-26; A-61 and A-345. Abolishes cerebellar parallel fiber-Purkinje cell synapse formation; when associated with A-26; A-61 and A-345. Abolishes D-Serine-dependent long term synaptic depression at PF-PC synapses; when associated with A-26; A-61 and A-345.
(E3-independent) E2 ubiquitin-conjugating enzyme
Abolishes cleavage by caspases, inhibits apoptotic membrane blebbing and release of cytochrome c from mitochondria; when associated with A-164.
Abolishes cleavage by caspases, inhibits apoptotic membrane blebbing and release of cytochrome c from mitochondria; when associated with A-238.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-191; E-215; E-228; E-243 and E-246.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-191; E-215; E-228; E-243 and E-282.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-191; E-215; E-228; E-246 and E-282.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-191; E-215; E-243; E-246 and E-282.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-191; E-228; E-243; E-246 and E-282.
Loss of centrosomal localization and reduced ZNF365-binding; when associated with E-215; E-228; E-243; E-246 and E-282.
Nuclear distribution protein nudE homolog 1
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-191; V-215; V-228; V-243 and A-282.
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-191; V-215; V-228; V-243 and V-246.
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-191; V-215; V-228; V-246 and A-282.
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-191; V-215; V-243; V-246 and A-282.
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-191; V-228; V-243; V-246 and A-282.
Retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased ZNF365-binding; when associated with V-215; V-228; V-243; V-246 and A-282.
S-palmitoyl cysteine; by ZDHHC2, ZDHHC3 and ZDHHC7
Germ cell-specific gene 1-like protein 2
In CPVT4; increased RYR2 calcium-release channel activity; not changed calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; not changed thermal stability both in the absence and presence of calcium; no effect on the calcium binding affinity; significantly increased binding of RYR2; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In CPVT4; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) concentrations; increased RYR2 calcium-release channel activity; decreased KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In CPVT6; decreased calcium-binding affinity; not changed binding to RYR2; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed action potential duration.
In LQT14; decreased calcium affinity; loss of CACNA1C calcium-dependent-inactivation; no effect on intracellular RYR2-mediated calcium release.
In LQT14; loss-of-function variant causing impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential; decreased calcium ion binding.
In LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; no effect on RYR2 interaction; significantly reduced ryanodine-sensitive calcium-release channel activity; impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential.
In LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; significantly decreased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In LQT14; significantly decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane; decreased thermal stability in presence of calcium ions; decreased interaction with RYR2.
In LQT15; reduction in calcium affinity.
In LQT15; reduction in calcium affinity; highly decreased calcium-dependent inactivation of L-type calcium channel; increased action potential duration; not changed protein abundance; not changed structure; increased thermal stability in absence of calcium; decreased thermal stability in presence of calcium; significantly increased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In LQT15; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; significantly decreased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In LQT15; the mutant has significantly reduced calcium affinity compared to wild-type; calmodulin-RYR2 interaction is defective at low intracellular Ca(2+) concentrations and restored at moderate to high Ca(2+) concentrations; increased RYR2 calcium-release channel activity; decreased calcium-dependent inactivation of L-type calcium channel; not changed protein abundance; not changed structure; significantly reduced ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
In LQT16; loss-of-function variant causing impaired negative regulation of high voltage-gated calcium channel activity; impaired regulation of cardiac muscle cell action potential; decreased calcium ion binding.
Actin-related protein 2/3 complex subunit 5-like protein
Ubiquitin-conjugating enzyme E2 variant 1
In COFG; unknown pathological significance.
Transcription factor IIIB 90 kDa subunit
In BHC; decrease in DNA-binding; no effect on transcription activation from thyroglobulin/TG, nor from pulmonary surfactant-associated protein C/SFTPC gene promoters.
In BHC; loss of transcription activation.
In BHC; unknown pathological significance.
In NMTC1; loss of transcription regulatory region DNA binding; decreased transcription factor activity, sequence-specific DNA binding; tested for the thyroglobulin gene; associated with dominant impairment of thyroid-specific genes transcription and increased thyroid cells proliferation.
Loss of deubiquitination activity, no change in subcellular location.
In MCPH14; impairs the centriole-forming function of the protein.
Spindle assembly abnormal protein 6 homolog
Abolishes sumoylation; when associated with R-221.
Abolishes sumoylation; when associated with R-536.
Found in a patient with pulmonary arterial hypertension; unknown pathological significance.
Helical; Voltage-sensor; Name=Segment S4
Potassium voltage-gated channel subfamily A member 5
Reduces sumoylation; when associated with N-220.
Reduces sumoylation; when associated with N-535.
In CMD3B; decreased thermodynamic stability; accelerated unfolding, perturbed protein structure; no effect on anchoring function.
In DMD; does not affect protein stability; does not affect protein expression at the sarcolemma; interaction with DAG1 is reduced.
In DMD; results in highly reduced protein levels and expression at the sarcolemma.
In a patient with Becker muscular dystrophy.
In isoform 12, isoform 13, isoform 14, isoform 15, isoform 16 and isoform 17.
In isoform 6, isoform 7, isoform 8, isoform 9 and isoform 10.
In isoform 7, isoform 10 and isoform 16.
In isoform 8, isoform 9, isoform 10, isoform 14, isoform 15 and isoform 16.
In isoform 9, isoform 13 and isoform 15.
In one patient with Becker muscular dystrophy.
Vacuolar protein sorting-associated protein 37D
Ras GTPase-activating-like protein IQGAP3
Abolishes processing, secretion and enzyme activity.
Alteration of the correct processing of heparanase which results in the cleavage at an upstream site in the linker peptide and no activation of proheparanase.
Faster electrophoretic migration typical of a size reduction and important decrease of secretion. Larger size reduction; when associated with Q-162; Q-200; Q-217; Q-238 and Q-459.
Faster electrophoretic migration typical of a size reduction and important decrease of secretion. Larger size reduction; when associated with Q-178; Q-200; Q-217; Q-238 and Q-459.
Faster electrophoretic migration typical of a size reduction and partial decrease in secretion. Larger size reduction; when associated with Q-162; Q-178; Q-200; Q-238 and Q-459.
Faster electrophoretic migration typical of a size reduction and partial decrease in secretion. Larger size reduction; when associated with Q-162; Q-178; Q-217; Q-238 and Q-459.
Faster electrophoretic migration typical of a size reduction. Larger size reduction and important decrease of secretion; when associated with Q-162; Q-178; Q-200; Q-217 and Q-238.
Faster electrophoretic migration typical of a size reduction. Larger size reduction and important decrease of secretion; when associated with Q-162; Q-178; Q-200; Q-217 and Q-459.
Loss of heparanase activity. No effect on HPSE-mediated cell adhesion.
No association with GS-modified heparin; when associated with K-158.
No effect on processing nor secretion. No enzyme activity detected.
No effect on processing, secretion nor enzyme activity.
Two-fold increase in the level of secretion upon addition of GS-modified heparin. No association with GS-modified heparin; when associated with K-161.
Loss of endoribonuclease activity. No effect on RNA-binding.
Loss of endoribonuclease activity. Strongly decreases RNA-binding.
Mildly decreases endoribonuclease activity. No effect on RNA-binding.
In SPG75; alters proper folding; impairs N-glycosylation; retained in the endoplasmic reticulum; increased proteasome-dependent degradation.
In SPG75; unknown pathological significance.
N-linked (GlcNAc...) asparagine; partial
In FANCG; associated with a mild clinical phenotype; disruption of HES1-binding; no effect on FANCA-binding.
Loss of BRCA2-, FANCD2- and XRCC3-binding. No effect on complex formation with FANCA and FANCF.
No effect on BRCA2-, FANCA-, FANCF-, nor XRCC3-binding.
Fat storage-inducing transmembrane protein 1
Cilia- and flagella-associated protein 47
In SPGFX3; unknown pathological significance; loss of protein expression; loss of CFAP65 flagellar location.
In SPGFX3; unknown pathological significance; loss of protein expression; loss of CFAP65 flagellar location; unknown pathological significance.
In SPGFX3; unknown pathological significance; strongly decreased protein expression.
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1
In NPC2; leads to the synthesis of misfolded recombinant proteins that colocalized with an endoplasmic reticulum marker; normally secreted but unable to correct cholesterol storage in NPC2-deficient cells.
In NPC2; results in the synthesis of functional recombinant proteins correctly targeted to lysosomes.
NPC intracellular cholesterol transporter 2
Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2
Almost abolishes interaction with H2AZ1 and H2BC11. Abolishes interaction with H2AZ1 and H2BC11 and exchange of H2A for H2AZ1 in nucleosomes; when associated with A-29--37-A.
Highly decreases interaction with H2AZ1 and H2BC11. Abolishes interaction with H2AZ1 and H2BC11 and exchange of H2A for H2AZ1 in nucleosomes; when associated with A-43--46-A.
Vacuolar protein sorting-associated protein 72 homolog
Caseinolytic peptidase B protein homolog
Decreased ATP hydrolysis activity. Loss of ATP-dependent protein disaggregase activity.
In MGCA7A; decreased ATP hydrolysis activity; decreased ATP-dependent protein disaggregase activity.
In MGCA7B; decreased ATP hydrolysis activity; decreased ATP-dependent protein disaggregase activity; not changed mitochondrial respiration.
In MGCA7B; increased ATP hydrolysis activity; severely decreased ATP-dependent protein disaggregase activity.
In MGCA7B; loss of ATP hydrolysis activity; loss of ATP-dependent protein disaggregase activity.
In MGCA7B; unknown pathological significance.
In MGCA7B; unknown pathological significance; requires 2 nucleotide substitutions.
In SCN9; decreased granulocyte differentiation; decreased ATP hydrolysis activity; decreased ATP-dependent protein disaggregase activity; decreased mitochondrial respiration.
In SCN9; decreased granulocyte differentiation; decreased ATP hydrolysis activity; decreased ATP-dependent protein disaggregase activity; does not render cells more sensitive to ER stress-induced apoptosis.
In SCN9; decreased granulocyte differentiation; loss of ATP hydrolysis activity; loss of ATP-dependent protein disaggregase activity; decreased mitochondrial respiration.
In SCN9; decreased granulocyte differentiation; loss of ATP hydrolysis activity; loss of ATP-dependent protein disaggregase activity; does not render cells more sensitive to ER stress-induced apoptosis.
In SCN9; decreased mitochondrial respiration.
Loss of ATP hydrolysis activity. Loss of ATP-dependent protein disaggregase activity.
No effect on ATP hydrolysis activity. Loss of ATP-dependent protein disaggregase activity.
Normal ATP hydrolysis activity; normal ATP-dependent protein disaggregase activity.
Severely decreased ATP hydrolysis activity. Loss of ATP-dependent protein disaggregase activity.
In NPHS13; abrogates interaction with NUP93.
Abolishes interaction with BCOR and BCORL1.
Abolishes repressor activity. May be a PKC phosphorylation site.
Marked decrease of repressor activity. May be a kinase phosphorylation site.
In isoform RMO1, isoform RMO1a, isoform RMO1b and isoform RMO1ab.
In isoform RMO1c, isoform RMO1ac, isoform RMO1bc and isoform RMO1abc.
Ras-associated and pleckstrin homology domains-containing protein 1
Abolishes membrane subcellular location. Abolishes TEA transport.
Decreases plasma membrane expression. Decreases TEA and metformin transport. Vmax value for TEA transport is decreased.
Decreases plasma membrane expression. Transport of TEA and metformin are reduced by at least 90%.
Does not affect membrane subcellular location. Abolishes TEA transport.
Does not affect membrane subcellular location. Decreases TEA transport.
Does not affect membrane subcellular location. Decreases TEA transport. Higher affinity for cimetidine and reduced affinity to TEA.
Does not affect plasma membrane expression. Decreases TEA and metformin transport. Vmax value for TEA transport is decreased. Km value for TEA is increased.
Does not affect plasma membrane expression. Does not affect TEA and metformin transport.
Does not affect plasma membrane localization. Decreases TEA transport. Km value for TEA is increased. Does not affect metformin transport.
No change in subcellular location and abolition of MATE1-dependent TEA transport activity.
Glutamyl-tRNA(Gln) amidotransferase subunit C, mitochondrial
In COXPD42; decreased protein abundance.
Able to complement a trm8-delta mutant yeast.
Abolished RNA methyltransferase activity.
Abolishes ability to complement a trm8-delta mutant yeast.
Abolishes ubiquitination by the TRIM27:MAGEL2 E3 ubiquitin ligase complex and impairs retrograde transport.
Impairs retrograde transport from endosome to Golgi apparatus.
Compromises nuclear envelope enrichment.
Disrupts LEMD2 accumulation within the nuclear envelope (NE) and subsequent NE core enrichment in anaphase cells.
Does not affect nuclear envelope enrichment.
Failure to enrich at mictrotubule-containing nuclear envelope core during anaphase.
Increases BBS4, BBS8 and BBS9 ciliary localization.
Leucine zipper transcription factor-like protein 1
(Microbial infection) O-acetylserine; by Yersinia YopJ
(Microbial infection) O-acetylserine; by Yersinia YopJ; alternate
(Microbial infection) O-acetylthreonine; by Yersinia YopJ
Phosphoserine; by autocatalysis; alternate
Prevents phosphorylation. Reduces serine and threonine phosphorylation of ARHGEF2.
Receptor-interacting serine/threonine-protein kinase 2
Does not affect oligomer formation; when associated with S-18 and S-23.
Does not affect oligomer formation; when associated with S-18 and S-30.
Does not affect oligomer formation; when associated with S-23 and S-30.
In OSTEOP; associated with disease susceptibility.
Decreased colocalization with PPP1CC by 27%.
O-linked (Xyl...) (glycosaminoglycan) serine
PTB-containing, cubilin and LRP1-interacting protein
Ras association domain-containing protein 4
Epidermal growth factor receptor kinase substrate 8-like protein 3
In HYPT5; unknown pathological significance.
Very weak binding affinity for KANK1 and KANK2.
In a breast infiltrating ductal carcinoma sample; somatic mutation.
In a lung adenocarcinoma sample; somatic mutation.
In an ovarian mucinous carcinoma sample; somatic mutation.
Zinc finger CCCH domain-containing protein 7A
Abolished histidine methylation by METTL9.
Does not affect histidine methylation by METTL9.
Strongly reduced histidine methylation by METTL9.
Metastasis-associated in colon cancer protein 1
Abolishes deubiquitinase activity. No effect on NTRK1 ubiquitination levels.
Ubiquitin carboxyl-terminal hydrolase 36
Associated with increased levels of soluble IL6RB in blood serum.
Does not induce ligand-independent activation.
Found in patient with lung cancer; unknown pathological significance.
In HIES4A; results in impaired cytokine-mediated signaling pathway with loss of response to IL-6, IL-11, OSM and LIF and a weak response to IL-27.
In HIES4A; results in impaired cytokine-mediated signaling pathway with loss of response to IL-6, IL-11, OSM, LIF and a weak response to IL-27.
In HIES4B; results in defective cytokine-mediated signaling pathway with loss of response to IL-6, IL-11, IL-27, OSM but not LIF.
In HIES4B; results in defective cytokine-mediated signaling pathway.
In HIES4B; results in impaired cytokine-mediated signaling pathway with loss of response to IL-6, IL-11, IL-27 and reduced response to OSM, CNTF and LIF.
In IMD94; results in constitutively active IL6-mediated signaling and constitutive phosphorylation of STAT3 in patient cells.
In STWS2; results in impaired cytokine-mediated signaling pathway with loss of response to IL-6, IL-11, IL-27, OSM and LIF; does not localize to the cell membrane.
Results in impaired cytokine-mediated signaling pathway with loss of response to IL-6 and IL-11. Weak response to IL-27, OSM and LIF.
In DM1; unknown pathological significance.
In isoform 2, isoform 3, isoform 4, isoform 5 and isoform 6.
Feline leukemia virus subgroup C receptor-related protein 2
Decreased molecular weight probably due to glycosylation loss, decreased binding to BoNT/A HC.
Decreased molecular weight probably due to glycosylation loss, decreased binding to BoNT/A HC. Greater reduction in weight; when associated with Q-565.
Decreased molecular weight probably due to glycosylation loss, no change in binding to BoNT/A heavy chain. Greater reduction in weight; when associated with Q-559.
No change in interaction with C.botulinum neurotoxin type A heavy chain (botA, BoNT/A HC). Decreased molecular weight probably due to glycosylation loss, decreased interaction with BoNT/A HC.
Abolishes 5' to 3' directional unwinding activity.
Abolishes 5' to 3' directional unwinding activity. Abolishes inhibition of RNA chaperonne activity of LIRE1. No effect on interaction with UPF1.
About 70% more antiviral activity against encephalomyocarditis virus replication; when associated with A-129.
About 70% more antiviral activity against encephalomyocarditis virus replication; when associated with A-869.
Almost complete lost of the ability to prevent the degradation of APOBEC3G mediated by HIV-1 Vif. Attenuated anti-HBV activity.
Guanine nucleotide-binding protein subunit beta-like protein 1
Fumarylacetoacetate hydrolase domain-containing protein 2B
In SSASKS; decreased protein levels; decreased expression at the cell membrane.
In SSASKS; mild skeletal features; results in altered regulation of calcium homeostasis and abnormal distribution of cellular calcium in patient fibroblasts.
In SSASKS; unknown pathological significance.
High mobility group nucleosome-binding domain-containing protein 4
Abolishes deoxyribose-phosphate aldolase activity.
Schiff-base intermediate with acetaldehyde
Changes the plasma lipoprotein distribution of ApoE4 to the HDL.
Found in a patient with hypercholesterolemia; unknown pathological significance; ApoE1 Weisgraber.
Found in a patient with hypercholesterolemia; unknown pathological significance; ApoE4 Freiburg.
In ApoE1 HE; requires 2 nucleotide substitutions.
In ApoE3*; decreased binding to LDL receptor.
In ApoE5; associated with hyperlipoproteinemia and atherosclerosis; increased binding to LDL receptor.
In HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3** are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth; ApoE4 is associated with higher susceptibility to SARS-CoV-2 infection in neurons and astrocytes.
In HLPP3; ApoE1 Harrisburg; decreased binding to LDL receptor; probable dominant negative effect; decreased in vitro binding to heparin.
In HLPP3; ApoE2 Christchurch; decreased binding to LDL receptor.
In HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1 Weisgraber and ApoE3**; ApoE3** is associated with HLPP3; changed protein structure; decreased binding to LDLR and other lipoprotein receptors; decreased in vitro binding to heparin; no effect on distribution among plasma lipoproteins.
In HLPP3; ApoE3 Leiden; no effect on glycosylation.
In HLPP3; ApoE4 Philadelphia, ApoE5 French-Canadian and ApoE5-type; only ApoE4 Philadelphia is associated with HLPP3.
In HLPP3; also found in a patient with hypercholesterolemia; ApoE4 Philadelphia and ApoE2-type.
In HLPP3; unknown pathological significance; ApoE Kochi.
In LPG; ApoE2 Sendai; decreased binding to LDL receptor; induces intraglomerular deposition of ApoE-containing lipoproteins.
In SBHD; also found in patients with a diagnosis of familial combined hyperlipidemia.
Increased binding to LDL receptor; when associated with A-167.
Increased binding to LDL receptor; when associated with R-157.
No effect on plasma lipoprotein distribution.
Restores the LDL receptor binding activity of ApoE2.
Abolishes binding to tRNA. Does not abolish shuttling behavior.
Does not abolish binding to tRNA. Does not abolish shuttling behavior.
Complete loss of activity of the heterotetramer, heterodimer composed of IDH3A and IDH3B subunits and the heterodimer composed of IDH3A and IDH3G subunits with no effect on their oligomeric states.
Complete loss of the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP.
In RP90; unknown pathological significance.
Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial
No significant effect on the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP.
Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate and ADP.
Significantly impairs the activation of the heterodimer composed of IDH3A and IDH3G subunits by citrate.
Cysteine sulfenic acid (-SOH) intermediate; for peroxidase activity
Loss of peroxidase activity, but no effect on phospholipase activity.
Loss of phospholipase activity, but no effect on peroxidase activity.
Abolishes lamellipodia formation and induces filopodia formation.
Found in a patient with a neurodevelopmental disorder; unknown pathological significance; gain-of-function mutation in signal transduction; changed regulation of ERK1 and ERK2 cascade; increased interaction with BRAF; increased interaction with RAF1; loss of phosphorylation by CK1 at Thr-232.
Loss of homodimerization. Reduced dimerization with YWHAE. Significantly reduced interaction with P53. No enhancement of P53 transcriptional activity.
Loss of sphingosine-activated PKA phosphorylation. Promotes homodimerization and heterodimerization with YWHAE. Enhanced transcriptional activity of P53.
On DNA damage, loss of MAPK8-mediated phosphorylation. Loss of binding ABL1. Attenuates ABL1-mediated apoptosis. No loss of interaction with BAX under stress conditions. Inhibits translocation of BAX to mitochondria.
In DEE25; loss of function in citrate transport; loss of localization to plasma membrane.
In DEE25; loss of function in citrate transport; no effect on localization to plasma membrane.
In DEE25; loss of localization to plasma membrane; loss of function in citrate transport.
In DEE25; no loss of localization to plasma membrane; loss of function in citrate transport.
Loss of localization to plasma membrane; loss of function in citrate transport.
No effect on its function in citrate transport.
No effect on localization to plasma membrane; no effect on its function in citrate transport.
No effect on localization to plasma membrane; reduced function in citrate transport; increased Km and Vmax values compared with that of wild type with citrate as substrate.
Significant loss of function in citrate transport.
In IFAP2 and HMD; loss of sterol-regulated protein processing; loss of localization to the nucleus; decreased DNA-binding transcription factor activity RNA polymerase II-specific.
In IFAP2; loss of sterol-regulated protein processing; loss of localization to the nucleus; decreased DNA-binding transcription factor activity RNA polymerase II-specific.
In isoform SREBP-1B and isoform SREBP-1C.
In isoform SREBP-1C and isoform SREBP-1cDelta.
In isoform SREBP-1aDelta and isoform SREBP-1cDelta.
Loss of proteolytic processing in response to low sterol.
Loss of proteolytic processing in response to low sterol. Transcriptionally inactive.
Processed sterol regulatory element-binding protein 1
Sterol regulatory element-binding protein 1
Strong reduction of proteolytic processing in response to low sterol.
Found in a patient with developmental delay with seizures and mild developmental delay; unknown pathological significance.
In RTTCV; the mutant protein extensively, although not fully, localizes in nuclear speckles, while the wild-type is more widely dispersed throughout the nucleus.
Probable disease-associated variant found in a patient with developmental delay.
Found in a patient with congenital cataract and developmental delay; unknown pathological significance.
tRNA-dihydrouridine(20a/20b) synthase [NAD(P)+]-like
Abolishes stable interaction with KLRK1.
Abrogates cell killing and interaction with GRB2. No effect on interaction with PIK3R1.
Abrogates cell killing and interaction with PIK3R1. No effect on interaction with GRB2.
In HAE6; unknown pathological significance.
Interchain (between heavy and light chains)
Low molecular weight growth-promoting factor
Pyrrolidone carboxylic acid; in mature form
Abolishes autophosphorylation and catalytic activity.
Cytochrome c oxidase subunit 5A, mitochondrial
In MC4DN20; decreased protein abundance in patient fibroblasts; decreased proteins abundance of mitochondrial respiratory chain complex IV in patient fibroblasts; no effect on respiratory chain complex IV assembly in patient fibroblasts; increased protein abundance of S1 complex IV intermediate in patient fibroblasts.
Ras-specific guanine nucleotide-releasing factor 1
Cleavage and polyadenylation specificity factor subunit 7
In RP78; decreased function in positive regulation of Rho protein signal transduction; loss of function in regulation of actomyosin structure organization.
In RP78; no effect on function in positive regulation of Rho protein signal transduction; decreased function in regulation of actomyosin structure organization.
Rho guanine nucleotide exchange factor 18
39S ribosomal protein L12, mitochondrial
In COXPD45; MRPL12 steady state level are reduced in patient fibroblasts; results in defective mt-LSU assembly; reduced mitochondrial translation with a significant decrease of synthesis of COXI, COXII and COXIII subunits.
Coiled-coil domain-containing protein 63
Abolishes interaction with APP and gamma-secretase-dependent processing of the APP membrane-anchored C-terminal fragment C83.
Amyloid beta precursor protein binding family B member 2
In isoform Beta, isoform Gamma, isoform Delta and isoform Epsilon.
tRNA-uridine aminocarboxypropyltransferase 1
Ubiquitin carboxyl-terminal hydrolase 24
In CHEDDA; the mutation resulted in a perturbation of the structural and functional integrity of the HX repeat; altered zinc-binding properties of the HX repeat.
In CHEDDA; unknown pathological significance.
Prevents cleavage and suppresses apoptosis.
Loss of autoprocessing. Loss of nuclear membrane localization.
Loss of processing. Loss of nuclear membrane localization.
No effect on autoprocessing. Severe loss of autoprocessing; when associated with A-879.
Found in a patient with multiple sporadic venous malformations; increased ligand-independent autophosphorylation; the autophosphorylation increases when associated with Phe-897.
Found in a patient with multiple sporadic venous malformations; increased ligand-independent autophosphorylation; the hyperphosphorylation increases when associated with Leu-915.
Found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation.
Found in patients with solitary and multiple sporadic venous malformations; increased ligand-independent autophosphorylation; novel location at endoplasmic reticulum and Golgi apparatus; partially retained at endoplasmic reticulum and Golgi apparatus.
In GLC3E; enhanced proteasomal degradation.
In GLC3E; formation of protein aggregates.
In GLC3E; reduced response to ligand; loss of ligand-induced phosphorylation; no effect on basal membrane location.
In GLC3E; unknown pathological significance; 10-fold decrease of Tyr-1102 phosphorylation; no effect on membrane location.
In VMCM; also found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation and kinase activation.
In VMCM; increased ligand-independent autophosphorylation and kinase activation.
In VMCM; increased ligand-independent autophosphorylation and kinase activation; no effect on location at membrane.
In VMCM; strongly increased ligand-independent autophosphorylation and kinase activation.
In an ovarian serous carcinoma sample; somatic mutation.
Variant found in a clone obtained from a fibroblast cell line; does not form the essential disulfide bond; results in loss of antiviral activity.
In allele CYP1A1*2B and allele CYP1A1*2C; displays 5.7- and 12-fold increase in catalytic efficiency in the formation of 2-hydroxylated estrogens, 17beta-estradiol and estrone respectively..
In allele CYP1A1*4; displays similar catalytic efficiency toward estrogens when compared to the wild-type enzyme..
Peptidyl-prolyl cis-trans isomerase A-like 4A
Coiled-coil domain-containing protein 167
In ICRD; functional expression studies in yeast show that the mutant has decreased function under growth conditions requiring the TCA cycle and the glyoxylate shunt.
In CDCBM1; can form tubulin heterodimers that are properly incorporated into microtubules; the microtubules are less stable than wild-type.
In CDCBM1; does not form tubulin heterodimers.
In CDCBM1; does not form tubulin heterodimers; patient fibroblasts show no major alterations in the microtubule network, but the microtubules are less stable than wild-type.
In CDCBM1; reduced heterodimers formation.
In CFEOM3A; affects heterodimers formation; affects microtubules polymerization and depolymerization rates.
In CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules.
In CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures.
In CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures; affects microtubules polymerization and depolymerization rates.
In CFEOM3A; severe phenotype with congenital facial weakness; lower extremity weakness and sensory loss in the second to third decade of life in one patient; affects microtubules polymerization and depolymerization rates.
In CFEOM3A; some patients with lower extremity weakness and sensory loss in the second to third decade of life; also found in patients without CFEOM3A who developed polyneuropathy.
H/ACA ribonucleoprotein complex subunit 1
In a glioblastoma multiforme sample; somatic mutation.
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Loss of ability to hydrolyze sphingosylphosphorylcholine.
Loss of lysophospholipase activity and ability to hydrolyze sphingosylphosphorylcholine.
Reduces lysophospholipase activity by about 50%.
Reduces lysophospholipase activity by about 70%.
Strongly reduced lysophospholipase activity.
In EHMTO; loss of methanethiol oxidation in patient cells.
Epidermal growth factor receptor substrate 15-like 1
Nucleosome-remodeling factor subunit BPTF
Strongly reduces binding to histone H3K4me3.
Found in a patient with obesity; unknown pathological significance.
Melanocortin-2 receptor accessory protein 2
Beta/gamma crystallin domain-containing protein 2
Carcinoembryonic antigen-related cell adhesion molecule 19
Cytoplasmic 60S subunit biogenesis factor ZNF622
Rho guanine nucleotide exchange factor 33
Loss of dsRNA-induced ATPase activity. Loss of ds-RNA binding. No effect on cytoplasmic pattern recognition receptor signaling pathway in response to virus.
Loss of dsRNA-induced ATPase activity. No effect on cytoplasmic pattern recognition receptor signaling pathway in response to virus.
Loss of dsRNA-induced ATPase activity. No effect on ds-RNA binding. No effect on cytoplasmic pattern recognition receptor signaling pathway in response to virus.
Found in a patient with atypical retinitis pigmentosa and a patient with cone dysfunction; unknown pathological significance; no effect on phosphorylation; no effect on subcellular localization.
In RDCP; alters phosphorylation; no effect on subcellular localization; loss of transcriptional coactivator activity.
In RDCP; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity.
In RP27; autosomal dominant; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity.
In RP27; decreases phosphorylation; no effect on subcellular localization; increased transactivational activity; increased transcriptional coactivator activity.
In RP27; decreases phosphorylation; no effect on subcellular localization; increased transcriptional coactivator activity.
In RP27; increased transactivational activity.
In RP27; no effect on phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity.
In RP27; unknown pathological significance; alters phosphorylation; no effect on subcellular localization; no effect on transcriptional coactivator activity.
Neural retina-specific leucine zipper protein
Homologous recombination OB-fold protein
Constitutively active; when associated with D-474.
Constitutively active; when associated with E-309.
Impairs interaction with TTC3; when associated with A-309.
Impairs interaction with TTC3; when associated with A-474.
In HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes.
In NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject.
RAC-beta serine/threonine-protein kinase
In VERBRAS; decreased QRICH1 protein expression; decreased growth plate chondrocyte hypertrophic differentiation; unknown pathological significance.
In VERBRAS; unknown pathological significance.
Testicular spindle-associated protein SHCBP1L
Triggering receptor expressed on myeloid cells 1
Mediates endoplasmic reticulum retention
Thioredoxin domain-containing protein 16
U6 snRNA-associated Sm-like protein LSm4
Abolished interaction with XRCC5 and XRCC6.
Abolished interaction with XRCC5 and XRCC6; impaired localization to the nucleus.
Abolished interaction with XRCC5 and XRCC6; impaired localization to the nucleus; decreased ability to promote non-homologous end-joining (NHEJ).
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-385 and A-421. Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-376 and A-421. Does not affect histone chaperone activity; when associated with A-376 and A-421.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-385 and A-427. Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-376 and A-427. Does not affect histone chaperone activity; when associated with A-376 and A-427.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-379; A-421 and A-427. Does not affect histone chaperone activity; when associated with A-379; A-421 and A-427.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-385; A-421 and A-427. Does not affect histone chaperone activity; when associated with A-385; A-421 and A-427.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-421 and A-427. Does not affect histone chaperone activity; when associated with A-421 and A-427.
Does not affect interaction with XRCC5 and XRCC6.
Does not affect interaction with XRCC5 and XRCC6; decreased ability to promote non-homologous end-joining (NHEJ).
Impaired binding to histones and ability to mediate histone chaperone activity.
Reduced interaction with XRCC5 and XRCC6.
Reduced interaction with XRCC5 and XRCC6; impaired localization to the nucleus.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
Abolishes binding to MHC class II (MHC-II) without affecting interaction with FGL1.
Does not affect binding to MHC class II (MHC-II).
Does not significantly affect binding to MHC class II (MHC-II).
Increased binding to MHC class II (MHC-II).
Reduced binding to MHC class II (MHC-II).
Secreted lymphocyte activation gene 3 protein
Slightly affects binding to MHC class II (MHC-II).
Eukaryotic translation initiation factor 3 subunit H
In DFNA2A; dominant negative effect; abolishes potassium current.
In DFNA2A; loss of potassium selectivity of the pore.
No effect on inhibition by potassium channel toxin SsTX.
Potassium voltage-gated channel subfamily KQT member 4
Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation.
In a patient with focal dermal hypoplasia also carrying a frameshift mutation; uncertain pathological significance.
Protein-serine O-palmitoleoyltransferase porcupine
In CDCBM9; loss-of-function variant resulting in decreased neurite length and impaired neuronal migration in patient-derived nerve cells; no protein detected in patient cells.
In CDCBM9; unknown pathological significance.
No binding with CDC42; no induced pseudopodia formation.
Coiled-coil domain-containing protein 137
Almost completely abolishes AP2B1-binding.
Causes only a slight reduction in AP2B1-binding.
Forkhead-associated domain-containing protein 1
Greatly decreases in vitro transcription inhibition activity.
Abolishes nuclear translocation of ARRB2.
Abolishes nuclear translocation of ARRB2; when associated with A-230 and A-232.
Abolishes nuclear translocation of ARRB2; when associated with A-230 and A-239.
Abolishes nuclear translocation of ARRB2; when associated with A-232 and A-239.
Reduced phosphorylation by PAK1. Reduced microtubule polymerization and loss of phosphorylation by PAK1; when associated with A-128.
Reduced phosphorylation by PAK1. Reduced microtubule polymerization and loss of phosphorylation by PAK1; when associated with A-65.
Cancer/testis antigen family 45 member A5
Cancer/testis antigen family 45 member A6
Cancer/testis antigen family 45 member A7
Abolishes ubiquitin thioesterase activity.
Ubiquitin carboxyl-terminal hydrolase 21
Abolishes catalytic activity; when associated with F-138.
Abolishes catalytic activity; when associated with L-131.
Loss of kinase activity. Increases accumulation of lysosomal cholesterol.
No effect on kinase activity; increased accumulation of lysosomal cholesterol.
Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha
Abolishes interaction with CEP55 and midbody localization; no effect on interaction with ESCRT-I proteins, PDCD6IP and viral proteins.
Loss of interaction with VPS28. No effect on interaction with VPS37C.
No change in interaction with p6; no effect on HIV-1 budding.
Reduces interaction with HIV-1 p6; impairs HIV-1 budding.
Reduces interaction with VPS37B and HIV-1 p6; abolishes interaction with PDCD6IP; impairs HIV-1 budding; inhibits down-regulation of EGFR. Abolishes MGRN1-binding. Loss of interaction with ARRDC1.
Reduces interaction with ubiquitin. No effect on MGRN1-binding.
Reduces interaction with ubiquitin; inhibits down-regulation of EGFR.
Reduces interaction with ubiquitin; no effect on in interaction with HIV-1 p6.
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3
In EPM6; no effect on protein stability; loss of localization to the cis-Golgi network membrane; loss of function; unable to rescue the yeast strain lacking the ortholog Bos1.
IxM motif; signal for cargo packaging into COPII-coated vesicles
Impairs localization at the cell membrane.
Found in a patient with congenital cataract.
Loss of tyrosine phosphatase activity toward H2AX.
Confers phosphatase activity. Dephosphorylates G3BP1 at 'Ser-149'. Loss of interaction with G3BP1. Reduces arsenite-induced stress granule formation.
Serine/threonine/tyrosine-interacting-like protein 1
Almost complete loss of bactericidal activity.
In isoform 3, isoform 4, isoform 6 and isoform 7.
In isoform 4, isoform 5, isoform 7 and isoform 8.
Increases activity 2.3 fold; decrease in plasmin-mediated proteolytic processing; decrease in ability to inhibit nicotine-evoked catecholamine secretion in vitro.
May be associated with a reduced risk for hypertension especially in men; reduces activity 4.7 fold; no effect on plasmin-mediated proteolytic processing; increase in ability to inhibit nicotine-evoked catecholamine secretion in vitro; displays alterations in baroreceptor function.
No effect on plasmin-mediated proteolytic processing; decrease in ability to inhibit nicotine-evoked catecholamine secretion in vitro.
200-fold decrease of sensitivity to CsA. Reduced ability to stimulate MAPK/ERK phosphorylation.
Acetylation-mimetic mutant; no effect on its interaction with TARDBP.
Loss of ability to stimulate MAPK/ERK phosphorylation.
Loss of acetylation and interaction with TARDBP.
Loss of peptidyl-prolyl cis-trans isomerase activity and interaction with HCV NS5A. Loss of ability to stimulate MAPK/ERK phosphorylation.
Loss of peptidyl-prolyl cis-trans isomerase activity.
Loss of peptidyl-prolyl cis-trans isomerase activity. No loss of its interaction with BSG/CD147 or its ability to induce leukocyte chemotaxis. No effect on its interaction with MAP3K5/ASK1. Loss of its ability to negatively regulate oxidative stress-induced apoptosis mediated by MAP3K5/ASK1. Reduced interaction with TARDBP. No loss of interaction with influenza A virus matrix protein 1 or its ability to inhibit viral replication.
N-acetylvaline; partial; in Peptidyl-prolyl cis-trans isomerase A, N-terminally processed
No effect on peptidyl-prolyl cis-trans isomerase activity.
No effect on peptidyl-prolyl cis-trans isomerase activity. Reduced interaction with BSG/CD147 and ability to induce leukocyte chemotaxis.
Peptidyl-prolyl cis-trans isomerase A, N-terminally processed
Reduced ability to stimulate MAPK/ERK phosphorylation.
C-Jun-amino-terminal kinase-interacting protein 3
In NEDBA; affects axon development when expressed in a heterologous system.
In NEDBA; unknown pathological significance.
In COXPD14; results in a 4-fold decrease in the catalytic efficiency of amino acid activation mainly due to a decreased affinity for ATP; does not affect Phe binding; affects the stability of the enzyme, leading to a significant decrease in overall charging capacity.
In COXPD14; results in a decrease in affinity for Phe causing a decrease in aminoacylation activity; affects the stability of the enzyme, leading to a significant decrease in overall charging capacity.
In COXPD14; results in decreased affinity for tRNA causing a decrease in the catalytic efficiency for tRNA charging; does not affect ATP or Phe binding.
In SPG77; resulted in severely impaired phenylalanine-tRNA ligase activity.
Phenylalanine--tRNA ligase, mitochondrial
Abolishes interaction with ARRDC3; when associated with A-795 and A-868.
Abolishes interaction with ARRDC3; when associated with A-795 and A-920.
Abolishes interaction with ARRDC3; when associated with A-868 and A-920.
Guanine nucleotide exchange protein SMCR8
Impaired autophagosome maturation; when associated with A-402.
Impaired autophagosome maturation; when associated with A-796.
Loss of C9ORF72-SMCR8 complex-mediated stimulation of RAB8A and RAB11A GTPase activity.
Phosphomimetic mutant; able to promote autophagosome maturation; when associated with D-402.
Phosphomimetic mutant; able to promote autophagosome maturation; when associated with D-796.
In IMD99; when expressed in a B lymphocyte cell line, leads to decreased frequencies of somatic hypermutations, a process involved in the production of isotype-switched high-affinity antibodies, the defect that can be rescued by the wild-type protein; decrease interaction with AICDA, hence impairs AICDA nuclear localization; may decrease protein stability; no effect on interaction with CDC5L.
Abolishes cleavage by caspase-3 and subsequent induction of apoptosis.
Nuclear factor of activated T-cells, cytoplasmic 2
Asymmetric dimethylarginine; by CARM1; alternate
Asymmetric dimethylarginine; by PRMT6; alternate
In GLM; non-brain stem pediatric glioblastoma and diffuse intrinsic pontine glioma; somatic mutation; results in a global decrease of H3K27me3 levels.
Phosphoserine; alternate; by AURKB, AURKC and RPS6KA5
Phosphoserine; alternate; by AURKB, AURKC, RPS6KA3, RPS6KA4 and RPS6KA5
Probable disease-associated variant found in pediatric undifferentiated soft tissue sarcoma samples; somatic mutation; also found in a subset of human papillomavirus-negative head and neck squamous cell carcinomas; results in global decrease of H3K36me2 and H3K36me3 levels and increased H3K27me3 levels.
Probable disease-associated variant found in pediatric undifferentiated soft tissue sarcoma samples; somatic mutation; results in global decrease of H3K36me2 and H3K36me3 levels and increased H3K27me3 levels.
Symmetric dimethylarginine; by PRMT5; alternate
Coiled-coil domain-containing protein 66
Loss of association with microtubules and localization to centrosomes.
Ventricular zone-expressed PH domain-containing protein homolog 1
PGC-1 and ERR-induced regulator in muscle protein 1
Does not abolish protein nuclear export. Abolishes almost completely acetylation.
Greatly reduced acetylation and 85% reduction in transcriptional activity. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-409.
Greatly reduced interaction with DNA and JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-44 and A-43.
Increased transcriptional activity. Further increased transcriptional activity; when associated with S-208.
Increased transcriptional activity. No further increase in transcriptional activity with EP300.
Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-40; A-41 and A-44.
Little effect on interaction with DNA or JUN. Abolishes interaction with DNA and JUN; when associated with A-41; A-43 and A-44.
Little effect on interaction with DNA or JUN. Abolishes interaction with JUN; when associated with A-40; A-41 and A-43.
Mothers against decapentaplegic homolog 3
No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-341 and R-378.
No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-333; R-378 and R-409.
No effect on acetylation. Completely abolishes acetylation and 97% reduction in transcriptional activity; when associated with R-341; R-378 and R-409.
Phosphothreonine; by CDK2, CDK4 and MAPK
Reduced interaction with JUN. Loss of transcriptional activity and cooperation with JUN.
Reduced phosphorylation, increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-179 and A-213.
Reduced phosphorylation, increased transcriptional and increased antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and A-213.
Reduced phosphorylation. Increased transcriptional and antiproliferative activities. Further increase in transcriptional and antiproliferative activities; when associated with V-8 and V-179.
In MRD57; exhibits abnormal perinuclear localization instead of diffuse nuclear localization; impairs kinase activity; reduced phosphorylation of ASF1A.
In MRD57; reduced phosphorylation of ASF1A.
In MRD57; severely reduced kinase activity.
In MRD57; unknown pathological significance.
In MRD57; unknown pathological significance; exhibits abnormal perinuclear localization instead of diffuse nuclear localization; mildly impairs kinase activity; reduced phosphorylation of ASF1A.
Loss of kinase activity. No impact on interaction with ASF1A.
Serine/threonine-protein kinase tousled-like 2
BTB/POZ domain-containing protein KCTD19
Ankyrin repeat domain-containing protein SOWAHD
In a patient with gray platelet syndrome.
Abolishes phosphoinositide binding and localization to the Golgi apparatus; when associated with A-171 or L-171.
Abolishes phosphoinositide binding and localization to the Golgi apparatus; when associated with A-174.
Abolishes phosphoinositide binding and localization to the Golgi apparatus; when associated with A-81.
Abolishes phosphoinositide binding and localization to the Golgi apparatus; when associated with A-90.
Loss of function in vesicle budding, abolishes phosphoinositide binding and localization to the Golgi apparatus.
DNA-directed RNA polymerase II subunit RPB4
O-linked (Xyl...) (heparan sulfate) serine
Loss of IRS1 ubiquitination and degradation.
Myosin light chain kinase 2, skeletal/cardiac muscle
Potassium voltage-gated channel subfamily H member 8
Calcium/calmodulin-dependent protein kinase type IV
Fully active Ca2+/CaM-independent kinase; when associated with 309-A--A-312. Loss of interaction with PPP2CA/PPP2CB.
Fully active Ca2+/CaM-independent kinase; when associated with 320-A-A-321.
In a lung large cell carcinoma sample; somatic mutation.
Increases phosphorylation of CREB1 2-fold. Decreases total O-linked glycosylation 2-fold. Increases ATP-binding affinity.
Loss of activity; dominant negative form.
Protein mono-ADP-ribosyltransferase PARP8
Catalytic mutant. Abolishes ability to methylate mt-tRNA(Met).
In C2A; catalytic mutant. Abolishes ability to methylate mt-tRNA(Met).
In COXPD48; unknown pathological significance.
tRNA (cytosine(34)-C(5))-methyltransferase, mitochondrial
Found in a patient with Klippel-Feil syndrome; unknown pathological significance.
In isoform 3, isoform 4, isoform 5, isoform 6, isoform 7 and isoform 10.
Potassium voltage-gated channel subfamily S member 2
Jupiter microtubule associated homolog 1
Jupiter microtubule associated homolog 1, N-terminally processed
N-acetylthreonine; in Hematological and neurological expressed 1 protein, N-terminally processed
Leads to reduced autophagosome formation under autophagy-inducing conditions.
Leads to the accumulation of autophagosomes under normal growth conditions.
Loss of decapping activity; when associated with Q-148.
RanBP2-like and GRIP domain-containing protein 3
Abrogates binding to CHEK2; when associated with A-96 and A-97.
Abrogates binding to CHEK2; when associated with A-96 and A-98.
Abrogates binding to CHEK2; when associated with A-97 and A-98.
Abrogates binding to the MRE11 complex and to CHEK2.
Mediator of DNA damage checkpoint protein 1
Suppresses RNF4-mediated ubiquitination, accumulates at sites of DNA damage, defective homologous recombination.
Complete loss of TBK1 and RB1CC1 binding.
CREB-regulated transcription coactivator 2
Impaired phosphorylation under low glucose conditions and impaired interaction with 14-3-3 proteins; when associated with A-171.
Loss of cAMP- and calcium-regulated phosphorylation. Greatly reduced interaction with 14-3-3 proteins. Impaired phosphorylation under low glucose conditions and impaired interaction with 14-3-3 proteins; when associated with A-274.
No effect on cAMP- and calcium-regulated phosphorylation.
Phosphoserine; by AMPK, MARK2, SIK1 and SIK2
Reduced cAMP- and calcium-regulated phosphorylation.
Leucine-rich repeat-containing protein 66
Peptidyl-prolyl cis-trans isomerase FKBP9
In MCC2D; has some wild-type residual activity.
In MCC2D; produces severely decreased wild-type residual activity.
In MCC2D; shows virtually no enzyme activity.
In MCC2D; unknown pathological significance.
Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial
Reduced binding to phosphatidylinositol 3,4-bisphosphate.
Reduced binding to phosphatidylinositol 4,5-bisphosphate.
In AOVD3; loss of endothelial barrier function in a dextran permeability assay.
In AOVD3; unknown pathological significance.
In AOVD3; unknown pathological significance; requires 2 nucleotide substitutions.
Zinc finger B-box domain-containing protein 1
Elongation of very long chain fatty acids protein 7
Loss of activity alone or when associated with A-151.
Loss of activity; when associated with A-150.
Branched-chain-amino-acid aminotransferase, cytosolic
In EVR2 and ND; reduced amount of protein in the extracellular matrix.
In EVR2; the patient presented significant phenotypic heterogeneity between the two eyes.
In ND; reduction of protein amount in the extracellular matrix.
In ND; unknown pathological significance.
In persistent fetal vasculature syndrome.
Abolishes homodimerization of the TPR domain. Slightly reduced enzyme activity; when associated with D-211.
Abolishes homodimerization of the TPR domain. Slightly reduced enzyme activity; when associated with E-208.
In XLID106; decreased protein abundance; decreased enzyme activity; reduced protein stability.
In XLID106; decreased protein abundance; reduced protein stability.
In XLID106; unknown pathological significance.
Loss of enzyme activity. Moderate increase in KMT2E ubiquitination. Moderate increase in KMT2E ubiquitination; when associated with A-508.
Reduces enzyme activity by about 95%. Moderate increase in KMT2E ubiquitination; when associated with A-508.
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit
Completely abolishes interaction with KLC1.
Ankyrin repeat domain-containing protein SOWAHC
Dominant negative effect on the ERK1/ERK2 signaling pathway and EPO-induced erythroid differentiation.
Malignant fibrous histiocytoma-amplified sequence 1
In IDDAS; de novo variant; does not affect nuclear localization; no effect on transcriptional repression of FEZF2; does not affect homodimerization; does not affect interaction with FOXP2; does not affect interaction with BCL11A.
In IDDAS; de novo variant; localizes to the nucleus but forms abnormal aggregates; no effect on transcriptional repression of FEZF2; does not affect homodimerization; abolishes interaction with FOXP2; does not affect interaction with BCL11A.
In IDDAS; de novo variant; localizes to the nucleus but forms abnormal aggregates; no effect on transcriptional repression of FEZF2; does not affect homodimerization; severely decreased interaction with FOXP2; loss of interaction with FOXP1; does not affect interaction with BCL11A.
In IDDAS; unknown pathological significance; does not affect nuclear localization; no effect on transcriptional repression of FEZF2; does not affect homodimerization; decreased interaction with FOXP2; loss of interaction with BCL11A.
In IDDAS; unknown pathological significance; does not affect nuclear localization; no effect on transcriptional repression of FEZF2; does not affect homodimerization; does not affect interaction with FOXP2.
In IDDAS; unknown pathological significance; does not affect nuclear localization; no effect on transcriptional repression of FEZF2; does not affect homodimerization; does not affect interaction with FOXP2; does not affect interaction with BCL11A.
Impairs UBE2S-mediated polyubiquitination, decreasing substrate affinity. Does not affect UBE2C-mediated multiubiquitination.
Reduced infection with Yellow fever virus, Zika virus and Dengue virus; no effect on mobilization of neutral lipids from lipid droplets.
Reduced infection with flaviviruses such as Yellow fever virus, Zika virus and Dengue virus; no effect on mobilization of neutral lipids from lipid droplets.
In LNCR; unknown pathological significance.
Decreases expression of IFNB1 mRNA following infection with Sendai virus.
Tubulin--tyrosine ligase-like protein 12
Secretory carrier-associated membrane protein 1
In EPM7; causes a dominant-negative loss of current upon membrane depolarization.
Potassium voltage-gated channel subfamily C member 1
Doublesex- and mab-3-related transcription factor C1
A disintegrin and metalloproteinase with thrombospondin motifs 14
Found in a patient with a complex hereditary motor and sensory neuropathy form associated with dysarthria, joints hypermobility and cerebellar signs; unknown pathological significance.
Nearly abolishes export from the nucleus.
FERM, ARHGEF and pleckstrin domain-containing protein 1
Abolishes interaction with ITSN1 and location at clathrin-coated pits; when associated with S-576.
Abolishes interaction with ITSN1 and location at clathrin-coated pits; when associated with S-607.
Impaired recruitment to the cell membrane.
Increased recruitment to the cell membrane.
Loss of ability to promote actin polymerization; when associated with A-478.
Loss of ability to promote actin polymerization; when associated with A-480.
Loss of ability to promote actin polymerization; when associated with A-521.
Loss of ability to promote actin polymerization; when associated with A-524.
Does not affect ability to activate transcription in vitro.
Impaired ability to activate transcription in vitro.
Impaired, but not abolished, ability to activate transcription in vitro.
In CMD1; 17% of wild-type DNA binding activity; shows a 2-fold reduction in nuclear import efficiency; transcriptional activation is only reduced to 62% of wild-type activity.
In CMD1; 5% of wild-type DNA binding activity; transcriptional activation is only reduced to 26% of wild-type activity.
In CMD1; decreased 75% transactivational activity.
In CMD1; dimerization and the resulting capacity to activate promoters via dimeric binding sites is lost; other features of the protein function remain unaltered.
In CMD1; mild form overlapping with small patella syndrome; decreased 50% transactivational activity.
In CMD1; residual DNA binding and transactivation of regulated genes.
Phytanoyl-CoA dioxygenase domain-containing protein 1
Calcium/calmodulin-dependent protein kinase type II subunit gamma
In MRD59; gain-of-function variant affecting regulation of neurite formation and arborization; results in constitutive autophosphorylation.
In isoform 2, isoform 8, isoform 9 and isoform 11.
In isoform 6, isoform 7, isoform 8 and isoform 9.
Mitochondrial import inner membrane translocase subunit TIM44
Abolishes iron-binding and promotes its degradation.
Nuclear pore complex-interacting protein family member A1
In GSS deficiency; 10-fold decreased glutathione synthase activity.
In GSS deficiency; 100-fold decreased glutathione synthase activity.
Disrupts spindle localization and interaction with TACC3.
Disrupts spindle localization; when associated with E-444, E-445, E-500 and E-506.
Disrupts spindle localization; when associated with E-444, E-445, E-500 and E-507.
Disrupts spindle localization; when associated with E-444, E-445, E-506 and E-507.
Disrupts spindle localization; when associated with E-444, E-500, E-506 and E-507.
Disrupts spindle localization; when associated with E-445, E-500 E-506 and E-507.
Disrupts spindle localization; when associated with E-481, E-487, E-500 and E-506.
Disrupts spindle localization; when associated with E-481, E-487, E-500 and E-507.
Disrupts spindle localization; when associated with E-481, E-487, E-506 and E-507.
Disrupts spindle localization; when associated with E-481, E-500, E-506 and E-507.
Disrupts spindle localization; when associated with E-487, E-500, E-506 and E-507.
In MRD56; unknown pathological significance.
In DFNB74; abolishes zinc-binding and enzymatic activity.
Reduces inhibition of CLOCK-BMAL1 heterodimer activity; when associated with E-36.
Reduces inhibition of CLOCK-BMAL1 heterodimer activity; when associated with R-45.
Tumor necrosis factor receptor superfamily member 4
Glucosamine 6-phosphate N-acetyltransferase
Reduces affinity for glucosamine-6-phosphate 6-fold.
No stimulation of granule polarization during NK-mediated cytotoxicity, abolishes activation of CD244/2B4-mediated cytotoxicity, abolishes augmentation of CD244/2B4-triggered PLCG1 phosphorylation and ERK activation.
Gamma-aminobutyric acid receptor-associated protein
Impairs localization at the autophagosomal membrane.
No effect on WDFY3-binding. Impaired WDFY3-binding, but no effect on SQSTM1-binding; when associated with H-25 and H-54.
No effect on WDFY3-binding. Impaired WDFY3-binding, but no effect on SQSTM1-binding; when associated with Q-24 and H-25.
No effect on WDFY3-binding. Impaired WDFY3-binding, but no effect on SQSTM1-binding; when associated with Q-24 and H-54.
Found in a patient with epidermolysis bullosa simplex with unspecified subtype; unknown pathological significance.
In DDD1; unknown pathological significance.
In EBS2A; unknown pathological significance.
In EBS2A; unknown pathological significance; dbSNP:.
In EBS2B and EBS2A; unknown pathological significance.
In EBS2B; unknown pathological significance.
In EBS2C and EBS2B; unknown pathological significance.
In EBS2C and in a patient with epidermolysis bullosa simplex with unspecified subtype; unknown pathological significance; requires 2 nucleotide substitutions.
In EBS2C; unknown pathological significance.
In EBS2D; unknown pathological significance.
Increase in keratin-positive aggregates and keratin intermediate filament networks that are very thin and sparse with short filaments.
No effect on interaction with KRT14 or keratin intermediate filament networks.
Probable disease-associated variant found in a patient with EBS with an unspecified subtype.
Spermatogenesis-associated serine-rich protein 1
Nuclear pore complex-interacting protein family member B13
Heterogeneous nuclear ribonucleoprotein H3
Cilia- and flagella-associated protein 45
In HTX11; loss of panaxonemal expression in respiratory cilia and in sperm flagella.
Probable methyltransferase-like protein 25
Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5
In SPG8; does not alter subcellular distribution; no effect on its binding to VCP; no effect on assembly in the WASH complex.
In SPG8; dopamine responsive spasticity.
In SPG8; fails to rescue the curly phenotype in a zebrafish model; no effect on assembly in the WASH complex.
Pulmonary surfactant-associated protein D
In ECTD15; loss of cystein protease inhibitory activity toward cathepsin L, cathepsin V and legumain.
Abolishes protein and lipid kinase activity. Does not abolishes interaction with GRK2.
In IMD97; loss of phosphatidylinositol-3,4-bisphosphate 5-kinase activity.
In IMD97; loss-of-function variant unable to rescue reduced T-cell activation when expressed in Jurkat PIK3CG-deficient cells.
Loss of autophosphorylation. No effect on phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
Loss of kinase activity. Loss of autophosphorylation. Reduced inflammatory reactions but no alterations in cardiac contractility.
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
Decreased methyltransferase activity of the heterodimer complex formed with METTL3.
Does not affect interaction with METTL3.
Does not affect methyltransferase activity of the heterodimer complex formed with METTL3.
Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-192.
Little or no effect on methyltransferase activity of the heterodimer complex formed with METTL3.
Little or no effect on methyltransferase activity. Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-173.
N6-adenosine-methyltransferase non-catalytic subunit
Reduced RNA-binding. Reduced RNA-binding; when associated with E-255.
Reduced RNA-binding; when associated with E-245.
Strongly decreased methyltransferase activity of the heterodimer complex formed with METTL3, probably due to reduced RNA-binding.
Strongly reduced methyltransferase activity of the heterodimer complex formed with METTL3.
Protein-lysine N-methyltransferase EEF2KMT
Abolishes AMPK-mediated phosphorylation.
Found in a patient with non-insulin-dependent diabetes mellitus; does not affect activity.
In NIDDM; reduced transactivation activity.
In isoform HNF4-Alpha-2 and isoform HNF4-Alpha-8.
In isoform HNF4-Alpha-3 and isoform HNF4-Alpha-9.
In isoform HNF4-Alpha-7, isoform HNF4-Alpha-8 and isoform HNF4-Alpha-9.
Phosphomimetic mutant that leads to reduced ability to bind DNA.
Chymotrypsin-like elastase family member 3B
Almost abolishes expression. Abolishes membrane localization.
Expression levels reduced by 40%. No significant change in ligand binding capacity or affinity. Reduced G protein-mediated cAMP signaling but no effect on G protein-mediated calcium release.
Expression levels reduced by 50%. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G-protein mediated calcium release.
Slightly reduced expression levels. No significant change in ligand binding capacity or affinity. No significant change in G protein-mediated cAMP or calcium release.
Slightly reduced expression levels. Remains localized in membrane. Abolishes ligand binding and G protein-mediated calcium release.
Slightly reduced expression levels. Significantly reduced ligand binding capacity but increased affinity. Reduced G protein-mediated cAMP release but no effect on G protein-mediated calcium release.
In a colorectal adenocarcinoma sample; somatic mutation.
Abolishes cleavage by proprotein convertases.
Abolishes interaction with E2 ubiquitin ligases.
CCR4-NOT transcription complex subunit 4
Strongly reduced interaction with UBE2D2.
Strongly reduces interaction with E2 ubiquitin ligases.
Found in infertile men; unknown pathological significance.
Found in infertile men; unknown pathological significance; decreased induction of target genes expression.
Found in a patient with age-related macular degeneration; unknown pathological significance.
Guanine nucleotide-binding protein subunit alpha-15
Advanced glycosylation end product-specific receptor
Zinc finger and BTB domain-containing protein 24
In CMTRIC; in vitro assay suggests a defect in activating the NF-kappa-B signaling pathway.
In DSMA4; stability and intracellular location affected severely impairing the NF-kappa-B transduction pathway.
Pleckstrin homology domain-containing family G member 5
Aflatoxin B1 aldehyde reductase member 2
In COD5; results in protein misfolding and retention in the endoplasmic reticulum.
In IMD84; no effect on homodimerization activity; no effect on heterodimerization activity; changed localization; changed DNA-binding transcription activator activity; changed sequence-specific DNA binding; binds novel and non-specific DNA motifs and acts as a dominant negative through its homodimerization and heterodimerization activities.
T-cell-specific surface glycoprotein CD28
Iroquois-class homeodomain protein IRX-2
Abolishes CK2 phosphorylation. Strongly decreases repressor activity on E-cadherin/CDH1 and CLDN1 promoters. Increases protein stability. Affects function in cell survival. Abolishes phosphorylation in the serine-rich region; when associated with A-104 and A-107.
Abolishes LATS2 phosphorylation. Does not affect binding to LATS2. Reduces protein stability. Equally distributed between nucleus and cytoplasm. Increases capacity to associate with nuclear pore importins. Unable to accumulate in the nucleus. Does not abrogate function.
Abolishes PKA phosphorylation. Strongly decreases repressor activity on E-cadherin/CDH1 and CLDN1 promoters. Increases protein stability. Affects function in EMT.
Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization.
Abolishes recognition and ubiquitination by BTRC which increases steady state level and half-life. Preferentially localizes to the nucleus. Induces a more aggressive tissue invasion program. Lower sensitivity to BTRC-triggered degradation, impairs phosphorylation by GSK3B and does not affect NOTCH1-induced degradation; when associated with A-100. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-100; A-107; A-111; A-115 and A-119.
Abolishes repressor activity on E-cadherin/CDH1 promoter and binding to KDM1A.
Decreases repression activity on E-cadherin/CDH1, occludin and aromatase promoters. Preferentially localizes to the cytoplasm. Abolishes phosphorylation by PAK1.
Does not affect E-cadherin repression; when associated with R-9.
Does not affect E-cadherin/CDH1 repression; when associated with R-16.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-191. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-161 and/or E-220.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-161.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-170. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-187 and/or E-220.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-220 and E-222. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-220.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-220 and E-224.
Does not affect binding to KPNB1, KPNA2, IPO7 or TNPO1. No change in subcellular localization. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1; when associated with E-222 and E-224. Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1 and abolishes nuclear localization, DNA binding and repressor activity on E-cadherin/CDH1 promoter; when associated with E-224. Abolishes binding to KPNB1, KPNA2, IPO7 and TNPO1 and nuclear localization; when associated with E-161 and/or E-187.
Does not affect binding to KPNB1, KPNA2, IPO7, TNPO1 or DNA.
Does not affect repressor activity on E-cadherin/CDH1 promoter.
Exclusively localizes to the cytoplasm. Reduces capacity to associate with nuclear pore importins. Unable to enter the nucleus. Does not abrogate function.
Impairs binding to KPNB1 and IPO7 and abolishes binding to KPNA2 and TNPO1 and nuclear localization.
Impairs binding to KPNB1, IPO7 and TNPO1 and abolishes binding to KPNA2. Localizes to cytoplasm and nucleus.
Impairs binding to KPNB1, KPNA2, IPO7 and TNPO1. No change in subcellular localization.
Increases protein stability, does not affect repressor activity on E-cadherin/CDH1 promoter, preferentially localizes to the nucleus, induces a more aggressive tissue invasion program and impairs phosphorylation by GSK3B, binding to BTRC and ubiquitination; when associated with A-107. Impairs phosphorylation in the serine-rich domain/region; when associated with A-92 and A-107. Abolishes phosphorylation at S-96.
Loss of binding to KPNB1 and nuclear import; when associated with E-191 and A-193.
Lower sensitivity to BTRC-triggered degradation and impaired phosphorylation by GSK3B; when associated with A-96. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-107; A-111; A-115 and A-119. Does not affect NOTCH1-induced degradation; when associated with A-96. Abolishes phosphorylation at S-96.
Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-111 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-111 and A-115.
Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-111 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-111 and A-119.
Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-107; A-115 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-107; A-115 and A-119.
Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-111; A-115 and A-119. Lower sensitivity to BTRC-triggered degradation, impaired phosphorylation by GSK3B and loss of cytoplasmic localization; when associated with A-96; A-100; A-111; A-115 and A-119. Increases protein stability, does not affect repressor activity on E-cadherin promoter, preferentially localizes to the nucleus, induces a more aggressive tissue invasion program and impairs phosphorylation by GSK3B, binding to BTRC and ubiquitination; when associated with A-104. Impairs phosphorylation in the serine-rich region; when associated with A-92 and A-104. Abolishes phosphorylation at S-96.
Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated with R-137. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation; when associated with R-98 and R-137.
Lower sensitivity to FBXL14-triggered degradation. Lower sensitivity to FBXL14-triggered degradation; when associated with R-146. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation and loss of ability to repress E-cadherin; when associated with R-98 and R-146.
Mildly reduces binding to KPNB1 and nuclear import.
Mildly reduces binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with A-193. Loss of binding to KPNB1 and nuclear import; when associated with A-193 and A-196.
Mildly reduces binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with A-228.
Mildly reduces binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with E-191. Loss of binding to KPNB1 and nuclear import; when associated with E-191 and A-196.
Mildly reduces binding to KPNB1. Does not affect binding to KPNA2, IPO7 or TNPO1.
No change. Complete loss of sensitivity to FBXL14- and BTRC-triggered degradation and loss of ability to repress E-cadherin/CDH1; when associated with R-137 and R-146.
Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-115.
Predominantly localized to the cytoplasm; when associated with E-107; E-111 and E-119.
Predominantly localized to the cytoplasm; when associated with E-107; E-115 and E-119.
Predominantly localized to the cytoplasm; when associated with E-111; E-115 and E-119.
Very minor effect on binding to KPNB1 and nuclear import. Strongly reduces binding to KPNB1 and nuclear import; when associated with E-224.
Phosphofurin acidic cluster sorting protein 1
Epithelial splicing regulatory protein 2
ATP synthase subunit e, mitochondrial, N-terminally processed
Bromodomain adjacent to zinc finger domain protein 2A
In OCMD; unknown pathological significance.
In RP88; unknown pathological significance.
Heterogeneous nuclear ribonucleoprotein A0
Abolishes interaction with TYROBP, and strongly reduces activation properties.
No effect on interaction with TYROBP, but strongly reduces activation properties.
In CMT2DD; no effect on Na(+)-dependent currents.
In CMT2DD; shows fewer Na(+)-dependent currents than wild-type protein.
In CMT2DD; unknown pathological significance.
In CMT2DD; unknown pathological significance; requires 2 nucleotide substitutions.
In HOMGSMR2; results in altered sodium and potassium transport as shown by in vitro functional expression of the homologous rat variant.
Sodium/potassium-transporting ATPase subunit alpha-1
Uridine diphosphate glucose pyrophosphatase NUDT14
Polypeptide N-acetylgalactosaminyltransferase 17
In RP61; the mutant protein is retained in the endoplasmic reticulum.
Found in a patient with intellectual disability, short stature, chronic lung disease and failure to thrive; unknown pathological significance.
Abolishes most of in vitro phosphatase activity.
No effect on in vitro phosphatase activity.
Found in individuals with Bombay phenotype.
Found in individuals with para-Bombay phenotype.
Found in individuals with para-Bombay phenotype; allele H3.
Found in individuals with para-Bombay phenotype; allele H4.
Found in individuals with para-Bombay phenotype; allele H5.
Galactoside alpha-(1,2)-fucosyltransferase 1
Almost no sphinganine-1-phosphate aldolase activity.
In NPHS14; probable disease-associated variant also found in a patient with isolated primary adrenal insufficiency; decreased protein abundance; increased aggregation; decreased sphinganine-1-phosphate aldolase activity.
In NPHS14; unknown pathological significance.
In NPHS1; decreased protein abundance in cells of patients homozygous for the mutation; increased aggregation; decreased sphinganine-1-phosphate aldolase activity.
Loss of sphinganine-1-phosphate aldolase activity.
N6-(pyridoxal phosphate)lysine; alternate
No effect on the sphinganine-1-phosphate aldolase activity; no effect on protein abundance.
Probable disease-associated variant found in patients with atypical form of axonal peripheral neuropathy, characterized by acute or subacute onset and episodes of recurrent mononeuropathy.
In VRNI; largely mislocalized to the cytoplasm whereas the wild-type protein is localized near the cell surface.
Rho guanine nucleotide exchange factor 6
Abolished cleavage by S.pyogenes effector protein SpeB, preventing pyroptosis.
Spontaneous pyroptosis-inducing activity.
Coiled-coil domain-containing protein 73
Abolished conjugation of one SUMO1P1/SUMO5. Loss of 2 sumoylations; when associated with R-65 with or without R-133. No effect on nuclear body formation; when associated with R-65. No sumoylation nor nuclear body formation; when associated with R-65 and R-160. Loss the ability to be conjugated by SUMO1P1/SUMO5 but could be conjugated by SUMO1; when associated with R-65 and R-160.
Abolishes ubiquitination by the BCR(KLHL20) E3 ubiquitin ligase complex.
Compromised the formation of high molecular weight species of SUMO1P1/SUMO5 conjugation on PML. Loss of 2 sumoylations; when associated with or without R-65. No sumoylation nor nuclear body formation; when associated with or without R-65 and R-490. Loss the ability to be conjugated by SUMO1P1/SUMO5 but could be conjugated by SUMO1; when associated with R-65 and R-490.
Does not affect SUMO1P1/SUMO5 conjugation.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in /SUMO5); alternate
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1P1/SUMO5); alternate
In isoform PML-11, isoform PML-12 and isoform PML-13.
Loss of 2 sumoylations; when associated with R-65 and R-490.
Loss of 2 sumoylations; when associated with R-65 with or without R-133. No effect on nuclear body formation; when associated with R-65. No sumoylation nor nuclear body formation; when associated with R-65 and R-160.
Loss of 2 sumoylations; when associated with or without R-65. No sumoylation nor nuclear body formation; when associated with or without R-65 and R-490.
Loss of cleavage by enterovirus 71 protease 3C.
Loss of nuclear localization. Reduced acetylation. Further decrease in acetylation; when associated with R-515.
Loss of nuclear localization; when associated with A-487.
Loss of nuclear localization; when associated with A-490.
Loss of one sumoylation. No effect on nuclear body formation. Loss of 2 sumoylations; when associated with R-490 with or without R-133 or R-150. No effect on nuclear body formation; when associated with R-490. Loss the ability to be conjugated by SUMO1P1/SUMO5 but could be conjugated by SUMO1; when associated with R-160 and R-490.
Loss of one sumoylation. No effect on nuclear body formation. Loss of 2 sumoylations; when associated with R-490 with or without R-133 or R-150. No effect on nuclear body formation; when associated with R-490. No sumoylation nor nuclear body formation; when associated with R-160 and R-490.
No nuclear microspeckle location, no sumoylation and loss of intrinsic transcriptional repressor activity of PML-RARA oncoprotein; when associated with R-89.
No nuclear microspeckle location, no sumoylation and loss of intrinsic transcriptional repressor activity of PML-RARA oncoprotein; when associated with S-88.
Slightly reduced acetylation. Further decrease in acetylation; when associated with R-487.
Strongly reduced sumoylation; when associated with S-57.
Strongly reduced sumoylation; when associated with S-60.
2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial
In a lung squamous cell carcinoma sample; somatic mutation.
In a metastatic melanoma sample; somatic mutation.
In LICAS; no UBR7 protein detected in patient cells.
In LICAS; unknown pathological significance.
Putative E3 ubiquitin-protein ligase UBR7
Found in a patiend with developmental delay, cleft palate and proliferative retinopathy; unknown pathological significance.
In ETM5; dominant negative effect on central nervous myelination and axon guidance; changed localization to the plasma membrane; clustered plasma membrane localization.
In ETM5; unknown pathological significance.
Complete loss of ubiquitination activity on MAP3K7/TAK1.
Complete loss of ubiquitination activity on TICAM1.
In FSGSNEDS; also found in a patient with Coffin-Siris syndrome carrying a likely pathogenic ARID2 mutation.
In FSGSNEDS; disrupts localization to nuclear bodies.
N-alpha-acetyltransferase 38, NatC auxiliary subunit
Interferon-related developmental regulator 1
Decreases phenacetin O-deethylation activity 10 fold.
Decreases phenacetin O-deethylation activity 2 fold.
Decreases phenacetin O-deethylation activity 20 fold.
Decreases phenacetin O-deethylation activity 3 fold.
Decreases phenacetin O-deethylation activity 40 fold.
Decreases phenacetin O-deethylation activity 7 fold.
Decreases phenacetin O-deethylation activity 8 fold.
Decreases phenacetin O-deethylation activity 9 fold.
In allele CYP2A13*3 and allele CYP2A13*8.
Increases phenacetin O-deethylation activity 3 fold.
Increases phenacetin O-deethylation activity 5 fold.
Reduces Acyl-CoA thioesterase activity and peroxisome proliferation.
Abolishes palmitoylation, leading to impaired homooligomeization and decreased catalytic activity; when associated with 328-A-A-329.
Abolishes palmitoylation, leading to impaired homooligomeization and decreased catalytic activity; when associated with A-343.
Does not affect localization to the endoplasmic reticulum.
Impaired localization to the endoplasmic reticulum.
In CILD11; unknown pathological significance.
Interleukin-1 receptor type 2, membrane form
Interleukin-1 receptor type 2, soluble form
Abolished nicotinamide-nucleotide adenylyltransferase activity; abolished ability to promote mono-ADP-ribosylation of ribosomes.
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2
Impaired internalization to the trans-Golgi network; when associated with A-861.
Impaired internalization to the trans-Golgi network; when associated with A-864.
Leucine-rich repeat-containing G-protein coupled receptor 5
Does not affect nucleoside-triphosphatase activity. Does not affeet KM for GDP.
Ectonucleoside triphosphate diphosphohydrolase 6
Decreased transport reaction kinetics; decreased affinity for zinc ions; decreased zinc ion import into organelle; no effect on protein abundance.
Decreased zinc ion transmembrane transport.
Decreased zinc ion transmembrane transport; when associated with A-106.
Decreased zinc ion transmembrane transport; when associated with A-137.
Decreased zinc ion transmembrane transport; when associated with A-220.
Decreased zinc ion transmembrane transport; when associated with A-345.
HCH Motif; seals regulatory zinc-binding pocket
Loss of transported zinc binding and decreased zinc ion transmembrane transport; when associated with N-110.
Loss of transported zinc binding and decreased zinc ion transmembrane transport; when associated with N-224.
Strongly reduced affinity for peptide substrate.
Does not affect Ca(2+) affinity as measured by isothermal titration calorimetry of the mutant protein.
Abolishes dimerization. Reduced affinity for E.coli Dr adhesins.
Carcinoembryonic antigen-related cell adhesion molecule 5
No effect on dimerization. Reduced affinity for E.coli Dr adhesins.
Intermembrane lipid transfer protein VPS13C
Mediator of RNA polymerase II transcription subunit 11
In SPGF18; unknown pathological significance.
Probable inactive tRNA-specific adenosine deaminase-like protein 3
Abolishes binding to sumoylated proteins and ubiquitination and degradation of XPC; when associated with 300-A--A-303 and 326-A--A-329.
Abolishes binding to sumoylated proteins and ubiquitination and degradation of XPC; when associated with 300-A--A-303 and 382-A--A-385.
Abolishes binding to sumoylated proteins and ubiquitination and degradation of XPC; when associated with 326-A--A-329 and 382-A--A-385.
No loss of affinity toward SUMO1 and SUMO2.
Zinc finger C3H1 domain-containing protein
Telomere repeats-binding bouquet formation protein 2
Delta-1-pyrroline-5-carboxylate synthase
In ADCL3; no effect on protein abundance; altered sub-mitochondrial distribution; decreased proline biosynthetic process.
In ARCL3A; does not affect proline and ornithine biosynthetic activity.
In SPG9A; altered homohexamerization; no effect on localization to the mitochondrion; loss of glutamate 5-kinase activity; no effect on glutamate-5-semialdehyde dehydrogenase activity; decreased amino acid biosynthetic process.
In SPG9A; decreased protein abundance; no effect on localization to the mitochondrion; altered homohexamerization; loss of glutamate 5-kinase activity; no effect on glutamate-5-semialdehyde dehydrogenase activity; decreased amino acid biosynthetic process.
Loss of enzymatic activity, no loss of B3GNT2-binding and activation.
UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8
In allele NAT1*11; catalyzes the N-acetylation of aromatic amines and the O- and N,O-acetylation of their N-hydroxylated metabolites at rates up to 2-fold higher.
In allele NAT1*17; a slow acetylator; has defective enzyme activity.
No effect on NEDD4-binding. No effect on the disruption of the interaction between INSR and IRS1 and IRS2.
No effect on NEDD4-binding; when associated with A-136 and A-139.
No effect on NEDD4-binding; when associated with A-136 and A-141.
No effect on NEDD4-binding; when associated with A-139 and A-141.
No net loss of phosphorylation, this may be due to a compensatory phosphorylation of T-422 in vitro.
Phosphoserine; by MAPK1 and MAPK3; in vitro
Partial loss of homodimerization; when associated with A-154.
Partial loss of homodimerization; when associated with A-182.
Pleckstrin homology domain-containing family H member 1
In APMR4; changed localization; the protein is present in the ER but is also mislocalized to the cytoplasm.
In APMR4; unknown pathological significance.
In CTRCT44; associated with hypotrichosis; unknown pathological significance.
In CTRCT44; loss of lanosterol synthase activity.
In HYPT14; changed localization; the protein is present in the ER but is also mislocalized to the cytoplasm.
In HYPT14; the protein is present in the ER but also mislocalized to the cytoplasm.
Chloride intracellular channel protein 6
Helical; Note=After insertion into the membrane
cAMP-dependent protein kinase type II-alpha regulatory subunit
Decreases hexamer stability and catalytic efficiency.
In isoform 1, isoform 2, isoform 4, isoform 6 and isoform 7.
In isoform 1, isoform 4, isoform 5, isoform 6 and isoform 7.
Nuclear transcription factor Y subunit gamma
Junctional cadherin 5-associated protein
Found in a patient with childhood focal epilepsy; unknown pathological significance.
Found in a patient with infantile-onset epilepsy; unknown pathological significance.
Found in a patient with intellectual disability and language delay; unknown pathological significance.
Found in a patient with sinus bradychardia; unknown pathological significance; affects channel properties as it results in a negative shift in the threshold voltage of activation and slower activation kinetics compared to the wild-type.
In DEE24; absence of hyperpolarization-activated currents; highly reduced amount of protein at the cell membrane.
In DEE24; affects channel gating properties; the half-activation voltage is shifted to the depolarizing direction; significantly faster activation and slower deactivation kinetics than wild-type channel.
In DEE24; dominant-negative mutation resulting in gain of channel function.
In DEE24; dominant-negative mutation resulting in loss of channel currents.
In DEE24; results in a gain of channel function.
In DEE24; results in absence of hyperpolarization-activated currents; reduced amount of protein at the cell membrane.
In DEE24; the half-activation voltage is shifted to the depolarizing direction; reduced amount of protein at the cell membrane.
In DEE24; unknown pathological significance.
In GEFSP10; affects channel gating properties as the half-activation voltage is shifted to the depolarizing direction; reduced amount of protein at the cell membrane.
In GEFSP10; affects channel gating properties as the half-activation voltage is shifted to the hyperpolarizing direction.
In GEFSP10; decreased current densities; half-activation voltage is slightly shifted to the hyperpolarizing direction.
In GEFSP10; decreased current density; voltage-dependence of activation as well as the activation and deactivation kinetics are not altered.
In GEFSP10; results in a depolarizing shift of the half-activation voltage and faster activation kinetics.
In GEFSP10; significantly decreased current densities.
In GEFSP10; unknown pathological significance.
In GEFSP10; unknown pathological significance; reduced current density; affects channel gating properties as the half-activation voltage is shifted to the depolarizing direction; neurons expressing mutant channels show increased excitability.
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Probable ATP-dependent RNA helicase DHX40
In DIJOS; unknown pathological significance.
Found in a patient with chronic pancreatitis; unknown pathological significance.
Found in a patient with chronic pancreatitis; unknown pathological significance; catalytic activity comparable to that of wild type.
Found in a patient with chronic pancreatitis; unknown pathological significance; catalytic activity comparable to that of wild type; the mutant undergoes proteolytic degradation during trypsin-mediated activation.
Found in a patient with chronic pancreatitis; unknown pathological significance; mutant protein secretion, activity and trypsin-mediated degradation are comparable to those of wild-type.
Found in a patient with chronic pancreatitis; unknown pathological significance; the mutant is not secreted.
Found in patients with chronic pancreatitis; unknown pathological significance.
In PCTT; associated with disease susceptibility; highly reduced catalytic efficiency.
In PCTT; associated with disease susceptibility; impaired catalytic activity.
In PCTT; associated with disease susceptibility; results in altered enzyme specificity and loss of activity.
In PCTT; associated with disease susceptibility; results in reduced protein secretion and loss of activity.
In PCTT; associated with susceptibility to disease; reduced protein secretion; impaired catalytic activity.
In PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion and loss of activity.
In PCTT; associated with susceptibility to disease; results in markedly reduced protein secretion.
In PCTT; associated with susceptibility to disease; results in reduced secretion; normal activity; the mutant undergoes proteolytic degradation during trypsin-mediated activation.
In PCTT; associated with susceptibility to disease; slightly reduced activity.
In PCTT; associated with susceptibility to disease; the mutant is not secreted.
Rare variant that may be associated with susceptibility to pancreatitis; results in markedly reduced protein secretion.
Rare variant; found in a patient with chronic pancreatitis; unknown pathological significance.
Rare variant; results in impaired protein secretion.
Rare variant; results in normal secretion and activity.
Patatin-like phospholipase domain-containing protein 2
Reduces rate of lipid hydrolysis; does not affect the localization around the rim of the adiposomes.
Does not affect phosphorylation by PLK1.
Strongly impairs phosphorylation by PLK1.
Has no effect on N-methyltransferase activity.
Loss of N-methyltransferase activity like its citrullinated counterpart.
In GM2G1; infantile; inactive or unstable protein.
In GM2G1; infantile; loss of processing to a mature form; increased degradation.
In GM2G1; juvenile; fails to associate with the beta-subunit to form the enzymatically active heterodimer.
In GM2G1; late onset; inhibited subunit dissociation; loss of processing to a mature form; increased degradation.
In GM2G1; mild; associated with spinal muscular atrophy.
In GM2G1; unknown pathological significance.
No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-115 and Q-157.
No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-115 and Q-295.
No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-157 and Q-295.
Ubiquitin carboxyl-terminal hydrolase 40
Potassium-transporting ATPase subunit beta
N-linked (GlcNAc...) (high mannose) asparagine
Pancreatic secretory granule membrane major glycoprotein GP2
Abolished phosphorylation by PCK1, does not affect oxysterol-binding, does not affect the interaction with SCAP.
Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR.
Phosphomimetic mutant, reduced binding to oxysterol.
Low-density lipoprotein receptor-related protein 1B
Abolishes AMPK-mediated phosphorylation; when associated with A-722.
Abolishes AMPK-mediated phosphorylation; when associated with A-792.
Stress-associated endoplasmic reticulum protein 1
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
Loss of 5hmc binding; when associated with A-195; A-197; A-199 and A-201.
Loss of 5hmc binding; when associated with A-195; A-197; A-199 and A-203.
Loss of 5hmc binding; when associated with A-195; A-197; A-201 and A-203.
Loss of 5hmc binding; when associated with A-195; A-199; A-201 and A-203.
Loss of 5hmc binding; when associated with A-197; A-199; A-201 and A-203.
50% Decrease in microtubule-binding after in vitro phosphorylation of mutant protein.
70% decrease in microtubule-binding after in vitro phosphorylation of mutant protein.
8% decrease in microtubule-binding after in vitro phosphorylation of mutant protein.
Deamidated asparagine; in tau and PHF-tau; partial
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); in PHF-tau
In FTD and CBD; reduction in the ability to promote microtubule assembly.
In FTD/Alzheimer disease; accelerates aggregation of tau into filaments; reduces tau phosphorylation in cells compared to both the wild-type and other mutant forms.
In FTD; increased aggregation propensity and altered binding affinity towards microtubules and F-actin.
In FTD; less able to promote microtubule assembly than wild-type tau.
In FTD; minimal parkinsonism; very early age of onset.
In FTD; most common mutation; reduction in the ability to promote microtubule assembly; accelerates aggregation of tau into filaments.
In FTD; reduced the ability of tau to promote microtubule assembly without having a significant effect on tau filament formation; effects at both the RNA and the protein level.
In FTD; reduces the ability of tau to promote microtubule assembly and promotes fibril formation in vitro.
In FTD; ultrastructural and biochemical characteristics indistinguishable from Alzheimer disease; accelerates aggregation of tau into filaments.
In PIDB; 90% reduction in the rate of microtubule assembly.
In PIDB; in vitro the mutation reduces the ability of tau to promote microtubule assembly by 25 to 30%.
In PIDB; markedly reduced ability of tau to promote microtubule assembly.
In PIDB; reduces the ability to promote microtubule assembly by 70%.
In PSNP1/atypical PSNP1; heterozygosity may be a risk factor for both a PSNP1-like syndrome and Parkinson disease; reduced the ability of tau to promote microtubule assembly without having a significant effect on tau filament formation; effects at both the RNA and the protein level.
In PSNP1; delays assembly initiation and lowers the mass of microtubules formed; but the assembly rate is increased compared to normal tau.
In fatal respiratory hypoventilation; unusual apparent autosomal recessive inheritance; reduced binding to microtubules as well as increased fibrillization and aggregation.
In isoform Tau-A, isoform Tau-B, isoform Tau-C and isoform Fetal-tau.
In isoform Tau-A, isoform Tau-B, isoform Tau-C, isoform Tau-D, isoform Tau-E, isoform Tau-F and isoform Fetal-tau.
In isoform Tau-A, isoform Tau-B, isoform Tau-D, isoform Tau-E and isoform Fetal-tau.
In isoform Tau-A, isoform Tau-D and isoform Fetal-tau.
N-linked (Glc) (glycation) lysine; in PHF-tau; in vitro
No decrease in microtubule-binding and nucleation activity after in vitro phosphorylation of mutant protein.
Phosphoserine; by MARK1, MARK2, MARK3, MARK4, BRSK1, BRSK2 and PHK
Phosphothreonine; by BRSK1, BRSK2, DYRK2 and PDPK1
Phosphothreonine; by GSK3-beta and PDPK1
Guanine nucleotide-binding protein G(t) subunit alpha-2
Developmental pluripotency-associated 5 protein
Endoplasmic reticulum membrane sensor NFE2L1
In m4; Slightly impaired protein cleavage.
In m6; Slightly impaired protein cleavage.
In DLACD; probable enzymatic loss-of-function; contrary to the wild-type protein, unable to restore basal D-lactate levels when tested in knockout zebrafish model.
Probable D-lactate dehydrogenase, mitochondrial
In allele HCR*WWCC; associated with psoriasis.
Sperm acrosome membrane-associated protein 4
Associated with neonatal thrombocytopenia; alloantigen Duv(a+); does not affect significantly the integrin function.
In BDPLT24; the mutant protein is constitutively active; decreased platelet surface expression; spontaneous FAK phosphosphorylation; abnormal cell shape.
In BDPLT24; the mutant protein is constitutively active; spontaneous FAK phosphosphorylation; abnormal cell shape.
In GT2; gain-of-function mutation; constitutively binds ligand-induced binding sites antibodies and the fibrinogen-mimetic antibody PAC-1.
In GT2; may confer constitutive activity to the alpha-IIb/(mutated)beta-3 receptor.
In GT2; not expressed on the surface and absent inside the transfected cells.
In GT2; severe type 1 phenotype; the mutation prevented normal ITGA2B/ITGB3 complex expression on the cell surface.
In GT2; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation interupts the interaction of the ITGA2B/ITGB3 complex.
In GT2; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression on the cell surface; the mutation may interfere with correct folding of the protein.
In GT2; severe type 1 phenotype; the mutation prevents normal ITGA2B/ITGB3 complex expression.
In alloantigen MO(+); in a case of neonatal alloimmune thrombocytopenia.
Phosphothreonine; by PDPK1 and PKB/AKT1; in vitro
DNA-directed RNA polymerase II subunit RPB11-b1
In NEDCHS; alters the assembly of the Integrator complex.
In NEDCHS; occurs in a splice site resulting in altered splicing and probable nonsense-mediated mRNA decay.
Cysteine sulfonic acid (-SO3H); alternate
Androgen-dependent TFPI-regulating protein
In DEE58; unknown pathological significance.
In OBHD; expressed normally on the cell surface; results in markedly impaired ligand-induced phosphorylation as well as impaired downstream MAPK1 phosphorylation.
In OBHD; unknown pathological significance.
In a lung carcinoma sample; somatic mutation.
In isoform TrkB-T1 and isoform TrkB-N-T1.
Kinase inactive. Fails to activate NF-kappa-B.
Mitogen-activated protein kinase kinase kinase 13
Hydroxyacylglutathione hydrolase-like protein
Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
Displays impaired G1/S transition and S/G2 progression.
Found in patient with severe intellectual disability; unknown pathological significance.
In HH6; phenotype consistent with Kallmann syndrome.
In HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism.
In HH6; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; some patients also carry mutations in FGFR1.
Abolishes interaction with the iron-sulfur transfer complex composed of HSC20, HSPA9 and ISCU and reduces binding to SDHB.
In MC2DN2; abolishes binding to the iron-sulfur transfer complex formed by HSC20, HSPA9 and ICSU; prevents interaction with SDHB; leads to rapid degradation of SDHAF1.
In MC2DN2; rapid degradation of SDHB by the LONP1 protease; increased levels of HIF1A and EPAS1/HIF2A which correlates with succinate accumulation.
In MC2DN2; reduces but does not prevent interaction with HSC20 or SDHB.
LYR motif 1; required for interaction with HSC20
LYR motif 2; not required for interaction with HSC20
Retains reduced ability to interact with HSC20 and SDHB.
Succinate dehydrogenase assembly factor 1, mitochondrial
In MNGMA; found in a case of childhood clear cell meningioma; associated with disease susceptibility.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
Increases sensitivity to several nonselective or family selective PDE inhibitors.
Reduces interaction with RAF1; when associated with A-454 and A-455.
Reduces interaction with RAF1; when associated with A-460 and A-461.
Phosphatidylethanolamine-binding protein 4
Impairs the charge selectivity for paracellular ion transport, favoring Cl(-) transport.
No effect on charge selectivity for paracellular ion transport.
Reverses the charge selectivity for paracellular ion transport, favoring Cl(-) transport.
Decreased enzyme specific activity. Increased PAPC/POPC activity ratio.
Found in a patient with intermediate phenotype between LCATD and FED; reduction of activity.
In FED; results in reduced protein secretion and activity.
In LCATD; also found in a patient with intermediate phenotype between LCATD and FED; loss of activity.
In a patient with low HDL-cholesterol levels; reduced protein secretion.
In a patient with low HDL-cholesterol levels; results in reduced activity.
In a patient with low HDL-cholesterol levels; the mutant is hardly secreted and is catalytically inactive.
Increased activity towards PAPC. Increased PAPC/POPC activity ratio.
Little change in enzyme specific activity nor in PAPC/POPC activity ratio.
Phosphatidylcholine-sterol acyltransferase
In ECTD12; unknown pathological significance.
Aldehyde dehydrogenase family 3 member B1
In WARBM1; abolishes GEF activity towards RAB18; loss of RAB18 membrane association; no effect on GAP activity; no effect on GAP activity towards the RAB3 proteins RAB5A or RAB43.
Rab3 GTPase-activating protein catalytic subunit
Common variant that contributes to hyperglycinuria and iminoglycinuria in patients carrying variants in SLC36A2, SLC6A19 or SLC6A18; results in SLC6A20 inactivation due to a 8-fold decrease of Vmax.
Sodium- and chloride-dependent transporter XTRP3
Impaired ATP-binding. Strong interaction with HIF1A, MET, KEAP1 and RHOBTB2. Loss of interaction with HSF1 and ERBB2. Los of interaction with TSC1.
Loss of interaction with TOMM70. No effect on interaction with IRF3.
Loss of interaction with TSC1 and increases interacrion with AHSA1.
No deffect on the interaction with TSC1.
Reduces ATPase activity and client protein activation.
Strong ATP-binding. Strong interaction with HSF1, HIF1A, ERBB2, MET, KEAP1 and RHOBTB2. No effect on interaction with TSC1.
Leucine-rich repeat flightless-interacting protein 1
Loss of binding to negatively charged membranes, diffuse cytosolic distribution.
28S ribosomal protein S18b, mitochondrial
Odontogenic ameloblast-associated protein
Found in a patient with dysmorphic facies, syndactyly, congenital microcephaly and global developmental delay; unknown pathological significance.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
Impairs dsRNA binding but not dimerization or activity.
In DYT33; gain-of-function variant resulting in increased levels of phosphorylated EIF2AK2 and EIF2A in patient cells compared to controls.
In DYT33; unknown pathological significance.
In DYT33; unknown pathological significance; gain-of-function variant resulting in increased levels of phosphorylated EIF2AK2 and EIF2A in patient cells compared to controls.
In FL-PKR-2AI; moderate loss of activity but no effect on dsRNA binding.
In LEUDEN; unknown pathological significance.
In LEUDEN; unknown pathological significance; reduced phosphorylation of eukaryotic translation initiation factor 2-alpha in patient cells.
Interferon-induced, double-stranded RNA-activated protein kinase
Moderate loss of activity; when associated with A-242 and A-255.
Moderate loss of activity; when associated with A-255 and A-258.
No effect on enzymatic activity; when associated with A-83; A-88 and A-89.
No effect on enzymatic activity; when associated with A-83; A-88 and A-90.
No effect on enzymatic activity; when associated with A-83; A-89 and A-90.
No effect on enzymatic activity; when associated with A-88; A-89 and A-90.
Significant loss of activity and impairs autophosphorylation of T-451.
Significant loss of activity; loss of dsRNA binding and dimerization.
Aspartate beta-hydroxylase domain-containing protein 2
Found in a patient with connective tissue disorder and peripheral neuropathy; unknown pathological significance; decreased secretion; accumulates in the endoplasmic reticulum.
Decreased binding to single-stranded DNA; when associated with E-240; 252-E--E-256; A-279; E-304; E-310 and A-327.
Decreased binding to single-stranded DNA; when associated with E-240; E-248; 252-E--E-256; A-279; E-304 and A-327.
Decreased binding to single-stranded DNA; when associated with E-240; E-248; 252-E--E-256; A-279; E-304 and E-310.
Decreased binding to single-stranded DNA; when associated with E-240; E-248; 252-E--E-256; A-279; E-310 and A-327.
Decreased binding to single-stranded DNA; when associated with E-240; E-248; 252-E--E-256; E-304; E-310 and A-327.
Decreased binding to single-stranded DNA; when associated with E-240; E-248; A-279; E-304; E-310 and A-327.
Decreased binding to single-stranded DNA; when associated with E-248; 252-E--E-256; A-279; E-304; E-310 and A-327.
In DSKOD; increases cAMP production upon activation of ADRB1.
Sperm protein associated with the nucleus on the X chromosome C
Loss of localization to endoplasmic reticulum membrane.
Motile sperm domain-containing protein 2
Prevents binding to the FFAT motif of target proteins STARD3, STARD3NL, RMDN3, OSBPL1A and CERT1 and impairs recruitment to interorganelle membrane contacts; when associated with D-404.
Prevents binding to the FFAT motif of target proteins STARD3, STARD3NL, RMDN3, OSBPL1A and CERT1 and impairs recruitment to interorganelle membrane contacts; when associated with D-406.
In DFNB108; impairs plasma membrane location; abolishes downstream NFkB activation.
Inactive tyrosine-protein kinase transmembrane receptor ROR1
ADP-ribosylation factor GTPase-activating protein 2
Ankyrin repeat and death domain-containing protein 1B
T-cell activation inhibitor, mitochondrial
Coiled-coil domain-containing protein 71
Abolishes lipid kinase activity. Does not affect ability to associate with the TIM22 complex and mediate import of transmembrane proteins into the mitochondrial inner membrane.
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2
Constitutively active mutant that cannot be phosphorylated and further activated by AMPK.
High affinity immunoglobulin alpha and immunoglobulin mu Fc receptor
Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32
Neuroblastoma suppressor of tumorigenicity 1
Enhances osteogenic differentiation in C2C12 cells.
In MPS1H and MPS1H/S; in 3% of the MPS1H patients; reduces catalytic activity and protein stability.
In MPS1H/S; reduction of activity and protein levels.
In MPS1H; loss of function; undetectable enzyme activity.
In MPS1S and MPS1H/S; associated with L-188 in a patient with MPS1H/S; significant reduction of activity and protein levels.
In GIDID2; decreased interaction with TTC7A resulting in reduced PI4K complex stability; no effect on kinase activity.
In NEDSPLB; loss of kinase activity; no effect on protein abundance.
In NEDSPLB; unknown pathological significance.
In SPG84; unknown pathological significance.
In MC4DN5; unknown pathological significance.
Leucine-rich PPR motif-containing protein, mitochondrial
In HAE7; unknown pathological significance.
Abolishes in vitro STAT4 binding to a phosphorylated Y-800 peptide.
Loss of STAT4 activation. Abolishes SOCS3 binding.
No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide.
No loss of STAT4 activation. No loss of SOCS3 binding.
Chondroitin sulfate glucuronyltransferase
Abolishes GRID2 interaction.; when associated with A-122 and A-124.
Abolishes GRID2 interaction.; when associated with A-122 and A-147.
Abolishes GRID2 interaction.; when associated with A-124 and A-147.
Abolishes hexamer formation; when associated with S-34. Abolishes interaction with NRXN1 isoform 3B; when associated with S-34. Abolishes GRID2 interaction.; when associated with S-34.
Abolishes hexamer formation; when associated with S-38. Abolishes interaction with NRXN1; when associated with S-38. Abolishes GRID2 interaction; when associated with S-38.
Reduced ferroxidase activity; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease.
Retained in the ER due to impaired N-glycosylation; may present a vulnerability factor for iron induced oxidative stress in Parkinson disease.
Tumor necrosis factor ligand superfamily member 4
In an ovarian clear cell carcinoma sample; somatic mutation.
Serine/threonine-protein kinase 3 20kDa subunit
Serine/threonine-protein kinase 3 36kDa subunit
Abolishes interaction with LDLRAP1 and ARRB1. Greatly reduces DENND1B-binding.
Strongly reduces interaction with ARRB1.
Strongly reduces interaction with EPN1. Reduces interaction with SNAP91 and clathrin. No effect on EPS15 binding.
Strongly reduces interaction with LDLRAP1 and ARRB1. No effect on DENND1B-binding.
Strongly reduces interaction with LDLRAP1, ARRB1 and EPN1. No effect on DENND1B-binding.
Strongly reduces interaction with LDLRAP1. SNAP91 and clathrin. Reduces interaction with EPN1. No effect on EPS15 binding.
Strongly reduces interaction with SNAP91, EPN1 and clathrin. No effect on EPS15 binding. Abolishes interaction with ARRB1 and with DENND1B.
Strongly reduces interaction with SNAP91, EPS15, AMPH and BIN1 and clathrin heavy chain.
Minor effect upon interaction with HCFC1 and transcriptional activation. Loss of activity; when associated with A-297; A-298 and A-299, or with A-307 and A-310.
Minor reduction in transcriptional activation. Moderate reduction in activity; when associated with A-270 and A-271.
Minor reduction in transcriptional activation. Moderate reduction in activity; when associated with A-305 and A-306.
Minor reduction in transcriptional activation; when associated with A-295 or A-305 and A-306.
Moderately reduces interaction with HCFC1 and transcriptional activation. Loss of activity; when associated with A-273 and A-275.
No effect on transcriptional activation. Minor reduction in activity; when associated with A-270 and A-271.
Strongly reduces interaction with HCFC1 and transcriptional activation. Loss of activity; when associated with A-264 and A-265, or A-273 and A-275.
Strongly reduces interaction with HCFC1 and transcriptional activation. Loss of activity; when associated with A-297; A-298 and A-299, or with A-307 and A-310.
Ankyrin repeat domain-containing protein 27
Disrupts interaction with VPS29; when associated with A-432.
Disrupts interaction with VPS29; when associated with A-434.
Disrupts interaction with VPS29; when associated with A-712.
Disrupts interaction with VPS29; when associated with A-714.
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform
Benign variant; associated with lower plasma HDL cholesterol levels in hypercholesterolemia patients that carry a pathogenic variant in LDLR.
Found in a patient with idiopathic short stature; unknown pathological significance.
In LARS; abolishes receptor homodimerization.
In LARS; almost completely abolishes GH-binding at cell surface and in membrane fractions.
In LARS; almost completely abolishes GH-binding at cell surface: 26% binding to membrane fractions.
In LARS; almost completely abolishes GH-binding at cell surface: 53% binding to membrane fractions.
In LARS; loss of ability to bind ligand.
No change in shedding activity: No change in hormone binding.
Nuclear pore complex-interacting protein family member B6
Heterogeneous nuclear ribonucleoprotein U-like protein 2
Abolishes interaction with SPAST and VPS4A; when associated with A-188.
Abolishes interaction with SPAST and VPS4A; when associated with A-192.
Abolishes interaction with SPAST and no effect on interaction with VPS4A; when associated with R-178 and R-181.
Abolishes interaction with SPAST and no effect on interaction with VPS4A; when associated with R-181 and R-184.
Abolishes interaction with SPAScT and no effect on interaction with VPS4A; when associated with R-178 and R-184.
Reduced interaction with TOM1; when associated with Ala-12.
Reduced interaction with TOM1; when associated with Ala-20.
Reduced interaction with TOM1; when associated with Ala-23.
Reduced interaction with TOM1; when associated with Ala-9.
Loss of the ability to decrease intracellular reactive oxygen species.
28 kDa heat- and acid-stable phosphoprotein
Dipeptidyl aminopeptidase-like protein 6
In NSLH1; creates a N-myristoylation site, resulting in myristoylation of the protein and aberrant targeting to the plasma membrane.
In NSLH1; significantly decreases ERK1/2 activity; does not affect cytoplasm and nucleus localization; does not affect SHOC2-MRAS-RAF1 complex assembly; impairs interaction with phosphatase 1c.
Paired immunoglobulin-like type 2 receptor beta
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B
EF-hand calcium-binding domain-containing protein 5
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 3
Found in patients with Bardet-Biedl syndrome carrying mutations in other BBS genes; uncertain pathological role.
In a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS1; uncertain pathological role.
In a patient with Bardet-Biedl syndrome homozygous for a mutation in BBS12; uncertain pathological role.
Coiled-coil domain-containing protein 134
Reduces in vitro phosphorylation by RPS6KB1. Abolishes in vitro phosphorylation by RPS6KB1; when associated with A-385.
Reduces in vitro phosphorylation by RPS6KB1. Reduces in vitro phosphorylation by RPS6KB1; when associated with A-383.
Dehydrogenase/reductase SDR family member 13
Zinc finger and BTB domain-containing protein 49
16% of the population; infertile and fertile individuals.
Fetal and adult testis-expressed transcript protein
In CTS2; reduced secretion in tendon cells; no effect on secretion in chondrocytes; disrupted pentamerization; induced ER stress.
In EDM1 and CTS2; reduced secretion in tendon cells and chondrocytes.
In EDM1; phenotype overlapping with mild PSACH.
In EDM1; phenotypic features overlapping with mild PSACH.
In PSACH; severe form; MUT3 mutant; most common mutation; binds less calcium and causes misfolding of the protein; greatly reduced interaction with ACAN; reduced interaction with collagen.
In a patient with multiple epiphyseal dysplasia.
Abolishes ligand binding; when associated with A-142 or S-142.
Abolishes ligand binding; when associated with A-219 or S-219.
In isoform 12, isoform 14 and isoform 15.
NPxxY; plays a role in stabilizing the activated conformation of the receptor
Increases affinity for IL11RA and stimulation of cell proliferation.
Strongly increases affinity for IL11RA and stimulation of cell proliferation.
Abolishes homodimerization and interaction with CRK isoform CRK-II.
Abolishes interaction with CRK isoform CRK-II. Abolishes inhibition of CRK-II-dependent membrane ruffling.
Strongly decreases homodimerization and interaction with CRK isoform CRK-II.
Pre-rRNA-processing protein TSR2 homolog
Decreases ATPase activity. Reduces synthesis of adenosylcobalamin and methylcobalamin.
Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity.
Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity. Reduces synthesis of adenosylcobalamin and methylcobalamin.
Decreases interaction with LMBD1. Reduces synthesis of adenosylcobalamin and methylcobalamin.
Decreases of ATPase activity. Decreases cobalamin transport activity.
Does not affect ATPase activity. Does not affect cobalamin transport activity.
Does not affect ATPase nor cobalamin transport activities.
In MAHCJ; decreases interaction with LMBD1. Does not affect lysosomal subcellular location. Decreases ATPase activity.
In MAHCJ; does not affect ATPase activity. Loss of cobalamin transport activity. Decreases interaction with LMBD1. Does not affect lysosomal subcellular location.
In MAHCJ; strong decrease of ATPase activity. Strong decrease of cobalamin transport activity.
Loss of ATPase activity. Loss of cobalamin transport activity.
In KTZS; unknown pathological significance.
Found as homozygous mutation in a patient with autosomal recessive cutis laxa also carrying a mutation in FBLN5; unknown pathological significance.
In isoform 1, isoform 2, isoform 4 and isoform 5.
In isoform 1, isoform 2, isoform 5, isoform 6, isoform 7, isoform 8, isoform 10, isoform 11, isoform 12 and isoform 13.
In isoform 5, isoform 6, isoform 7, isoform 8, isoform 11 and isoform 12.
In isoform 6, isoform 7, isoform 8, isoform 11, isoform 12 and isoform 13.
Found in a patient with Dravet syndrome; unknown pathological significance.
Found in a patient with acute encephalitis with refractory and repetitive partial seizures; unknown pathological significance.
Found in a patient with acute encephalopathy with biphasic seizures, late reduced diffusion and in a patient with Dravet syndrome; unknown pathological significance.
Found in a patient with autism spectrum disorder; unknown pathological significance.
Found in a patient with non-specific acute encephalopathy; unknown pathological significance.
Found in a patient with schizofrenia; unknown pathological significance.
Found in autism; unknown pathological significance.
In BFIS3; gain of function mutation; hyperpolarizing shift of the activation curve.
In BFIS3; increased voltage-gated sodium channel activity; decreased overall channel availability during repetitive stimulation; gain of function; no effect on kinetics of activation or inactivation; no effect on voltage dependence of activation.
In BFIS3; increased voltage-gated sodium channel activity; depolarized shift of steady-state inactivation; increased persistent sodium current; slower fast inactivation; accelerated recovery of fast inactivation; gain of function.
In BFIS3; increased voltage-gated sodium channel activity; faster recovery from inactivation; gain of function.
In BFIS3; increased voltage-gated sodium channel activity; gain of function.
In BFIS3; increased voltage-gated sodium channel activity; impaired fast inactivation; no effect on kinetics of activation or inactivation; no effect on voltage dependence of activation; gain of function.
In BFIS3; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function.
In BFIS3; increased voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation; gain of function.
In BFIS3; modified voltage-gated sodium channel activity; modified voltage dependence of activation and inactivation.
In BFIS3; mutant channel inactivates more slowly than wild-type whereas the sodium channel conductance is not affected.
In BFIS3; unknown pathological significance.
In DEE11 and EA9; increased voltage-gated sodium channel activity; increased persistent sodium current; gain of function.
In DEE11 and EA9; unknown pathological significance; no effect on voltage-gated sodium channel activity; higher current density when associated with G-1882.
In DEE11; also found in patients with familial episodic ataxia and impairment of speech development.
In DEE11; hyperpolarizing shift of the activation curve and increased persitent current; gain of function.
In DEE11; increased neuronal excitability; increased peak sodium current densities; gain of function.
In DEE11; increased voltage-gated sodium channel activity; markedly altered the voltage-dependence of the channel; gain of function.
In DEE11; markedly altered channel voltage-dependence; responds to modified Atkins diet.
In DEE11; modified voltage-gated sodium channel activity; activated with lowered voltage sensitivity; disturbed fast and slow inactivation.
In DEE11; phenotype consistent with West syndrome; decreased neuronal excitability; decreased peak sodium current densities; loss of function.
In DEE11; the disease progresses to West syndrome.
In DEE11; unknown pathological significance.
In EA9; gain of function mutation resulting in increased voltage-gated sodium channel activity; hyperpolarized activation; higher current density when associated with A-1522 compared to wild-type or G-1882 alone.
In EA9; unknown pathological significance.
Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)
Probable disease-associated variant found in a boy with infantile spasms and bitemporal glucose hypometabolism.
Probable disease-associated variant found in a patient with autism spectrum disorder.
Probable disease-associated variant found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; decreased expression; loss of function.
Probable disease-associated variant found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; faster channel inactivation; fewer channels contribution to macroscopic currents and fewer channels expressed on membrane.
Probable disease-associated variant found in a patient with autism spectrum disorder; decreased voltage-gated sodium channel activity; faster channel inactivation; loss of function.
Probable disease-associated variant found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting.
Probable disease-associated variant found in a patient with autism spectrum disorder; loss of voltage-gated sodium channel activity; non-conducting; no dominant-negative effect.
Probable disease-associated variant found in a patient with drug-resistant focal epilepsy.
Probable disease-associated variant found in a patient with early-onset seizures and Rett-like features, including autistic behavior, limited hand function with chorea and profound intellectual disability.
Probable disease-associated variant found in a patient with intractable epilepsy and severe mental decline; non-conducting; loss of voltage-gated sodium channel activity; dominant-negative.
Probable disease-associated variant found in a patient with non-syndromic intellectual disability and epilepsy.
Probable disease-associated variant found in patients with GEFS+.
Sodium channel protein type 2 subunit alpha
There is no significant effects on the voltage-dependence of the channel.
In CAND; <0.5% residual enzyme activity.
In CAND; about 25% residual enzyme activity.
In CAND; pan-European origin; most prevalent among non-Jewish CAND patients; probably the most ancient mutation; loss of activity.
In CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity.
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
No effect on interaction with FYN or CSK.
No effect on interaction with FYN. Abolishes interaction with CSK.
Phosphoprotein associated with glycosphingolipid-enriched microdomains 1
Abolishes phosphorylation at Ser-47, restores deacetylation activity and inhibits DNA damage-induced apoptosis.
Blocks residue phosphorylation, restores deacetylation activity and inhibits DNA damage-induced apoptosis.
Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-47.
Greatly diminishes phosphorylation by MAPK8; when associated with A-27 and A-530.
Greatly diminishes phosphorylation by MAPK8; when associated with A-47 and A-530.
Impairs in vitro methylation by SETD7; when associated with R-233, R-235 and R-238.
Impairs in vitro methylation by SETD7; when associated with R-233, R-235a and R-236.
Impairs in vitro methylation by SETD7; when associated with R-233, R-236 and R-238.
Impairs in vitro methylation by SETD7; when associated with R-235, R-236 and R-238.
Loss of function; abolishes both protein deacetylase and decrotonylase activities. Reduces the interaction with CCAR2 and APEX1. Increases acetylation of APEX1.
Loss of interaction with the sumoylated form of CCAR2. No effect on its deacetylation activity.
NAD-dependent protein deacetylase sirtuin-1
No effect on phosphorylation (in vitro and in vivo).
Phosphothreonine; by DYRK1A, DYRK3 and MAPK8
Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-530.
Reduces in vitro phosphorylation by CDK1. Impairs cell proliferation and cell cycle progression; when associated with A-540.
Reduces in vitro phosphorylation by CaMK2; when associated with S-659. Greatly reduces in vivo phosphorylation; when associated with A-659.
Reduces in vitro phosphorylation by CaMK2; when associated with S-661. Greatly reduces in vivo phosphorylation; when associated with A-661.
Abolishes interaction with TRAF2 and TRAF3.
Abolishes interaction with TRAF2; greatly diminishes interaction with TRAF3.
Complete loss of cleavage by Seneca Valley virus protease 3C.
Diminishes interaction with TRAF2 and TRAF3.
No effect on cleavage by Seneca Valley virus protease 3C.
TRAF family member-associated NF-kappa-B activator
Does not affect function in negative regulation of PAX6 expression.
In AN3; affects function and results in increased negative regulation of PAX6 expression compared to wild-type.
Found in 1.1% of population and in some schizophrenic patients.
Gamma-aminobutyric acid receptor subunit beta-1
In DEE45; no effect on localization to the plasma membrane; increased GABA-gated chloride ion channel activity; increased single channel burst duration.
Abolishes phosphorylation by BRSK2. Abolishes effect on insulin secretion.
Constitutively activated, due to loss of an inhibitory phosphorylation site. Increases interaction with CCNY.
Loss of kinase activity. Abolishes effect on insulin secretion.
High sensitivity to androstenone and androstadienone.
Impaired response to androstenone and androstadienone.
Impaired response to androstenone and androstadienone; when associated with M-133.
Impaired response to androstenone and androstadienone; when associated with W-88.
In DEE14; unknown pathological significance.
In DEE14; variant homologue in rat has increased channel activity upon positive potentials.
In allele CYP4B1*2, allele CYP4B1*7 and allele CYP4B1*5.
Sodium-dependent phosphate transport protein 2B
Ral GTPase-activating protein subunit alpha-2
Suppressor APC domain-containing protein 2
Rare variant; may act as a phenotype modifier in EIEE13 patients carrying SCN8A mutations.
In PC1; requires 2 nucleotide substitutions.
Rare variant; found as somatic mutation in a patient with localized epidermolytic hyperkeratosis in the right palm and the right sole; unknown pathological significance.
Zinc finger CCHC-type and RNA-binding motif-containing protein 1
Found in a patient with Leigh syndrome; unknown pathological significance; decrease in enzyme activity.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial
Likely benign variant; associated with beta-glucuronidase pseudodeficiency with no clinical consequences; reduced activity levels.
Janus kinase and microtubule-interacting protein 2
Large neutral amino acids transporter small subunit 2
In DRTA2; disruption of V-ATPase assembly resulting in loss of enzyme activity; impaired trafficking of V-ATPase to apical cell membrane; impaired renal proton secretion.
Loss of interactions with SLC9A3R1 and SCL4A7.
V-type proton ATPase subunit B, kidney isoform
Abolished serine/threonine-protein kinase activity.
Loss of phosphorylation; abolished inhibition of activity, leading to constitutively active.
Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3
Prevents the phosphorylation of phosphate-primed glycogen synthase.
Reduces tail-anchored proteins transfer.
Small glutamine-rich tetratricopeptide repeat-containing protein alpha
4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT5
Decreases both alpha-(1,3)-fucosyltransferase and alpha-(1,4)-fucosyltransferase activity of 50%.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L- and 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with T-101; H-105; K-111 and T-118.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L- and 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with T-101; H-105; R-110 and K-111.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L- and 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with T-101; H-105; R-110 and T-118.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L- and 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with T-101; R-110; K-111 and T-118.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L- and 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated withH-105; R-110; K-111 and T-118.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity with type 2 oligosaccharide acceptor; when associated with I-87 and S-92. Increases significantly 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity with type 1 oligosaccharide acceptors; when associated with I-87 and S-92. Decreases of 50% the 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity with type 2 glycolipid nLc4Cer; when associated with I-87 and S-92. Increases significantly the 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity with type 1 glycolipid Lc4Cer; when associated with I-87 and S-92.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; when associated with H-86 and I-87. Increases significantly 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with H-86 and I-87. Decreases of 50% the 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity with type 2 glycolipid nLc4Cer; when associated with H-86 and I-87. Increases significantly the 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity with type 1 glycolipid Lc4Cer; when associated with H-86 and I-87.
Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; when associated with H-86 and S-92. Increases significantly 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; when associated with H-86 and S-92. Decreases of 50% the 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity with type 2 glycolipid nLc4Cer; when associated with H-86 and S-92. Increases significantly the 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity with type 1 glycolipid Lc4Cer; when associated with H-86 and S-92.
Does not affect alpha-(1,3)-fucosyltransferase activity. Loss of alpha-(1,4)-fucosyltransferase activity.
Increases alpha-(1,3)-fucosyltransferase activity. Loss of alpha-(1,4)-fucosyltransferase activity. Loss of site-specific fucosylation; when associated with E-125 and V-126. Reverses the preferential fucosylation properties leading to production of 72% of sialyl-lewis x; when associated with K-87; E-125 and V-126. Significantly decreases to cell-surface expression of VIM2 antigen; when associated with K-87; E-125 and V-126.
Loss of site-specific fucosylation; when associated with R-124 and E-125. Reverses the preferential fucosylation properties leading to production of 72% of sialyl-lewis x; when associated with K-87; R-124 and E-125. Significantly decreases to cell-surface expression of VIM2 antigen; when associated with K-87; R-124 and E-125.
Loss of site-specific fucosylation; when associated with R-124 and V-126. Reverses the preferential fucosylation properties leading to production of 72% of sialyl-lewis x; when associated with K-87; R-124 and V-126. Significantly decreases to cell-surface expression of VIM2 antigen; when associated with K-87; R-124 and V-126.
Reverses the preferential fucosylation properties leading to production of 72% of sialyl-lewis x; when associated with R-124; E-125 and V-126. Significantly decreases cell-surface expression of VIM2 antigen; when associated with R-124; E-125 and V-126.
Abolishes localization to cytoplasmic vesicles in case of infection by S.typhimurium.
Does not affect localization to cytoplasmic vesicles in case of infection by S.typhimurium.
Doublecortin domain-containing protein 2
In DFNB66; results in ciliary abnormalities including increased ciliary length.
In NSC; loss of localization to the cilium axoneme.
Abolishes activity. Abolishes checkpoint recovery.
Abolishes interaction with CDC25C and reduces centrosomal localization.
D-box that targets the protein for proteasomal degradation in anaphase
In analog-sensitive mutant; enlarged catalytic pocket to accommodate purine analogs; when associated with G-130.
In analog-sensitive mutant; enlarged catalytic pocket to accommodate purine analogs; when associated with V-67.
In pincer mutant; loss of centrosomal location and decreased interaction with phosphorylated CDC25C and BUB1; when associated with A-538.
In pincer mutant; loss of centrosomal location and decreased interaction with phosphorylated CDC25C and BUB1; when associated with M-540.
Increases activity and restores recovery after DNA damage checkpoint.
Increases activity. Results in a block in G1/S.
Interferes with ubiquitination and subsequent proteasomal degradation in anaphase; when associated with A-337.
Interferes with ubiquitination and subsequent proteasomal degradation in anaphase; when associated with A-340.
Loss of centrosomal localization and of S-phase progression; when associated with A- 414 and A-427.
Loss of kinase activity. No effect on RIOK2-binding.
Loss of kinase activity. No effect on S-phase progression.
No change in activity. Increases activity and restores recovery after DNA damage checkpoint; when associated with D-210.
No effect on centrosomal localization, nor on S-phase progression; when asscociated with A-427. Loss of centrosomal localization and of S-phase progression; when associated with A- 415 and A-427.
No effect on centrosomal localization, nor on S-phase progression; when associated with A-414. Loss of centrosomal localization and of S-phase progression; when associated with A- 414 and A-415.
Reduced catalytic activity, but no effect on affinity for ATP.
Severe mitotic defects leading to prometaphase delay. Increased localization at kinetochores leading to increased levels of phosphorylated BUBR1.
Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
In SCAR2; impairs cleavage of FXN; does not impair cleavage of DLD, NFS1 and PRDX3.
Mitochondrial-processing peptidase subunit alpha
Ras GTPase-activating protein-binding protein 2
Abolishes localization to lipid droplets.
Abrogates ATP hydrolysis, abolishes microtubule severing, stabilizes the homohexameric form, and promotes microtubule binding and redistribution from the endosome to microtubules.
Abrogates ATPase activity and abolishes microtubule severing.
Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin and abolishes microtubule severing.
Abrogates binding to the tail of alpha-tubulin and beta-3-tubulin, impairs ATPase activity and abolishes microtubule severing.
Acts as a disease modifier; patients carrying a mutated allele of spastin and L-44 on the other allele are affected by severe spastic paraplegia with an early age of onset; may decrease the activity of the alternative promoter which directs the synthesis of isoform 3 and isoform 4.
Acts as a disease modifier; patients carrying a mutated allele of spastin and Q-45 on the other allele are affected by severe spastic paraplegia with an early age of onset.
Does not affect localization to lipid droplets.
Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-120.
Impairs binding to CHMP1B. Impairs midbody localization; when associated with D-124.
In SPG4; abrogates ATPase activity and promotes microtubule binding.
In SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles and impairs traffic from the ER to Golgi.
In SPG4; abrogates ATPase activity, promotes microtubule binding and the formation of thick microtubule bundles.
In SPG4; abrogates binding to the tail of beta-3-tubulin, abolishes microtubule severing and promotes the formation of thick microtubule bundles.
In SPG4; promotes microtubule binding and the formation of thick microtubule bundles.
In SPG4; requires 2 nucleotide substitutions.
In SPG4; unknown pathological significance.
In SPG4; variant form with congenital arachnoid cysts.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in UFM1)
Abolishes BRCA1 interaction and ubiquitination. No activation of CHEK1 after DNA damage.
Abolishes damage recruitment capability.
Decreased CUL3/KLHL15-mediated proteasomal degradation.
Decreased PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-276.
Decreased interaction with KLHL15, decreased polyubiquitination and CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-end resection activity.
Impaired FZR1-binding and APC/C-mediated polyubiquitination. Increased stability. No effect on MRE11-binding, nor on CUL3/KLHL15-mediated proteasomal degradation. No effect on DNA-en resection activity.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-115; R-132 and R-133.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-760.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-760 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-759; R-760 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-572; R-640; R-759; R-760 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-404; R-578; R-640; R-759; R-760 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-132; R-133; R-572; R-578; R-640; R-759; R-760 and R-782.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-132.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-115 and R-133.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-62; R-78; R-132 and R-133.
In K12R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132; R-133; R-404; R-572; R-578; R-640; R-759; R-760 and R-782. In K5R; defects in ability to promoting DNA resection and homologous recombination; when associated with R-78; R-115; R-132 and R-133.
No effect on CUL3/KLHL15-mediated proteasomal degradation.
No effect on KLHL15-binding, nor on CUL3/KLHL15-mediated proteasomal degradation.
No effect on PIN1-binding. Impaired PIN1-binding, partially decreased CUL3/KLHL15-mediated proteasomal degradation, no effect on BRCA1-, MRE11-, nor on KLHL15-binding; when associated with A-315.
No effect on RPA focus formation on DNA damage.
Transforming growth factor-beta receptor type 3-like protein
In DFNB9 and AUNB1; temperature sensitive AUNB1 phenotype with severe hearing loss during febrile illness.
Alpha-ketoglutarate dehydrogenase component 4
In MASNS; decreased basal PKA enzymatic activity in lysates from transfected cells.
In MASNS; unknown pathological significance; requires 2 nucleotide substitutions; decreased basal PKA enzymatic activity in lysates from transfected cells.
cAMP-dependent protein kinase type I-beta regulatory subunit
Locates in the nucleus and cytosol. No interaction with RABGGTB.
Aspartate 1-(chondroitin 4-sulfate)-ester
Inter-alpha-trypsin inhibitor heavy chain H2
In NKH; decreased aminomethyltransferase activity.
In NKH; loss of aminomethyltransferase activity.
Loss of aminomethyltransferase activity.
Leucyl-cystinyl aminopeptidase, pregnancy serum form
Abolishes interaction with CDC42 and induces a decrease in blocking CDC42-induced JNK activation; when associated with A-62.
Abolishes interaction with CDC42 and induces a decrease in blocking CDC42-induced JNK activation; when associated with A-66.
Abolishes interaction with CDC42, induces a decrease in blocking CDC42-induced JNK activation but does not affect targeting to the activated TCR; when associated with A-33 and A-38.
Abolishes interaction with CDC42, induces a decrease in blocking CDC42-induced JNK activation but does not affect targeting to the activated TCR; when associated with A-33 and A-41.
Abolishes interaction with CDC42, induces a decrease in blocking CDC42-induced JNK activation but does not affect targeting to the activated TCR; when associated with A-38 and A-41.
Prevents targeting to the activated TCR.
Abolishes localization to the nuclear membrane.
In EPM1B; affects interaction with REST.
Disrupts interaction with VIPAS39; no effect on interaction with STX7; impairs localization to VIPAS39-containing endosomal compartment.
In ARCS1; effect on interaction with VIPAS39 is reported conflictingly but disrupts colocalization with VIPAS39 at cytoplasmic organelle; impairs localization to VIPAS39-containing endosomal compartment; and induces fragmentation of the VIPAS39-containing endosomal compartment; no effect on interaction with STX7 and association with the HOPS complex.
In ARCS1; no effect on interaction with VIPAS39; impairs localization to VIPAS39-containing endosomal compartment.
No effect on interaction with VIPAS39 and STX7; impairs localization to VIPAS39-containing endosomal compartment.
No effect on interaction with VIPAS39; no effect on interaction with STX7 and association with the HOPS complex; impairs localization to VIPAS39-containing endosomal compartment.
Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-382 and E-511.
Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-382 and E-517.
Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-133; E-511 and E-517.
Reduces phosphorylation activity, but does not impair phagolysosomal fusion in M.tuberculosis-infected macrophages; when associated with E-382; E-511 and E-517.
Vacuolar protein sorting-associated protein 33B
Mediator of RNA polymerase II transcription subunit 16
Glycosyltransferase 1 domain-containing protein 1
Decreased protein interaction with HCV NS5A.
Increased protein interaction with HCV NS5A.
Protein kinase C and casein kinase substrate in neurons protein 2
Does not affect cAMP biosynthetic process in response to C5 alpha chain stimulation. Reduces by 40?60% cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation.
Does not affect cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation. Reduces by 40% cAMP biosynthetic process in response to C5 alpha chain stimulation.
Reduces cAMP biosynthetic process in response to C5 alpha chain stimulation and more severely in response to sphingosine 1-phosphate stimulation.
Found in an individual with overgrowth, learning disability and dysmorphic features; unknown pathological significance.
Loss of function in RIG-I signaling pathway; when associated with A-21.
Loss of function in RIG-I signaling pathway; when associated with A-24.
Prevents degradation by hepatitis C virus NS3/NS4A.
T-cell surface glycoprotein CD3 epsilon chain
Protein tyrosine phosphatase receptor type C-associated protein
Mediator of RNA polymerase II transcription subunit 30
Increased ability to bind DAG, no effect on phorbol-ester binding.
No effect on ability to bind phorbol ester, increase in ability to bind DAG.
No effect on ability to bind phorbol ester, loss of ability to bind DAG, reduced DAG-induced membrane translocation.
Slight increase in ability to bind DAG, no effect on phorbol-ester binding.
Slight loss in ability to bind DAG and phorbol-ester.
Slight loss in ability to bind DAG and phorbol-ester; when associated with A-156.
Slight loss in ability to bind DAG and phorbol-ester; when associated with F-158.
Upstream-binding factor 1-like protein 1
Sphingomyelin synthase-related protein 1
Abolishes 2-oxoglutarate-binding and enzyme activity.
Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6
Decreases interaction with the NET domain of BRD4.
Impairs both hydroxylation activity and 2-oxoglutarate turnover assays.
Impairs enzyme activity and 2-oxoglutarate-binding.
Impairs enzyme activity without affecting 2-oxoglutarate-binding.
Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-187 and A-189.
Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-187 and A-273.
Loss of histone arginine demethylase and lysyl-hydroxylase activities. Abolishes homooligomerisation. Loss of arginine demethylase and a lysyl-hydroxylase activities; when associated with A-189 and A-273.
Nearly abolishes the interaction with the NET domain of BRD4.
HEAT repeat-containing protein 1, N-terminally processed
N-acetylthreonine; in HEAT repeat-containing protein 1, N-terminally processed
10-fold decrease in activity; when associated with Y-971.
10-fold decrease in activity; when associated with Y-972.
Decreased activity. Loss of activity; when associated with D-1320.
Decreased activity. Loss of activity; when associated with D-1709.
Decreased activity. Loss of activity; when associated with E-1444.
Decreased activity. Loss of activity; when associated with E-1813.
Found in Wilms tumor from a patient with GLOW syndrome; somatic mutation; unknown pathological significance.
In non-epithelial ovarian tumor; somatic mutation.
In non-epithelial ovarian tumor; somatic mutation; results in reduced RNase IIIb activity but retention of RNase IIIa activity.
Secretory carrier-associated membrane protein 4
In CILD20; expressed at very low levels in patients' nasal epithelial cells; the genetic variation producing this missense variant predominantly affects splicing.
Outer dynein arm-docking complex subunit 1
GDP-fucose protein O-fucosyltransferase 2
No enhanced secretion of ADASMTS13; when associated with A-396.
Reduces enzyme activity. No enhanced secretion of ADASMTS13; when associated with A-396.
Zinc finger and SCAN domain-containing protein 21
Abolishes membrane remodeling capacity; no effect on dimerization.
Abolishes phosphatidylinositol phosphate binding. Abolishes endosomal location.
No effect on membrane remodeling and membrane binding; when associated with A-442.
No effect on membrane remodeling and membrane binding; when associated with A-445.
No effect on the transcriptional activity of the reconstituted TFIIH complex.
Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein
Abolishes interaction with monoubiquitinated FANCD2; when associated with A-44.
Abolishes interaction with monoubiquitinated FANCD2; when associated with A-47.
In KMIN; partially complement cell survival upon exposure to mitomycin C.
Loss of nuclease activity. Loss of nuclease activity; when associated with A-864; A-975 and A-977.
Loss of nuclease activity; when associated with A-864; A-960 and A-975.
Loss of nuclease activity; when associated with A-864; A-960 and A-977.
Loss of nuclease activity; when associated with A-960; A-975 and A-977.
Still localized to sites of DNA damage but the strength of the signal is diminished.
Strongly reduced affinity for sites that have a 5'-terminal phosphate anchor at a flap of 1 nucleotide; when associated with A-706.
Strongly reduced affinity for sites that have a 5'-terminal phosphate anchor at a flap of 1 nucleotide; when associated with A-952.
45% decreased binding to microtubules. Decreased polyglutamylase activity. 76% decreased binding to microtubules; when associated with 425-E--E-427.
76% decreased binding to microtubules; when associated with 385-E--E-393.
Nearly abolished polyglutamylase activity.
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1
In SCAR11; shows intracellular localization different from that of the wild-type protein; forms a reticular pattern in the cytoplasm; does not show submembranous distribution; is abnormally retained in the endoplasmic reticulum consistent to improper folding.
39S ribosomal protein L43, mitochondrial
von Willebrand factor C and EGF domain-containing protein
Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7
Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K7
Abolishes ability to suppress pre-let-7 biogenesis and localization to P-bodies without affecting pre-let-7 binding; when associated with A-147.
Abolishes ability to suppress pre-let-7 biogenesis and localization to P-bodies without affecting pre-let-7 binding; when associated with A-169.
Does not affect localization to P-bodies; when associated with A-46 and A-55.
Does not affect localization to P-bodies; when associated with A-46 and A-73.
Does not affect localization to P-bodies; when associated with A-55 and A-73.
In FIGLU-URIA; mild phenotype; decreased glutamate formimidoyltransferase activity; 57% wild-type activity.
In FIGLU-URIA; mild phenotype; decreased glutamate formimidoyltransferase activity; 61% of wild-type activity.
Leucine-rich repeat-containing protein 59
Leucine-rich repeat-containing protein 59, N-terminally processed
N-acetylthreonine; in Leucine-rich repeat-containing protein 59, N-terminally processed
Abolishes adenylyltransferase activity; when associated with A-216.
Abolishes adenylyltransferase activity; when associated with A-218.
Reduced terminal uridylyltransferase activity; when associated with A-779.
Reduced terminal uridylyltransferase activity; when associated with A-783.
Speckle targeted PIP5K1A-regulated poly(A) polymerase
Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-142, R-230 and R-244.
Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-220, R-230 and R-244.
Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-230.
Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-244.
Reduced affinity for all nucleotides, but with preferential binding of GDP over GTP.
No effect on interaction with CCDC22, CCDC93, VPS26C and VPS35L.
Slightly decreases interaction with CCDC22, CCDC93, VPS26C and VPS35L.
Strongly decreases interaction with CCDC22, CCDC93, VPS26C and VPS35L. No effect on endosomal location.
Coiled-coil domain-containing protein 146
In a breast pleomorphic lobular carcinoma sample; somatic mutation.
In an ovarian endometrioid cancer sample; somatic mutation.
Mitogen-activated protein kinase kinase kinase 6
Beta-crystallin A3, isoform A1, Delta4 form
Beta-crystallin A3, isoform A1, Delta7 form
Beta-crystallin A3, isoform A1, Delta8 form
In ECO; significantly impairs kinase activity; decreased localization at the ciliary tips; impaired ciliogenesis; results in abnormally elongated cilia; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system; loss of nuclear localization.
In EJM10; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system.
In EJM10; unknown pathological significance.
In EJM10; unknown pathological significance; impairs mitosis, cell-cycle exit and radial neuroblast migration, while promoting apoptosis, when tested in a heterologous system.
Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-36.
Loss of activity and autophosphorylation; when associated with R-33; R-34 and R-38.
Loss of activity and autophosphorylation; when associated with R-33; R-36 and R-38.
Loss of activity and autophosphorylation; when associated with R-34; R-36 and R-38.
Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with A-157.
Reduction of activity and loss of autophosphorylation. Loss of activity and autophosphorylation; when associated with F-159.
Zinc finger and SCAN domain-containing protein 20
Found in patients with mild intellectual disability; unknown pathological significance.
Impairs effect on cell proliferation; when associated with A-20.
Impairs effect on cell proliferation; when associated with A-340.
Testis-specific Y-encoded-like protein 2
In SPG72; abolishes REEP2 interaction with membranes; affects correct shaping of the endoplasmic reticulum.
In SPG72; reduces REEP2 interaction with membranes; affects correct shaping of the endoplasmic reticulum.
Abolishes inactivation by phosphorylation; when associated with A-232 and A-293.
Abolishes inactivation by phosphorylation; when associated with A-293 and A-300.
In PDHAD; affects mitochondrial import of precursor protein.
In PDHAD; loss of activity; common mutation.
Phosphoserine; by PDK1, PDK2, PDK3 and PDK4
Probable disease-associated variant found in a patient with moderate developmental delay, mild dysmorphism and mildly elevated serum lactate.
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Reduces enzyme activity. Abolishes inactivation by phosphorylation; when associated with A-232 and A-300.
Pleckstrin homology-like domain family A member 2
Lymphocyte antigen 6 complex locus protein G5b
Abolishes PKA-mediated phosphorylation; no effect on caspase-mediated cleavage.
Abolishes PKC-mediated phosphorylation; no effect on PKA-mediated phosphorylation.
Abolishes gamma-secretase activity. Reduces production of amyloid-beta in APP processing. Accumulation of full-length PS1. Loss of binding of transition state analog gamma-secretase inhibitor.
Alters gamma-secretase cleavage specificity. Increased production of amyloid-beta protein 42. No effect on enzymatic activity.
Decreased protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Formation of an artifactual disulfide bond with a substrate protein.
Greatly reduced endoproteolytic cleavage. Very little APP and NOTCH1 processing. Very low levels of amyloid-beta protein 40 and no detectable amyloid-beta protein 42.
In AD3; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production.
In AD3; abolishes protease activity with APP.
In AD3; abolishes protease activity with APP; decreased activity for Notch cleavage.
In AD3; affects APP processing resulting in increased amyloid-beta 42/amyloid-beta 40 ratio; does not affect NOTCH processing; does not affect endoproteolysis; reduced interaction with PEN2; results in decreased protein levels in the endoplasmic reticulum but increased levels in early endosome; reduced ability to maintain ER calcium homeostasis.
In AD3; also found in late-onset Alzheimer disease; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; no effect on interaction with GFAP.
In AD3; atypical phenotype presenting as language impairment, impaired frontal executive function and relative preservation of memory; severe decrease of APP and Notch proteolysis.
In AD3; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1.
In AD3; decreased protease activity with APP; no effect on interaction with GFAP.
In AD3; decreased protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; disease phenotype includes spastic paraparesis; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production.
In AD3; disease phenotype includes spastic paraparesis; unknown pathological significance; severe decrease of protease activity with APP; results in decreased amyloid-beta 42 and amyloid-beta 40 production.
In AD3; disease phenotype shows high clinical variability; founder mutation originating from Southern Italy and distributed worldwide; alters the conformation of the active site; slightly increased protease activity with APP; decreased activity for Notch1 cleavage; no loss of its ability to cleave Ephb2/CTF1.
In AD3; impaired ability to cleave Ephb2/CTF1; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth.
In AD3; impaired protease activity with APP and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; impaired protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; increases protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; loss of function as calcium-leak channel; results in calcium overload in the endoplasmic reticulum.
In AD3; loss of protease activity with APP.
In AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1.
In AD3; nearly abolishes protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; no loss of its ability to cleave Ephb2/CTF1.
In AD3; onset in adolescence; severe decrease of protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; results in reduced Notch proteolysis.
In AD3; partially abolishes gamma-secretase activity; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; reduced APP cleavage resulting in decreased amyloid-beta 42 and amyloid-beta 40 production; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; impaired regulation of neurite outgrowth.
In AD3; results in reduced APP and Notch proteolysis.
In AD3; results in reduced APP and Notch proteolysis; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; severe decrease of protease activity with APP.
In AD3; slightly decreased protease activity with APP and slightly decreased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; slightly decreased protease activity with APP resulting in altered amyloid-beta production and mildly increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; slightly increased protease activity with APP and slightly increased amyloid-beta 42 production.
In AD3; some AD3 patients manifest spastic paraparesis and unusual amyloid plaques with prominent amyloid angiopathy on brain biopsy; decreased protease activity with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; impaired ability to cleave Ephb2/CTF1.
In AD3; strong deposition of amyloid-beta 42 is observed in brain regions of AD3 patients; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; decreased activity for Notch1 cleavage.
In AD3; the patient also manifest spastic paraparesis and apraxia; loss of protease activity with APP in vitro; altered amyloid-beta production in cells transfected with the mutant and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; uncertain pathological significance; loss of protease activity with APP.
In AD3; unknown pathological significance.
In AD3; unknown pathological significance; abolishes protease activity with APP resulting in decreased amyloid-beta 42 and amyloid-beta 40 production.
In AD3; unknown pathological significance; abolishes protease activity with APP.
In AD3; unknown pathological significance; decreased protease activity with APP.
In AD3; unknown pathological significance; decreased protease activity with APP; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; nearly abolishes protease activity with APP.
In AD3; unknown pathological significance; no significant change of protease activity with APP.
In AD3; unknown pathological significance; reduced protease activity with APP resulting in reduced amyloid-beta 40 levels but no relevant changes in amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; reduced protease activity with APP; no relevant change in amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; results in decreased protease activity with APP and decreased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; slightly decreased protease activity with APP.
In AD3; unknown pathological significance; slightly increased protease activity with APP and slightly increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; unknown pathological significance; slightly reduced protease activity with APP.
In AD3; unusual amyloid cotton wool plaques detected in one patient's brain; severe decrease of protease activity with APP; results in increased amyloid-beta 42/amyloid-beta 40 ratio.
In AD3; with unusual amyloid cotton wool plaques; almost abolishes gamma-secretase activity; no endoproteolytic cleavage; no APP nor NOTCH1 processing; no detectable amyloid-beta.
In AD3; with unusual amyloid cotton wool plaques; decreased protease activity with APP resulting in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
In CMD1U; results in slightly decreased protease activity with APP and slightly decreased amyloid-beta 42/amyloid-beta 40 ratio.
In PIDB and AD3; neuropathologic examination of brain sections from the patient shows the presence of Pick bodies and absence of beta-amyloid plaques; unknown pathological significance; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Increases production of amyloid-beta in APP processing.
Inhibits caspase-mediated cleavage. Modulates progression of apoptosis.
Loss of endoproteolytic cleavage. Severe decrease of protease activity with APP. Reduces production of amyloid-beta. Loss of NOTCH1 cleavage. Disassembly of the N-cadherin/PS1 complex at the cell surface. Impairs CDH2 processing.
Loss of endoproteolytic cleavage. Severe decrease of protease activity with APP. Reduces production of amyloid-beta. Reduces production of NICD in NOTCH1 processing.
Nearly abolishes protease activity with APP.
Nearly abolishes protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing.
No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Reduced amyloid-beta protein 42/40 ratio.
No effect on endoproteolytic cleavage. No effect on APP nor NOTCH1 processing. Slightly increased amyloid-beta protein 42/40 ratio.
No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Greatly reduced amyloid-beta protein 42/40 ratio.
No effect on endoproteolytic cleavage. No effect on APP processing. Impaired NOTCH1 processing. Some increase in amyloid-beta protein 42/40 ratio.
No endoproteolytic cleavage. No APP nor NOTCH1 processing. No detectable amyloid-beta.
No endoproteolytic cleavage; no APP, nor NOTCH1 processing. No detectable amyloid-beta.
No significant change of protease activity with APP.
Probable disease-associated variant found in a patient with dementia.
Probable disease-associated variant found in patients with late-onset Alzheimer disease; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio.
Reduces production of NICD in NOTCH1 processing.
Severe decrease of protease activity with APP.
Severe decrease of protease activity with APP. Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro.
Slightly increased protease activity with APP.
Some loss of endoproteolytic cleavage. Some loss of APP and NOTCH1 processing. 6 to 13-fold increase in amyloid-beta protein 42/40 ratio.
Very little endoproteolysis. Little APP processing. No NOTCH1 processing. Very low levels amyloid-beta protein 40 and no detectable amyloid-beta protein 42.
In RTSC4; reduced inhibition of dendrite development in transfected primary neurons; decreased interaction with MAP2; decreased interaction with TUBB3.
TATA box-binding protein-associated factor RNA polymerase I subunit A
Scavenger receptor cysteine-rich domain-containing group B protein
In NPCA3; unknown pathological significance.
Macrophage-stimulating protein receptor alpha chain
Macrophage-stimulating protein receptor beta chain
TRAF-interacting protein with FHA domain-containing protein B
Does not affect insulin-stimulated lipid kinase activity.
In SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling.
In SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling.
In a patient with severe insulin resistance; lower insulin-stimulated lipid kinase activity compared with wild-type.
Phosphatidylinositol 3-kinase regulatory subunit alpha
Found in a patient with schizophrenia; unknown pathological significance.
In DEE101; loss of function in calcium ion transmembrane import into cytosol.
In NDHMSD; changed localization to the cell membrane; decreased glutamate-gated calcium ion channel activity.
In NDHMSD; changed localization to the cell membrane; loss of glutamate-gated calcium ion channel activity.
In NDHMSD; decreased glutamate-gated calcium ion channel activity.
In NDHMSD; decreased localization to the plasma membrane of GRIN1/GRIN2B NMDA receptor complexes; changed glutamate-gated calcium ion channel activity; decreased activation by glutamate and glycine; decreased sensitivity to magnesium block; loss of function in calcium ion transmembrane import into cytosol.
In NDHMSD; loss of function in calcium ion transmembrane import into cytosol.
In NDHMSD; loss of glutamate-gated calcium ion channel activity.
In NDHMSD; no effect on glutamate-gated calcium ion channel activity.
In NDHMSD; there is near abolition of the activity of the NMDA receptor in Xenopus oocytes; alters the 3-dimensional structure at the receptor's channel pore entrance.
In NDHMSD; this mutation produces a significant increase in NMDA receptor-induced calcium currents; excessive calcium influx through NMDA receptor could lead to excitotoxic neuronal cell damage.
In NDHMSD; unknown pathological significance.
In NDHMSD; unknown pathological significance; no effect on glutamate-gated calcium ion channel activity.
In NDHMSR; changed glutamate-gated calcium ion channel activity; increased inhibition by zinc.
In NDHMSR; unknown pathological significance.
Slight decrease in glycine agonist potency; no effect on glutamate agonist potency.
EGF-containing fibulin-like extracellular matrix protein 2
In ARCL1B; does not affect secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1, highly glycosylated form of LOX and LTBP1; Does not affect interaction with LOX when LOX is non-glycosylated; proteolyzed by PLG.
In ARCL1B; increased N-glycosylation; introduced an extra O-glycosylation site; does not affect secretion; decreased elastic fiber assembly; decreased interaction with collagen type IV trimer, FBN1, ELN, LTBP1, LOXL1 and LOXL2; new fragments proteolyzed by ELANE.
In ARCL1B; loss of protein expression in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; loss of protein expression; strongly decreased secretion.
In ARCL1B; slightly decreased protein abundance in patient dermal fibroblasts; increased transforming growth factor beta receptor signaling pathway in patient fibroblasts; strongly decreased secretion; decreased elastic fiber assembly; loss of interaction with collagen type IV trimer, FBN1 and LTBP1; decreased interaction with LOXL2; new fragments proteolyzed by ELANE; new one fragment proteolyzed by MMP2.
Has a mild effect on polysaccharides binding.
In allele CLEC18A-1; abolishes binding to polysaccharides.
Fibronectin type III domain-containing protein 9
Completely abolishes hyaluronan synthase activity. Cumulates at plasma membrane.
Completely abolishes hyaluronan synthase activity. Not detected in cytoplasmic vesicles nor at cell membrane. Inability to travel from ER to Golgi. Unresponsive to AMPK-mediated inactivation.
Increases protein degradation. Abolishes hyaluronan synthase activity. Does not affect subcellular location.
Prevents O-GlcNAcylation. Increases protein stability. Reduces hyaluronan synthase activity.
Abolishes steric hindrance that traps the essential Q-69 in an unreactive position, and causes slow GTP hydrolysis in wild-type. Loss of one hydrogen bond with the gamma phosphate group of bound GTP.
Blocks DNA replication; when associated with L-69.
Has low binding affinity for GTP and GDP. Almost completely abolishes interaction with BIRC5.
Has low binding affinity for GTP and GDP. Decreases nuclear import of proteins and RNA. Stabilizes the interaction with RCC1. No effect on nuclear location during interphase. Loss of activity in triggering microtubule assembly at mitotic chromosomes.
Loss of normal mitotic chromosome segregation and defective mitotic spindle orientation.
Loss of normal mitotic chromosome segregation and formation of sister chromatid bridges.
Mimics acetylation; enhances the nuclear export of RELA/p65.
Minor effect on the interaction with the alpha phosphate group of bound GTP.
No effect on GTPase activity. Abolishes interaction with RANBP1.
Probable loss of interaction with NUTF2. Loss of transport to the nucleus.
Strongly decreased GTPase activity. Probably locked in the GTP-bound form. Loss of interaction with NUTF2. Decreases nuclear location and leads to cytoplasmic location during interphase. Loss of function in importin-mediated protein nuclear import. High activity in triggering microtubule assembly at mitotic chromosomes. Blocks DNA replication; when associated with V-19.
Strongly decreases the relase of bound GDP.
Unable to hydrolyze GTP. Increases binding to BIRC5 and promotes exaggerated spindle formation.
Single-pass membrane and coiled-coil domain-containing protein 2
H/ACA ribonucleoprotein complex subunit DKC1
In DKCX and HHS; increases interaction with SHQ1.
In DKCX; decreases interaction with SHQ1.
In DKCX; due to a 2 nucleotide inversion.
In DKCX; increases interaction with SHQ1.
In DKCX; requires 2 nucleotide substitutions.
In DKCX; results in mislocalization of the telomerase complex without affecting telomerase activity.
In HHS; increases interaction with SHQ1.
In HHS; no effect on interaction with SHQ1.
Abolishes interaction with Clostridium perfringens CPE.
Decreases interaction with Clostridium perfringens CPE.
No effect on interaction with Clostridium perfringens CPE.
Strongly decreases interaction with Clostridium perfringens CPE.
E3 ubiquitin-protein ligase pellino homolog 3
Associated with susceptibility to alcoholism.
Fails to form a PRC2.1 dimer. Reduced H3K27me3 enrichment on PRC2 target genes.
Fails to interact with JARID2; when associated with A-86.
Fails to interact with JARID2; when associated with A-90.
Fails to interact with PHF19. The PRC2.1 dimer forms but is unstable.
In IMMAS; decreased trimethylation of 'Lys-27' of histone H3; no effect on interaction with EZH2.
In IMMAS; unknown pathological significance.
No effect on interaction with PHF19. The PRC2.1 dimer forms but is unstable.
In HYC2; unknown pathological significance.
Schiff-base intermediate with dihydroxyacetone-P
GTP cyclohydrolase 1 feedback regulatory protein
Cyclic AMP-responsive element-binding protein 3-like protein 2
Processed cyclic AMP-responsive element-binding protein 3-like protein 2
Epidermal growth factor receptor kinase substrate 8-like protein 2
Cytosolic Fe-S cluster assembly factor NUBP1
N6,N6,N6-trimethyllysine; by METTL21A; in vitro
Abolishes both enzymatic activity and effects on cell proliferation.
Ubiquitin carboxyl-terminal hydrolase 17
Impaired binding to histone H3K4me3 and H3R8me2a and impaired ability to activate the Wnt signaling pathway.
Impaired binding to histone H3K4me3 and H3R8me2a and impaired ability to activate the Wnt signaling pathway. Impaired ability to activate expression of pre-rRNA.
Impaired binding to histone H3K4me3 and H3R8me2a.
28S ribosomal protein S33, mitochondrial
Defective of TEN1 binding; when associated with Ala-164 or Ala-167.
Defective of TEN1 binding; when associated with Ala-78.
Abolishes acetylation; when associated with R-117 and R-120.
Abolishes acetylation; when associated with R-117 and R-125.
Abolishes acetylation; when associated with R-120 and R-125.
Abolishes interaction with and repression of CEBPA and inhibition of adipogenesis.
Abrogates in vitro phosphorylation by CHEK2 and CHEK2-dependent stabilization of E2F1 upon DNA damage.
Decreased phosphorylation by GSK3B, leading to abolished interaction with USP11 and subsequent deubiquitination.
No retinoblastoma protein binding. No effect on interaction with and repression of CEBPA.
In CAMRQ4; abolishes ATPase activity. No effect on interaction with TMEM30A.
In CAMRQ4; unknown pathological significance.
In CAMRQ4; unknown pathological significance; abolishes ATPase activity and results in protein misfolding and proteasomal degradation. No effect on interaction with TMEM30A.
In CAMRQ4; unknown pathological significance; abolishes ATPase activity. No effect on interaction with TMEM30A.
In CAMRQ4; unknown pathological significance; results in protein misfolding and proteasomal degradation.
No effect on flippase activity toward phosphatidylserine. Like the wild type, it is unable to translocate phosphatidylcholine.
Reduced flippase activity toward phosphatidylserine. Like the wild type, it is unable to translocate phosphatidylcholine.
No effect on DYNLL1-binding; when associated with G-436.
No effect on DYNLL1-binding; when associated with G-448.
Interleukin-1 receptor-associated kinase 1-binding protein 1
Decrease in nuclear export; when associated with A-242 and A-246.
Decrease in nuclear export; when associated with A-242 and A-248.
Decrease in nuclear export; when associated with A-246 and A-248.
Decrease in nuclear export; when associated with A-69, A-71 and A-74.
Decrease in nuclear export; when associated with A-69, A-71 and A-76.
Decrease in nuclear export; when associated with A-69, A-74 and A-76.
Decrease in nuclear export; when associated with A-71, A-74 and A-76.
Decrease in phosphorylation, significant decrease in transcriptional repressor activity and reduced interaction with PP1CA, PP1CB and PP1CG. Significant decrease in phosphorylation and transcriptional repressor activity; when associated with A-422.
Disrupts dimerization but does not affect DNA-binding; when associated with Q-348. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and P-372.
Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with Q-348 and T-370.
Forkhead box protein P3, C-terminally processed
In IPEX; mild phenotype; no loss of protein expression.
In IPEX; mild phenotype; no loss of protein expression; impairs its ability to confer inhibitory function to regulatory T-cells; no loss of DNA-binding when associated with A-373.
In IPEX; requires 2 nucleotide substitutions; no loss of protein expression; disrupts dimerization; impairs its ability to confer inhibitory function to regulatory T-cells; no loss of DNA-binding when associated with H-347.
In IPEX; significantly reduces dimerization.
No loss of DNA-binding. Disrupts dimerization but does not affect DNA-binding; when associated with T-370. Disrupts dimerization, does not affect DNA-binding, causes dysregulated expression of a subset of FOXP3 target genes and impairs its ability to confer inhibitory function to regulatory T-cells; when associated with T-370 and P-372.
Significant decrease in phosphorylation and transcriptional repressor activity; when associated with A-418.
Slight increase in transcriptional repressor activity.
(Microbial infection) O-linked (Glc) threonine; by P.sordellii toxin TcsL
Abolished monoglucosylation by P.sordellii toxin TcsL.
Converts geranyl-geranylation to farnesylation. No effect on membrane localization. Fails to deflect GGTI-induced apoptosis of adherent cell cultures, but rescues anchorage-independent cell proliferation.
Decreased localization to mitochondrion. Loss of function in mitochondrial fission.
Impaired cytokinesis, as shown by increased number of binucleate cells. Impaired cytokinesis; when associated with L-72.
Impaired cytokinesis, as shown by increased number of binucleate cells. Impaired cytokinesis; when associated with N-49 or 1-M--S-11. No effect on cytokinesis; when associated with E-49.
Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on cytokinesis; when associated with V-23. Decreased interaction with EXOC2 and EXOC8; when associated with V-23.
Impaired cytokinesis, as shown by increased number of binucleate cells. No effect on interaction with EXOC2 and EXOC8. No effect on cytokinesis; when associated with R-38 or W-48. Decreased interaction with EXOC2 and EXOC8; when associated with R-38 or W-48.
In HINCONS; decreased GTPase activity; decreased RALA effector binding.
In HINCONS; decreased GTPase activity; increased RALA effector binding.
In HINCONS; unknown pathological significance.
Increased localization to mitochondrion.
No effect on cytokinesis. Impaired cytokinesis, as shown by increased number of binucleate cells; when associated with L-72.
No effect on cytokinesis; when associated with L-72.
Strongly reduces interaction with EXOC8.
Voltage-dependent L-type calcium channel subunit beta-1
In RHDA1; the mutant does not localize at the cell membrane.
In RHDA1; unknown pathological significance.
ADP-ribosylation factor-related protein 1
Pulmonary surfactant-associated protein B
Pleckstrin homology domain-containing family G member 3
Leucine-rich repeat-containing protein 43
(Microbial infection) N-beta-linked (GlcNAc) arginine
Abolished GlcNAcylation by E.coli NleB1.
In FPF; unknown pathological significance.
Tumor necrosis factor receptor superfamily member 1A, membrane form
Trafficking protein particle complex subunit 6A
PiggyBac transposable element-derived protein 2
Associated with susceptibility to SLE; associated with resistance to malaria; found at an increased frequency in African and Asian populations from areas where malaria is endemic; enhances phagocytosis of Plasmodium falciparum-infected erythrocytes in vitro.
Low affinity immunoglobulin gamma Fc region receptor II-b
Abolishes phosphorylation by MARK2 and induces defects in the reestablishment of junctional complexes.
Abolishes the interaction with RAB11A and the vesicular localization.
Abolishes the interaction with REPS1 and AP2A1. Modifies its subcellular location and the endocytosis activity. Enhances homooligomerization.
No effect on the interaction with RAB11A. Abolishes the vesicular localization.
Severe reduction of the interaction with REPS1 and AP2A1. No effects on its subcellular location. Modifies the endocytosis activity.
In MYOFTA; no protein detected by western blot in patient muscle.
Myosin light chain 1/3, skeletal muscle isoform
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7 and isoform 8.
In isoform 3, isoform 4, isoform 6 and isoform 8.
Does not significantly impair 25-hydroxycholesterol binding.
Loss of increased cholesterol and decreased phosphatidylinositide accumulation at the cell membrane.
Loss of the ability to promote cholesterol accumulation at the cell membrane. No effect on phosphatidylinositide levels at the cell membrane.
Mildly decreased 25-hydroxycholesterol binding.
No effect on phosphatidylinositide binding, but decreased cholesterol binding, plus decreased cholesterol and phosphatidylinositide transport.
No effect on phosphatidylinositide binding, but impaired tetramerization and decreased cholesterol binding, plus decreased cholesterol and phosphatidylinositide transport.
Oxysterol-binding protein-related protein 2
Reduces 25-hydroxycholesterol binding. Loss of 22(R)-hydroxycholesterol binding.
DNA replication complex GINS protein PSF2
This is the measured mass for the GINS complex.
Calcium-activated chloride channel regulator 1
Zinc-regulated GTPase metalloprotein activator 1A
9-fold reduction in binding affinity for Link domain of TNFAIP6.
Cytoplasmic polyadenylation element-binding protein 4
Abolishes stimulation of RENT1 dephosphorylation.
Nonsense-mediated mRNA decay factor SMG5
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform
Gypsy retrotransposon integrase-like protein 1
In BBS3; abrogates the GTP-binding ability without affecting GDP-binding/dissociating properties; increased proteasomal degradation.
In BBS3; abrogates the GTP-binding ability; increased proteasomal degradation.
In BBS3; locked in a GDP-bound state that differs from its wild-type counterpart which is mainly GTP-bound; increased proteasomal degradation.
Mitochondrial import receptor subunit TOM40 homolog
Adaptin ear-binding coat-associated protein 2
Histone-lysine N-methyltransferase SETDB1
In HCVAD; decreased beta-carotene 15,15'-monooxygenase activity; 90% decrease compared to wild-type; decreased catalytic efficiency; no effect on affinity for all-trans-beta-carotene.
Sister chromatid cohesion protein PDS5 homolog B
Decreased activity; when associated with L-66.
Decreased activity; when associated with T-68.
Impaired ATM mediated phosphorylation, but normal interaction with HIPK2 and HIPK2 subsequent proteasomal degradation.
In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-226.
In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-161; A-162 and A-237.
In A; does not impair its ability to degrade PML while it abolishes its ability to interact with CACYBP and degrade CTNNB1; when associated with A-226 and A-237.
In B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-253.
In B; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-265.
In BURHAS; loss of function in Wnt signaling pathway.
In C; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-233.
In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-214 and A-215.
In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-124; A-231 and A-232.
In D; does not impair its ability to interact with CACYBP and degrade CTNNB1 and PML; when associated with A-214; A-215; A-231 and A-232.
In E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-142.
In E; does not impair its ability to interact with CACYBP and degrade CTNNB1; when associated with A-151.
Loss of function; when associated with A-55 and A-59.
Loss of function; when associated with A-55 and S-72.
Loss of function; when associated with A-59 and S-72.
Loss of function; when associated with S-44.
Loss of function; when associated with Y-59.
Reduced interaction with HIPK2 and HIPK2 subsequent proteasomal degradation.
Abrogates the interaction with BRCA1; decreases double-stranded DNA break-initiated homologous recombination; reduces PALB2 and RAD51 localization to ionizing radiation-induced foci; may weaken homooligomerization.
Decreases double-stranded DNA break-initiated homologous recombination.
In BC; abrogates the interaction with BRCA1; abrogates double-stranded DNA break-initiated homologous recombination; abrogates PALB2 and RAD51 localization to ionizing radiation-induced foci; may weaken homooligomerization.
Loss of interaction with BRCA1 but no effect on interaction with BRCA2.
May be associated with breast cancer susceptibility.
May be associated with breast cancer susceptibility; reduces interaction with BRCA2, RAD51 and XRCC3; decreases double-stranded DNA break-initiated homologous recombination; increases sensitivity to IR.
May be associated with breast cancer susceptibility; reduces interaction with BRCA2, RAD51C, RAD51 and XRCC3; decreases double-stranded DNA break-initiated homologous recombination; increases sensitivity to IR.
Unstable and promotes protein degradation; reduces interaction with RAD51C and RAD51.
Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase
Abolishes phosphorylation and apoptotic activity.
No effect on phosphorylation or apoptotic activity.
Acidic fibroblast growth factor intracellular-binding protein
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4
Induces a major structural rearrangement accompanied by domain-swapping dimerization and changes in substrate-specificity.
No effect on PPP2R1A-binding. Impaired ability to act as a host factor for picornaviruses.
Disintegrin and metalloproteinase domain-containing protein 29
In a cutaneous metastatic melanoma sample; somatic mutation.
In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV.
Coiled-coil domain-containing protein 157
DNA polymerase subunit gamma-2, mitochondrial
In MTDPS16; decreased function in mitochondrial DNA replication; decreased protein stability; no effect on DNA binding.
In MTDPS16B; decreased DNA polymerase processivity factor activity; results in decreased stability; affects the secondary structure as shown by circular dichroism spectroscopy.
In PEOA4; affects stimulation of the catalytic subunit.
Abolishes ability to mediate depalmitoylation of ZDHHC6.
Coiled-coil domain-containing protein 115
Coordinator of PRMT5 and differentiation stimulator
In CMH10; decrease calcium binding affinity.
In CMH10; impairs calcium binding; bind calcium upon phosphorylation.
In CMH10; some patients present with mid-left ventricular chamber thickening; significantly decrease calcium binding affinity; loss of phosphorylation.
In CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity.
In CMH10; with mid-left ventricular chamber thickening; decrease calcium binding affinity; large increase in its calcium binding affinity upon phosphorylation.
Myosin regulatory light chain 2, ventricular/cardiac muscle isoform
Gain of pH-sensitivity of E1S transport.
Solute carrier organic anion transporter family member 1C1
Probable tRNA (uracil-O(2)-)-methyltransferase
In CILD45; reduced protein abundance; changed axonemal dynein complex assembly.
In CILD45; reduced protein abundance; changed axonemal dynein complex assembly; loss of sperm axoneme assembly.
Ganglioside-induced differentiation-associated protein 1-like 1
Reduces binding to T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence.
Abolishes interaction with ELP1 and ELP3.
In MRT58; unknown pathological significance.
No effect on interaction with ELP1 or ELP3; when associated with A-634, A-636 and A-670.
No effect on interaction with ELP1 or ELP3; when associated with A-634, A-636 and A-689.
No effect on interaction with ELP1 or ELP3; when associated with A-634, A-670 and A-689.
No effect on interaction with ELP1 or ELP3; when associated with A-636, A-670 and A-689.
In HH12; uncertain pathological significance; the patient also carries mutations in PROKR2 and FGFR1.
DRY motif; important for ligand-induced conformation changes
Increased ability of hallucinogens to desensitize the receptor.
Loss of interaction with PATJ, CASK, APBA1, DLG1 and DLG4.
NPxxY motif; important for ligand-induced conformation changes and signaling
No effect on interaction with PATJ. Acquires the binding properties of HTR2C; when associated with S-465.
No effect on interaction with PATJ. Acquires the binding properties of HTR2C; when associated with S-470.
Reduced receptor desensitization by nonhallucinogenic agonists.
Strongly increases dissociation of bound lysergic acid diethylamine, without affecting binding affinity. Reduces signaling via arrestins, but has no effect on signaling via the phosphatidylinositol-calcium second messenger system.
Greatly reduced binding to AKT1, AKT2 and AKT3. Abolishes nuclear transport of AKT1.
Greatly reduced binding to AKT2. Abolishes nuclear transport of AKT1.
Unable to homodimerize but has no effect on interaction with AKT1, AKT2 or AKT3.
Gamma-aminobutyric acid receptor subunit rho-1
Cyclin-dependent kinase 2-associated protein 2
Loss of function. Probably due to defects in formation of the active site and binding of coenzyme.
Found in a family with atypical autism and severe epilepsy; unknown pathological significance.
In CYSRD; may impair splicing; hypomorphic mutation.
Adenosine 3'-phospho 5'-phosphosulfate transporter 1
Ribonucleases P/MRP protein subunit POP1
POZ-, AT hook-, and zinc finger-containing protein 1
Complete loss of type I receptor binding.
TOG array regulator of axonemal microtubules protein 2
Abrogates kinase activity and TFIIH-dependent transcriptional repression.
In IDDHBA; decreased protein kinase activity.
In IDDHBA; unknown pathological significance.
Neuronal vesicle trafficking-associated protein 1
Associated with susceptibility to IDDM19.
In AGS7; enhances IFNB1 promoter activation; loss of ligand-induced responsiveness.
In AGS7; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; enhances IFNB1 promoter activation; no loss of ATP hydrolysis.
In AGS7; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis.
In IMD95; does not bind the double-stranded RNA analog poly(I:C); loss of IFNB1 and NFKB promoter activation after stimulation with poly(I:C), when tested in a luciferase reporter assay.
In IMD95; no protein detected by Western blot in homozygous patient cells.
In SGMRT1; gain-of-function mutation resulting in enhanced INFB1 induction.
Inhibits multimerization after polyI:C stimulation.
Interferon-induced helicase C domain-containing protein 1
Loss of ISGylation, loss of oligomerization, strongly reduced signaling activity and IFNB induction, loss of virus replication restriction, no effect on phosphorylation or RNA-binding; when associated with A-23.
Loss of ISGylation, loss of oligomerization, strongly reduced signaling activity and IFNB induction, loss of virus replication restriction, no effect on phosphorylation or RNA-binding; when associated with A-43.
Loss of dsRNA-induced ATPase activity. Loss of MDA-5 signaling pathway.
Loss of dsRNA-induced ATPase activity. No effect on MDA-5 signaling pathway.
Loss of dsRNA-induced ATPase activity. No effect on RNA binding. Changed MDA-5 signaling pathway.
Loss of signaling activity and IFNB induction. Reduced ISGylation. Loss of virus replication restriction.
No acceleration of DNA degradation, no binding to ATP, and no helicase activity.
No cleavage and no acceleration of DNA degradation.
No effect on ISGylation or signaling activity and IFNB induction.
Promotes multimerization after polyI:C stimulation; greatly enhances signaling.
N-terminal EF-hand calcium-binding protein 2
Ankyrin repeat and MYND domain-containing protein 2
Inositol 1,4,5-triphosphate receptor associated 1
Found in a patient with Leigh syndrome; unknown pathological significance.
In CAGSSS; unknown pathological significance.
In DEE49; unknown pathological significance.
Loss of enzymatic activity. Increases the steady-state level of CCND1.
Loss of enzymatic activity. Increases the steady-state level of MDM2 and MDM4 that leads to attenuation of MDM2-mediated degradation of p53/TP53 and MDM4. Increases the level of p53/TP53 and MDM4 ubiquitin conjugates.
Glutathione S-transferase C-terminal domain-containing protein
In XLID19; kinase activity is decreased but not abolished.
Phosphoserine; by autocatalysis and MAPKAPK2
In MCOP3; does not affect nuclear localization; reduces DNA binding activity.
In MCOP3; unknown pathological significance.
Affects chain elongation resulting in shorter products.
Dehydrodolichyl diphosphate synthase complex subunit DHDDS
Delays cell growth; when associated with A-306 and A-313.
Delays cell growth; when associated with A-306 and A-317.
Delays cell growth; when associated with A-313 and A-317.
In DEDSM; also found in a patient with progressive myoclonus epilepsy and developmental delay; unknown pathological significance.
In DEDSM; unknown pathological significance.
In RP59; 5-fold reduction in catalytic activity and reduced affinity for FPP but not for IPP..
Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-12 and A-15.
Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-12 and A-19.
Markedly decreases phosphatidylinositol-mediated activation of cis-prenyltransferase activity resulting in products with longer chain length; when associated with A-15 and A-19.
In PEOB2; has partial residual endonuclease activity.
Transcription termination factor 2, mitochondrial
Cytosolic iron-sulfur assembly component 3
Decreased 3',5'-cyclic-AMP phosphodiesterase activity. Decreased 3',5'-cyclic-GMP phosphodiesterase activity.
Decreased 3',5'-cyclic-AMP phosphodiesterase activity. Increased 3',5'-cyclic-GMP phosphodiesterase activity.
Decreased 3',5'-cyclic-AMP phosphodiesterase activity. Loss of 3',5'-cyclic-GMP phosphodiesterase activity.
Decreased 3',5'-cyclic-AMP phosphodiesterase activity. No effect on 3',5'-cyclic-GMP phosphodiesterase activity.
In IDDPADS; unknown pathological significance.
In IDDPADS; unknown pathological significance; loss of 3',5'-cyclic-AMP phosphodiesterase activity; loss of 3',5'-cyclic-GMP phosphodiesterase activity.
Loss of 3',5'-cyclic-AMP phosphodiesterase activity. Decreased 3',5'-cyclic-GMP phosphodiesterase activity.
Loss of 3',5'-cyclic-AMP phosphodiesterase activity. Loss of 3',5'-cyclic-GMP phosphodiesterase activity.
No effect on 3',5'-cyclic-AMP phosphodiesterase activity. Decreased 3',5'-cyclic-GMP phosphodiesterase activity.
cGMP-dependent 3',5'-cyclic phosphodiesterase
Ankyrin repeat domain-containing protein 45
In PPSH; also in individuals with micropenis; increased affinity for testosterone; increased affinity for NADPH; decreased Vmax.
Increased affinity for testosterone; increased affinity for NADPH; decreased Vmax.
Increased affinity for testosterone; increased affinity for NADPH; decreased Vmax; no effect on affinity for testosterone when associated with L-89; increased affinity for NADPH when associated with L-89; decreased Vmax when associated with L-89.
Increased affinity for testosterone; no effect on affinity for NADPH; increased Vmax; no effect on affinity for testosterone when associated with L-89; no effect on affinity for NADPH when associated with L-89; increased Vmax when associated with L-89.
No effect on affinity for testosterone; increased affinity for NADPH; decreased Vmax.
No effect on affinity for testosterone; increased affinity for NADPH; decreased Vmax; decreased affinity for testosterone when associated with L-89; increased affinity for NADPH when associated with L-89; decreased Vmax when associated with L-89.
No effect on affinity for testosterone; increased affinity for NADPH; increased Vmax.
No effect on affinity for testosterone; no effect on affinity for NADPH; decreased Vmax; no effect on affinity for testosterone when associated with T-49; no effect on affinity for NADPH when associated with T-49; increased Vmax when associated with T-49; decreased affinity for testosterone when associated with M-187; increased affinity for NADPH when associated with M-187; decreased Vmax when associated with M-187; no effect on affinity for testosterone when associated with L-234; increased affinity for NADPH when associated with L-234; decreased Vmax when associated with L-234.
No effect on affinity for testosterone; no effect on affinity for NADPH; no effect on Vmax.
Abolished isopeptidase activity and reduced transamidase activity.
Abolished isopeptidase and transamidase activities.
Abolished protein-glutamine gamma-glutamyltransferase activity without affecting alpha-1 adrenergic receptor signaling. Abolished isopeptidase activity.
Abolished protein-glutamine gamma-glutamyltransferase activity without affecting cytotoxic activity.
Abolishes GTP-binding and transglutaminase activities. Does not have cytotoxic activity when overexpressed.
Displays lower Ca(2+)-binding affinity and reduced transglutaminase activity.
Does not affect the protein-glutamine deamidase activity.
Dominant negative mutant. Abolishes WDR54 cross-linking.
Impaired Ca(2+)-binding leading to reduced transglutaminase activity.
Impaired substrate recognition for the protein-glutamine deamidase activity.
In TG2-I; strongly reduced transamidase activity without affecting the isopeptidase activity.
In TG2-T; strongly reduced isopeptidase activity without affecting the transamidase activity.
In patients with early-onset diabetes type 2; unknown pathological significance.
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
No effect on isopeptidase and transamidase activities.
Protein-glutamine gamma-glutamyltransferase 2
Reduced isopeptidase and transamidase activities.
Substitution with F13A1 sequence. Abolished interaction with phospholipase C and ability to promote alpha-1 adrenergic receptor signaling.
2.5-fold increase in affinity for indolepropinoic acyl-adenylate and cytosine; 2-fold decrease in hypoxanthine affinity; nearly no change in affinity for adenine, guanine and uracil.
Abolishes adenosine 5'-monophosphoramidase activity.
Probable methyltransferase-like protein 24
In IMD63; decreased protein abundance; changed IL-2 and IL-15 signaling pathways; plasma levels of both IL2 and IL15 were increased; associated with increased amounts of phosphorylated STAT5A.
Partial loss of interaction with SHB; when associated with F-418.
Partial loss of interaction with SHB; when associated with F-536.
Mitochondrial amidoxime-reducing component 1
No effect on binding of the molybdenum cofactor; no significant effect on catalytic efficiency toward benzamidoxime; no significant effect on affinity for benzamidoxime.
Associated with susceptibility to ischemic stroke; increases autophosphorylation and kinase activity.
In a aLL TEL/AML1+ sample; somatic mutation.
Abolishes interaction with CHMP4B; when associated with D-202.
In NEDBASS; unknown pathological significance.
In NEDBASS; when associated in cis with H-1017; unknown pathological significance.
In NEDBASS; when associated in cis with R-583; unknown pathological significance.
Nearly abolishes interaction with CHMP4B. Abolishes interaction with CHMP4B; when associated with D-206.
Tyrosine-protein phosphatase non-receptor type 23
Found in patients with propionic acidemia; does not affect either heteromeric or homomeric assembly; decreased thermostability affecting holoenzyme oligomerization; no effect on propionyl-CoA carboxylase activity.
In PA-2; affects heteromeric and homomeric assembly.
In PA-2; does not affect either heteromeric or homomeric assembly.
In PA-2; no effect on affinity for propionyl-CoA; decreased reaction kinetics for the propionyl-CoA carboxylase activity; decreased thermostability affecting holoenzyme oligomerization.
Propionyl-CoA carboxylase beta chain, mitochondrial
Acts as a disease modifier in patients with aminoglycoside-induced deafness and a mutation in mitochondrial 12S rRNA; affects tRNA processing by decreasing thiolation and increasing aminoacylation of tRNAs; the mutant has lower thermal stability than wild-type; does not affect import in the mitochondria.
Mitochondrial tRNA-specific 2-thiouridylase 1
Abolishes interaction with VCP and E3 ligase activity toward mutant SOD1; when associated with S-132.
Abolishes interaction with VCP and E3 ligase activity toward mutant SOD1; when associated with S-135.
In THC5; abrogates DNA binding; alters subcellular location; decreases transcriptional repression in a dominant-negative fashion.
In one individual with AML; somatic mutation; unable to repress transcription.
Decreased ability to interact with and package the SNARE SEC22B cargo into COPII vesicles. Has no effect on other cargos packaging.
In CDG2W; affects the endoplasmic reticulum subcellular location, relocalizing the protein either to the Golgi apparatus, or to a distinct, non-Golgi compartment, possibly endoplasmic reticulum exit sites; when transfected into HepG2 cells, significantly changes the protein glycosylation pattern, such as that of transferrin; does not affect glucose-6-phosphate transport activity.
In GSD1B; inactive glucose-6-phosphate transport.
Glycine N-acyltransferase-like protein 1
Platelet-activating factor acetylhydrolase IB subunit alpha2
In isoform 10, isoform 13 and isoform 14.
In isoform 12, isoform 15 and isoform 18.
In isoform 6, isoform 16 and isoform 17.
In isoform 8, isoform 13 and isoform 14.
Kringle-containing protein marking the eye and the nose
Dual specificity mitogen-activated protein kinase kinase 5
Abolishes interaction with all sialic acid-containing glycans.
Inhibits binding to the 9-O-acetylated sialic acid derivatives.
Lactosylceramide alpha-2,3-sialyltransferase
Receptor-type tyrosine-protein phosphatase kappa
Abolishes interaction with CSK and impairs inhibition of NF-AT activation.
No effect on interaction with PTPN11 or GRB2.
Reduces interaction with GRB2. Abolishes interaction with GRB2; when associated with F-188.
Reduces interaction with GRB2. Abolishes interaction with GRB2; when associated with F-90.
Reduces interaction with PTPN11, no effect on inhibition of NF-AT activation.
Signaling threshold-regulating transmembrane adapter 1
Benign variant; no effect on PYCARD/ASC inflammasome formation.
Does not form MEFV- and PSTPIP1-containing perinuclear specks.
In PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B and IL18 production; decreased interaction with 14-3-3 proteins; no effect on interaction with PSTPIP1.
In PAAND; results in constitutive inflammasome activation; increased PYCARD/ASC specks formation; increased caspase-1 activation and IL1B production; loss of S-242 phosphorylation; loss of interaction with 14-3-3 proteins.
In arFMF and adFMF; associated with Q-148 in some patients; no effect on PYCARD/ASC inflammasome formation; no effect on interaction with 14-3-3 proteins.
In arFMF and adFMF; likely benign variant; associated with S-369 and Q-408 in cis; associated with I-694 in some patients.
In arFMF and adFMF; reduced CASP1 interaction; decreased interaction with ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation; when associated with V-694 (PubMed:26347139); no effect on PYCARD/ASC inflammasome formation; no effect on interaction with 14-3-3 proteins.
In arFMF and adFMF; very common mutation particularly in North African Jews; can be associated with amyloidosis development; reduced interaction with CASP1 and with ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation (PubMed:16785446) (PubMed:26347139); effect on autophagic NLRP3 degradation is increased; when associated with I-680; no effect on interaction with CASP1, CASP5, NLRP1, NLRP2 or NLRP3 (PubMed:17431422).
In arFMF; associated with Q-148 and S-369 in cis.
In arFMF; common mutation; in Iraqi and Ashkenazi Jews, Druze, Armenians; reduced interaction with CASP1 and ULK1 and diminished NLRP3 degradation after induction of autophagy by starvation; when associated with I-680 and V-694; no effect on CASP1 activation; no effect on interaction with 14-3-3 proteins.
In arFMF; reduced penetrance among Ashkenazi Jews.
In arFMF; uncertain pathological significance.
In arFMF; unknown pathological significance.
In arFMF; unknown pathological significance; associated with Q-148 and Q-408 in cis.
In arFMF; unknown pathological significance; no effect on PYCARD/ASC inflammasome formation.
In one patient with familial Mediterranean fever.
Increased PYCARD/ASC specks formation. Decreased interaction with 14-3-3 proteins.
Loss of interaction with 14-3-3 proteins.
No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 397-I--H-404 and 470-Y--G-488.
No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 397-I--H-404 and 523-S--D-530.
No effect on GABARAP-binding. Loss of GABARAP-binding; when associated with 470-Y--G-488 and 523-S--D-530.
No effect on PYCARD/ASC specks formation. Increased interaction with 14-3-3 proteins.
No effect on PYCARD/ASC specks formation. No effect on interaction with 14-3-3 proteins.
Probable disease-associated variant found in an autosomal dominant autoinflammatory disease with some similarities to familial Mediterranean fever.
N-acetylmethionine; in Sorting nexin-6, N-terminally processed
Reduces interaction with SNX1. Abolishes location at endosome membranes.
Affects autocatalytic cleavage and production of Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment.
Affects autocatalytic cleavage and production of Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment.
Atrial natriuretic peptide-converting enzyme
Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment
Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment
Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment
Atrial natriuretic peptide-converting enzyme, N-terminal propeptide
Atrial natriuretic peptide-converting enzyme, activated protease fragment
Impairs cell membrane targeting; when associated with A-26.
Impairs cell membrane targeting; when associated with A-30.
Interchain (between N-terminal propeptide and activated protease fragment chains)
Abolishes cleavage but does not affect cell membrane localization or signaling activity.
Abolishes heparin-binding; when associated with A-28 and A-33.
Abolishes heparin-binding; when associated with A-29 and A-33.
In BFPP; abolishes autoproteolytic cleavage; reduces cell surface localization.
In BFPP; abolishes interaction with COL3A1.
In BFPP; abolishes interaction with COL3A1; reduces cell surface localization.
In BFPP; reduces cell surface localization.
In BFPP; unclear effects on cell surface localization; blocks downstream RhoA activation.
Reduces heparin-binding. Abolishes heparin-binding; when associated with A-28 and A-29.
Abolishes enzymatic activity. Increased interaction with diubiquitin.
Decreased interaction with diubiquitin. No accumulation of free diubiquitin. Decreased levels of polyubiquitinated lysozyme.
Ubiquitin carboxyl-terminal hydrolase isozyme L3
Abolishes splicing regulation activity and interaction with RNPS1 and ACIN1; when associated with A-118.
Abolishes splicing regulation activity and interaction with RNPS1 and ACIN1; when associated with A-121.
Histone deacetylase complex subunit SAP18
No effect on splicing regulation activity.
Blocks the inhibition of transcription by RPS6KA5/MSK1.
Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with N-767 and Y-775.
Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with N-767 and Y-853.
Changes substrate selectivity from cGMP-specific to dual cAMP and cGMP binding and hydrolysis; when associated with Y-775 and Y-853.
cGMP-specific 3',5'-cyclic phosphodiesterase
In CTRCT20; unknown pathological significance.
Leucine-rich repeat-containing protein 10
Decreases the single-channel open probability (Po) without altering its conductance.
Found in a patient with hypokalemic periodic paralysis without hyperthyroidism; reduces potassium inward and outward currents density.
Found in a patient with sporadic periodic paralysis; unknown pathological significance; abolishes potassium inward and outward currents density; reduces cell surface abundance.
Found in a patient with sporadic periodic paralysis; unknown pathological significance; decreases potassium inward and outward currents density; reduces cell surface abundance; reduces conductance; dominant negative mutation.
In TTPP2; abolishes potassium inward and outward currents density.
In TTPP2; hypermorphic; longer time required for half-maximal current degradation.
In TTPP2; reduces potassium inward and outward currents density.
In TTPP2; small decrease in current density.
In TTPP2; unknown pathological significance; decreases potassium inward and outward currents density; reduces cell surface abundance; reduces open propability; dominant negative mutation.
Abolishes binding to membranes enriched in phosphatidylinositol 3-phosphate.
Abolishes binding to phosphatidylinositol 3-phosphate.
28S ribosomal protein S29, mitochondrial
Abolishes interaction with CHUK; when associated with A-11; A-12 and A-230.
Abolishes interaction with CHUK; when associated with A-11; A-12 and A-231.
Abolishes interaction with CHUK; when associated with A-11; A-230 and A-231.
Abolishes interaction with CHUK; when associated with A-12; A-230 and A-231.
Inhibits internalization of CXCR4; no effect on interaction with CXCR4.
Reduces interaction with CHUK; when associated with A-360.
Reduces interaction with CHUK; when associated with A-382.
Isoamyl acetate-hydrolyzing esterase 1 homolog
BAG family molecular chaperone regulator 2
Choriogonadotropin subunit beta variant 2
2-oxoglutarate and iron-dependent oxygenase domain-containing protein 2
Peptidyl-tRNA hydrolase ICT1, mitochondrial
Strongly impairs peptide release activity.
Zinc finger SWIM domain-containing protein 8
Loss of localization of CAMSAP2 stretches to the Golgi apparatus; when associated with A-226.
Loss of localization of CAMSAP2 stretches to the Golgi apparatus; when associated with A-234.
Microtubule-associated protein RP/EB family member 3
CMP-N-acetylneuraminate-beta-galactosamide-alpha-2,3-sialyltransferase 4
Ankyrin repeat domain-containing protein 61
Strongly reduced enzyme activity. No effect on trimerization and on heme binding.
Coiled-coil domain-containing protein 69
Associated with an increased risk for intervertebral disk disease.
In NEDMCMS; changed alternative splicing; decreased protein abundance; homozygous patient cells show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity.
In NEDMCMS; increased homodimerization; even in absence of oxidative stress.
In NEDMCMS; unknown pathological significance.
Increased homodimerization even in absence of oxidative stress.
Thioredoxin-related transmembrane protein 2
Fails to form damage-dependent nuclear foci or interact with H2AX.
RNA-binding motif, single-stranded-interacting protein 2
Regenerating islet-derived protein 3-gamma 15 kDa form
Regenerating islet-derived protein 3-gamma 16.5 kDa form
Allele DPB1*41:01 and allele DPB1*83:01.
HLA class II histocompatibility antigen, DP beta 1 chain
In allele DPB1*01:01, allele DPB1*01:02, allele DPB1*09:02, allele DPB1*11:01, allele DPB1*13:01, allele DPB1*15:01, allele DPB1*20:02, allele DPB1*21:02, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*39:01, allele DPB1*40:01, allele DPB1*49:01, allele DPB1*53:01, allele DPB1*65:01, allele DPB1*74:01, allele DPB1*85:01, allele DPB1*89:01 and allele DPB1*96:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*03:02, allele DPB1*04:03, allele DPB1*05:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*08:01, allele DPB1*08:02, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:01, allele DPB1*11:01, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*13:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:01, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*19:01, allele DPB1*21:01, allele DPB1*21:01, allele DPB1*21:02, allele DPB1*21:02, allele DPB1*20:01, allele DPB1*22:01, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*31:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*38:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*56:01, allele DPB1*57:01, allele DPB1*58:01, allele DPB1*63:01, allele DPB1*65:01, allele DPB1*67:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*84:01, allele DPB1*85:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*89:01, allele DPB1*90:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01, allele DPB1*97:01 and allele DPB1*98:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*03:02, allele DPB1*04:03, allele DPB1*05:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*08:01, allele DPB1*08:02, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:01, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:01, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*19:01, allele DPB1*21:01, allele DPB1*21:02, allele DPB1*20:01, allele DPB1*22:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*31:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*38:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*56:01, allele DPB1*57:01, allele DPB1*58:01, allele DPB1*63:01, allele DPB1*65:01, allele DPB1*67:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*84:01, allele DPB1*85:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*89:01, allele DPB1*90:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01, allele DPB1*97:01 and allele DPB1*98:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*03:02, allele DPB1*04:03, allele DPB1*05:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*08:01, allele DPB1*08:02, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:01, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:01, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*19:01, allele DPB1*21:01, allele DPB1*21:02, allele DPB1*20:01, allele DPB1*22:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*31:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*38:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*56:01, allele DPB1*58:01, allele DPB1*63:01, allele DPB1*65:01, allele DPB1*67:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*84:01, allele DPB1*85:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*89:01, allele DPB1*90:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01, allele DPB1*97:01 and allele DPB1*98:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*05:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*13:01, allele DPB1*14:01, allele DPB1*15:01, allele DPB1*18:01, allele DPB1*19:01, allele DPB1*20:01, allele DPB1*26:01, allele DPB1*45:01 and allele DPB1*85:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:01, allele DPB1*11:02, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*15:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*18:01, allele DPB1*20:02, allele DPB1*21:01, allele DPB1*21:02, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*56:01, allele DPB1*58:01, allele DPB1*66:01, allele DPB1*67:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*74:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*85:01, allele DPB1*86:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*89:01, allele DPB1*90:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01 and allele DPB1*98:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*09:02, allele DPB1*11:01, allele DPB1*11:02, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*14:02, allele DPB1*15:01, allele DPB1*17:02, allele DPB1*18:01, allele DPB1*20:02, allele DPB1*21:01, allele DPB1*21:02, allele DPB1*20:01, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*44:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*56:01, allele DPB1*69:01, allele DPB1*74:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*85:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*89:01, allele DPB1*90:01, allele DPB1*92:01 and allele DPB1*93:01.
In allele DPB1*01:01, allele DPB1*03:01, allele DPB1*05:02, allele DPB1*08:01, allele DPB1*09:01, allele DPB1*10:01, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*17:02, allele DPB1*21:02, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:01, allele DPB1*29:01, allele DPB1*35:01, allele DPB1*37:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*56:01, allele DPB1*57:01, allele DPB1*65:01, allele DPB1*67:01, allele DPB1*68:01, allele DPB1*70:01, allele DPB1*73:01, allele DPB1*75:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*84:01, allele DPB1*88:01, allele DPB1*90:01 and allele DPB1*92:01.
In allele DPB1*01:02, allele DPB1*02:01, allele DPB1*02:02, allele DPB1*02:03, allele DPB1*03:01, allele DPB1*04:02, allele DPB1*04:03, allele DPB1*05:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*06:02, allele DPB1*08:01, allele DPB1*08:02, allele DPB1*09:01, allele DPB1*10:01, allele DPB1*10:02, allele DPB1*11:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*15:02, allele DPB1*16:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*18:01, allele DPB1*18:02, allele DPB1*19:01, allele DPB1*19:02, allele DPB1*21:01, allele DPB1*20:01, allele DPB1*22:01, allele DPB1*22:02, allele DPB1*23:01, allele DPB1*25:01, allele DPB1*26:02, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*32:01, allele DPB1*34:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*38:01, allele DPB1*41:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*46:01, allele DPB1*47:01, allele DPB1*48:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*57:01, allele DPB1*58:01, allele DPB1*59:01, allele DPB1*60:01, allele DPB1*62:01, allele DPB1*63:01, allele DPB1*67:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*71:01, allele DPB1*73:01, allele DPB1*75:01, allele DPB1*77:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*80:01, allele DPB1*82:01, allele DPB1*83:01, allele DPB1*84:01, allele DPB1*86:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*91:01, allele DPB1*93:01, allele DPB1*94:01, allele DPB1*95:01, allele DPB1*97:01 and allele DPB1*98:01.
In allele DPB1*01:02, allele DPB1*02:02, allele DPB1*02:03, allele DPB1*05:01, allele DPB1*08:02, allele DPB1*17:02, allele DPB1*19:01, allele DPB1*21:01, allele DPB1*22:01, allele DPB1*24:01, allele DPB1*30:01, allele DPB1*36:01, allele DPB1*38:01, allele DPB1*47:01, allele DPB1*54:01, allele DPB1*84:01 and allele DPB1*97:01.
In allele DPB1*02:01, allele DPB1*02:02, allele DPB1*02:03, allele DPB1*04:03, allele DPB1*06:01, allele DPB1*08:01, allele DPB1*08:02, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:02, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*16:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*18:02, allele DPB1*19:01, allele DPB1*20:02, allele DPB1*21:01, allele DPB1*22:01, allele DPB1*26:02, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*32:01, allele DPB1*33:01, allele DPB1*37:01, allele DPB1*41:01, allele DPB1*44:01, allele DPB1*46:01, allele DPB1*47:01, allele DPB1*48:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*58:01, allele DPB1*71:01, allele DPB1*81:01, allele DPB1*86:01, allele DPB1*88:01, allele DPB1*93:01 and allele DPB1*95:01.
In allele DPB1*02:01, allele DPB1*03:01, allele DPB1*04:02, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*06:02, allele DPB1*08:01, allele DPB1*09:01, allele DPB1*10:01, allele DPB1*10:02, allele DPB1*11:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*18:01, allele DPB1*18:01, allele DPB1*18:02, allele DPB1*19:02, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:02, allele DPB1*28:01, allele DPB1*29:01, allele DPB1*32:01, allele DPB1*35:01, allele DPB1*37:01, allele DPB1*41:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*46:01, allele DPB1*48:01, allele DPB1*49:01, allele DPB1*50:01, allele DPB1*51:01, allele DPB1*53:01, allele DPB1*57:01, allele DPB1*59:01, allele DPB1*60:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*73:01, allele DPB1*75:01, allele DPB1*76:01, allele DPB1*77:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*80:01, allele DPB1*81:01, allele DPB1*82:01, allele DPB1*83:01, allele DPB1*86:01, allele DPB1*88:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01, allele DPB1*94:01 and allele DPB1*98:01.
In allele DPB1*02:01, allele DPB1*03:01, allele DPB1*04:02, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*06:02, allele DPB1*08:01, allele DPB1*09:01, allele DPB1*10:01, allele DPB1*10:02, allele DPB1*11:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*18:01, allele DPB1*18:02, allele DPB1*19:02, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*25:02, allele DPB1*26:02, allele DPB1*28:01, allele DPB1*29:01, allele DPB1*32:01, allele DPB1*35:01, allele DPB1*37:01, allele DPB1*41:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*46:01, allele DPB1*48:01, allele DPB1*49:01, allele DPB1*50:01, allele DPB1*51:01, allele DPB1*53:01, allele DPB1*57:01, allele DPB1*59:01, allele DPB1*60:01, allele DPB1*68:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*73:01, allele DPB1*75:01, allele DPB1*76:01, allele DPB1*77:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*80:01, allele DPB1*81:01, allele DPB1*82:01, allele DPB1*83:01, allele DPB1*84:01, allele DPB1*86:01, allele DPB1*88:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01, allele DPB1*94:01 and allele DPB1*98:01.
In allele DPB1*02:02, allele DPB1*02:03, allele DPB1*05:01, allele DPB1*15:02, allele DPB1*17:02, allele DPB1*19:02, allele DPB1*21:01, allele DPB1*21:01, allele DPB1*22:01, allele DPB1*34:01, allele DPB1*36:01, allele DPB1*38:01, allele DPB1*44:01, allele DPB1*48:01, allele DPB1*58:01, allele DPB1*62:01, allele DPB1*63:01, allele DPB1*95:01 and allele DPB1*97:01.
In allele DPB1*03:01, allele DPB1*03:02, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*10:02, allele DPB1*11:01, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*15:01, allele DPB1*17:02, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*28:01, allele DPB1*29:01, allele DPB1*31:01, allele DPB1*34:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*50:01, allele DPB1*52:01, allele DPB1*56:01, allele DPB1*57:01, allele DPB1*59:01, allele DPB1*67:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*72:01, allele DPB1*73:01, allele DPB1*74:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*87:01, allele DPB1*91:01, allele DPB1*92:01 and allele DPB1*95:01.
In allele DPB1*03:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*09:01, allele DPB1*09:02, allele DPB1*10:01, allele DPB1*11:01, allele DPB1*11:02, allele DPB1*13:01, allele DPB1*13:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*17:02, allele DPB1*20:02, allele DPB1*21:01, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*25:01, allele DPB1*26:01, allele DPB1*27:01, allele DPB1*29:01, allele DPB1*30:01, allele DPB1*35:01, allele DPB1*36:01, allele DPB1*37:01, allele DPB1*44:01, allele DPB1*45:01, allele DPB1*52:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*56:01, allele DPB1*58:01, allele DPB1*66:01, allele DPB1*67:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*74:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*79:01, allele DPB1*85:01, allele DPB1*86:01, allele DPB1*87:01, allele DPB1*88:01, allele DPB1*91:01, allele DPB1*92:01, allele DPB1*93:01 and allele DPB1*98:01; requires 2 nucleotide substitutions.
In allele DPB1*03:01, allele DPB1*05:02, allele DPB1*06:01, allele DPB1*09:01, allele DPB1*10:02, allele DPB1*14:01, allele DPB1*14:02, allele DPB1*17:01, allele DPB1*20:01, allele DPB1*22:02, allele DPB1*29:01, allele DPB1*35:01, allele DPB1*44:01, allele DPB1*46:01, allele DPB1*50:01, allele DPB1*57:01, allele DPB1*69:01, allele DPB1*70:01, allele DPB1*76:01, allele DPB1*78:01, allele DPB1*80:01, allele DPB1*86:01, allele DPB1*88:01, allele DPB1*91:01, allele DPB1*92:01 and allele DPB1*98:01.
In allele DPB1*05:01 and allele DPB1*19:01.
In allele DPB1*08:02, allele DPB1*09:02, allele DPB1*13:01, allele DPB1*13:02 and allele DPB1*19:01.
In allele DPB1*09:01, allele DPB1*10:01, allele DPB1*14:01, allele DPB1*16:02, allele DPB1*17:01, allele DPB1*22:02, allele DPB1*30:01, allele DPB1*35:01, allele DPB1*45:01, allele DPB1*54:01, allele DPB1*55:01, allele DPB1*58:01, allele DPB1*66:01, allele DPB1*67:01, allele DPB1*76:01, allele DPB1*86:01, allele DPB1*91:01 and allele DPB1*98:01; requires 2 nucleotide substitutions.
In allele DPB1*11:01, allele DPB1*15:01, allele DPB1*69:01 and allele DPB1*74:01.
In allele DPB1*14:02 and allele DPB1*21:02.
In allele DPB1*15:01, allele DPB1*18:01, allele DPB1*28:01, allele DPB1*34:01, allele DPB1*40:01, allele DPB1*53:01, allele DPB1*62:01 and allele DPB1*74:01.
In allele DPB1*22:02; requires 2 nucleotide substitutions.
In allele DPB1*31:01 and allele DPB1*34:01.
In allele DPB1*70:01; requires 2 nucleotide substitutions.
In allele DPB1*75:01; requires 2 nucleotide substitutions.
In allele DPB1*82:01 and allele DPB1*85:01.
Ind allele DPB1*11:01, allele DPB1*15:01 and allele DPB1*74:01.
Asymmetric dimethylarginine; by PRMT1 and PRMT5
Set1/Ash2 histone methyltransferase complex subunit ASH2
Vasoactive intestinal polypeptide receptor 2
Abolishes N-glycosylation; when associated with A-410 and A-422.
Abolishes N-glycosylation; when associated with A-410 and A-432.
Abolishes N-glycosylation; when associated with A-422 and A-432.
Abolishes proton transport, but not chloride transport. Strongly increases anion current; when associated with S-576.
In CONRIBA; strongly slowed gating and increased current amplitudes.
Increases the nitrate/chloride conductance ratio.
Strongly increases anion current; when associated with A-200.
Associated with short sleep phenotype; abolishes inhibition of CLOCK-BMAL1 and NPAS2/BMAL1 transactivation activities.
Associated with short sleep phenotype; heterogeneous phenotype; increases inhibition of CLOCK-BMAL1 and NPAS2/BMAL1 transactivation activities.
Class E basic helix-loop-helix protein 41
NACHT, LRR and PYD domains-containing protein 8
In NSDVS1; gain-of-function, reduced BET proteins stability.
In NSDVS2; dominant-negative, increased BET proteins stability.
Strongly reduced affinity for substrate proteins.
Strongly reduced homodimerization. Reduces the activity of the cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex.
In CCF; reduces the ability to transactivate a luciferase reporter gene; suppresses wild-type activity in a dose-dependent manner.
Found in a patient with Rett syndrome-like phenotype; unknown pathological significance.
In VWM; with and without ovarian failure.
Translation initiation factor eIF-2B subunit beta
Pseudouridylate synthase TRUB2, mitochondrial
Decreased activation of transcription from PGF and C3 promoters.
Increased activation of transcription from the C3 promoter but no effect on the PGF promoter.
Monofunctional C1-tetrahydrofolate synthase, mitochondrial
Loss of cross-link to SUMO1. Abolishes association with nuclear pores during interphase, and with mitotic spindles during mitosis.
Strongly decreased phosphorylation. No effect on sumoylation.
In one patient with acute myeloid leukemya; somatic mutation.
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1
Abolishes dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.
Decreases dehydrogenase activity. Loss of proteolytic activity.
Dihydrolipoyl dehydrogenase, mitochondrial
Does not affect dihydrolipoyl dehydrogenase activity.
In DLDD; loss of enzyme activity; abolished interaction with PDHX.
In DLDD; loss of enzyme activity; reduced interaction with PDHX.
In DLDD; no effect on interaction with PDHX.
In DLDD; reduced dehydrogenase activity; increased proteolytic activity.
In DLDD; reduced dihydrolipoyl dehydrogenase activity; no effect on interaction with PDHX.
Loss of dehydrogenase activity. Increases proteolytic activity.
Loss of proteolytic activity. Does not affect dehydrogenase activity.
Reduces dihydrolipoyl dehydrogenase activity.
Reduces dihydrolipoyl dehydrogenase activity. Does not affect interaction with PDHX.
Reduces interaction with PDHX. Inhibits multienzyme pyruvate dehydrogenase complex activity. Does not affect dihydrolipoyl dehydrogenase activity.
Zinc finger and BTB domain-containing protein 42
Methylmalonyl-CoA epimerase, mitochondrial
Does not affect nuclear localization; no loss of transcriptional repression activity; no loss of ability to self-associate; no loss of interaction with FOXP2.
In MRLIAF; nuclear and cytoplasmic aggregation; loss of transcriptional repression activity; loss of ability to self-associate; loss of interaction with FOXP2.
In MRLIAF; unknown pathological significance; does not affect nuclear localization; no loss of transcriptional repression activity; no loss of ability to self-associate; no loss of interaction with FOXP2.
Likely benign variant; does not affect nuclear localization; no loss of transcriptional repression activity; no loss of ability to self-associate; no loss of interaction with FOXP2.
2-fold decrease in enzyme efficiency, as determined by kcat/KM ratio, and efficiently inhibited by chlorzolamide; when associated with Q-67.
2-fold decrease in enzyme efficiency, as determined by kcat/KM ratio, and efficiently inhibited by chlorzolamide; when associated with S-65.
Enhanced p-nitrophenyl acetate esterase activity, but normal CO(2) hydrase activity.
Enhanced proton transfer; when associated with A-64.
Higher affinity for bicarbonate. Enhanced proton transfer capacity; when associated with A-64.
Impaired activity, not rescued by 4-methylimidazole (4-MI).
Impaired activity, not rescued by 4-methylimidazole (4-MI); when associated with W-64.
Impaired activity, rescued by 4-methylimidazole (4-MI). Impaired activity, not rescued by 4-methylimidazole (4-MI); when associated with A-5.
Normal CO(2) hydrase activity, but impaired stability.
Reduced CO(2) hydrase activity, rescued by 4-methylimidazole (4-MI). Reduced proton transfer; when associated with H-62. Enhanced proton transfer; when associated with H-67. Enhanced proton transfer capacity; when associated with H-99.
Reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities.
Reduced proton transfer; when associated with A-64.
Strongly reduced CO(2) hydrase activity.
Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities, impaired stability of zinc binding.
Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities.
Strongly reduced activity and sulfonamide affinity.
Strongly reduced activity, but enhanced zinc affinity.
Leukocyte immunoglobulin-like receptor subfamily A member 1
Affects MPP uptake; reduction of the MPP uptake when associated with V-408.
Affects transporter activity; reduction of the MPP uptake when associated with V-408.
Affects transporter activity; reduction of the TEA uptake; reduction of the MPP uptake when associated with V-408; largely localized to the plasma membrane.
Affects transporter activity; reduction of the serotonin uptake; no MPP uptake when associated with L-160.
Does not affect transporter activity; no changes in the MPP uptake when associated with F-14; no changes in the MPP uptake when associated with F-85; no changes in the MPP uptake when associated with L-189; no changes in the MPP uptake when associated with His-342; no changes in the MPP uptake when associated with M-420 del; no changes in the MPP uptake when associated with I-440; no changes in the MPP uptake when associated with I-461; no changes in the MPP uptake when associated with M-488; reduction of the MPP uptake when associated with C-61; no MPP uptake when associated with V-220; reduction of the MPP uptake when associated with L-341; no MPP uptake when associated with S-401; no MPP uptake when associated with R-465.
Exclusively found in the African American population; increase of the MPP uptake when associated with V-408.
No changes in both TEA and MPP uptake; abolishes MPP uptake when associated with S-401; largely localized to the plasma membrane.
No changes in the MPP uptake when associated with V-408.
Reduction of the localization to the basolateral membrane; no MPP uptake when associated with V-408.
Voltage-dependent calcium channel gamma-3 subunit
Abolishes binding to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid and the localization to the loose actin filament arrays.
Affects targeting to loose actin filament arrays.
Reduced binding to phosphatidylinositol 3,4-bisphosphate and reduced association with actin filament.
Abolishes manganese efflux activity; when associated with A-127.
Abolishes manganese efflux activity; when associated with A-244.
Decreases interaction with SLC30A3; no effect on self-association; decreases zinc transport; decreases EGF-induced ERK1/2 phosphorylation.
In HMNDYT1; abolishes cell surface localization.
In HMNDYT1; abolishes cell surface localization; decreases manganese efflux; decreases protection against manganese-induced neurotoxity.
In NPHP9; a full-length mouse NEK8 construct containing the mutation shows a defect in ciliary localization with no apparent effect on ciliation, mitosis or centriole number.
Abolishes 3-phosphoinositide-binding; when associated with E-56.
Abolishes 3-phosphoinositide-binding; when associated with E-58.
Reduces AR-induced nuclear translocation.
Reduces affinity for KLRF2 over 10'000-fold.
Growth hormone-releasing hormone receptor
In IGHD4; reduced cAMP response to GHRH.
Notch homolog 2 N-terminal-like protein A
Notch homolog 2 N-terminal-like protein C
Leukocyte immunoglobulin-like receptor subfamily A member 4
In PARK; sporadic case; unknown pathological significance; results in decreased synaptic vesicle trafficking.
In PARK; unknown pathological significance; results in decreased synaptic vesicle trafficking.
Strongly reduced guanine nucleotide exchange factor activity toward RAB31; when associated with A-825.
Strongly reduced guanine nucleotide exchange factor activity toward RAB31; when associated with A-828.
In a pancreatic ductal adenocarcinoma sample; somatic mutation.
Cytoplasmic dynein 1 light intermediate chain 1
Abolishes phosphorylation by IKKB and reduces cell growth.
In NATD; decreased protein stability; strong decrease in N-terminal acetylation activity in vitro.
In NATD; reduced N-terminal acetyltransferase activity; impaired interaction with NAA15 and NAA50; does not affect cytoplasmic localization.
In NATD; reduced monomeric N-terminal acetyltransferase activity in vitro.
Loss of its ability to acetylate HSPA1A and HSPA1B.
Disintegrin and metalloproteinase domain-containing protein 12
Cytochrome c oxidase subunit 8C, mitochondrial
Decreases affinity for UAF1 by 2 orders of magnitude.
Decreases affinity for UAF1 by 3 orders of magnitude.
Antagonist of the chemokine receptors CCR1 and CCR3.
No effect on inhibition of activity by tick evasin-4.
Reduced inhibition of activity by tick evasin-4.
Abolishes cleavage of mitochondrial transit peptide.
Nearly abolishes enzyme activity. Strongly reduced affinity for myristoyl-CoA.
Mislocalization to the cytosol; induces apoptotic cell death.
Putative lipoyltransferase 2, mitochondrial
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-503, A-505, A-518, A-572 and A-579.
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-503, A-505, A-518, A-572 and A-584.
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-503, A-505, A-518, A-579 and A-584.
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-503, A-505, A-572, A-579 and A-584.
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-503, A-518, A-572, A-579 and A-584.
Greatly impairs in vitro phosphorylation by CK2 and impairs cell cycle regulation activity; when associated with A-505, A-518, A-572, A-579 and A-584.
SH3-containing GRB2-like protein 3-interacting protein 1
Does not interact with HCFC1 and is inefficient at inhibiting CREB3 transcriptional activity. Does not colocalize with CREB3 in promyelocytic leukemia protein nuclear bodies (PML-NB).
Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1021, G-1024 and G-1032.
Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1021, L-1029 and G-1032.
Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1024, L-1029 and G-1032.
Disrupts interaction with Rab7and no localization to endososmal membranes; when associated with G-1021, G-1024 and L-1029.
In OPTA3; unknown pathological significance.
No effect on interaction with ARL8B. No effect on interaction with RAB7A.
Pleckstrin homology domain-containing family M member 1
Reduces interaction with ARL8B. No effect on interaction with RAB7A. Loss of interaction with ARL8B as well as late endosome and lysosome clustering; when associated with A-60.
Strongly reduces interaction with ARL8B. No effect on interaction with RAB7A. No effect on late endosome and lysosome clustering. Loss of interaction with ARL8B as well as late endosome and lysosome clustering; when associated with 119-A--A-123.
Leucine-rich repeat-containing protein 55
Membrane-spanning 4-domains subfamily A member 12
Activity is restricted HECT-type and not RING-containing E3 ubiquitin-protein ligases. Exhibits ubiquitin transfer with ARIH1 and PRKN.
Strongly impairs lysine reactivity but retains some ability to transfer ubiquitin to BRCA1.
Golgi-associated plant pathogenesis-related protein 1
In NPHP18; accumulates in the nucleus; does not interact with CEP164 and IFT20.
In NPHP18; does not affect interaction with CEP164 and IFT20.
In NPHP18; does not interact with CEP164 and IFT20.
Bipartite nuclear localization signal (NLS1)
Nuclear receptor subfamily 4 group A member 2
Dominant-negative mutant, no effect on IGFR1-binding, defective in integrin-binding and the formation of ternary complex with integrins and IGFR1, defective in inducing IGF1 signaling and cell proliferation, and suppresses activation of IGF1R by insulin and tumorigenesis in vivo; when associated with E-84.
Dominant-negative mutant, no effect on IGFR1-binding, defective in integrin-binding and the formation of ternary complex with integrins and IGFR1, defective in inducing IGF1 signaling and cell proliferation, and suppresses activation of IGF1R by insulin and tumorigenesis in vivo; when associated with E-85.
Found in a patient with primordial dwarfism; unknown pathological significance.
Serine/threonine-protein phosphatase 6 regulatory subunit 3
In NSLH2; unknown pathological significance.
Serine/threonine-protein phosphatase PP1-beta catalytic subunit
Mitochondrial basic amino acids transporter
Glutaredoxin-related protein 5, mitochondrial
In SIDBA3; deficiency in Fe-S cluster synthesis; does not impair ISCU binding.
In SPAHGC; no effect on protein abundance in patient cells; probably reduced activity in iron-sulfur cluster assembly that results in reduced production of the lipoate cofactor and protein lipoylation.
Elevated Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Increases apoptotic activity.
Loss of activity, apoptotic function and of autophosphorylation.
Loss of phosphorylation and significant increase in proapoptotic activity.
Reduced Ca(2+)-calmodulin binding and Ca(2+)-calmodulin-independent kinase activity. Decreases apoptotic activity.
In isoform 2, isoform 3, isoform 5 and isoform 6.
In N-gly,C; does not creates a N-glycosylation site.
In N-gly,N; creates a N-glycosylation site.
Constitutively activated. Promotes formation of actin stress fibers.
Decreased activation of kinase activity.
Decreased phosphorylation. Nearly abolishes stimulation of insulin secretion.
Loss of catalytic activity. Causes disintegration of actin stress fibers.
Prevents phosphorylation and activation by STK11/LKB1 complex.
Cation channel sperm-associated protein 1
Sorting and assembly machinery component 50 homolog
Constitutively active mutant locked in the active GTP-bound form.
In WSMN; impaired localization to cytoplasmic vesicles.
In WSMN; loss of function mutation; expression of the mutation in neuroblastoma cells results in low levels of the mutant protein.
In CMAVM1; unknown pathological significance.
Lysosomal-associated transmembrane protein 4A
Associated with increase in hair thickness; results in decreased downstream activity of NFKB1 48 hours after transfection into cells.
In ECTD10A and ECTD10B; abolishes NF-kappa-B activation and reduces JNK activation.
In ECTD10B; the mutant protein does not interact with EDARADD and is functionally inactive.
Tumor necrosis factor receptor superfamily member EDAR
Found in a patient with azoospermia; unknown pathological significance.
In CADASIL2; loss of proteolytic activity.
In CADASIL2; partial loss of proteolytic activity.
In CADASIL2; unknown pathological significance; small decrease, if any, in proteolytic activity.
In CARASIL; has 21 to 50% normal protease activity; is unable to suppress TGF-beta activity.
Slightly decreased O-methyltransferase activity.
Strongly decreased O-methyltransferase activity.
Disrupts interaction with RBX1. Loss of inhibition of SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase activity.
In GVMs; loss of interaction with CUL1 and RBX1.
Loss of interaction with FKBP4 and FKBP1A.
Vacuolar protein sorting-associated protein VTA1 homolog
Abolishes single and double sumoylation; nuclear localization conserved. Increases transcriptional activity and inhibits repression domain activity; when associated with R-263 and R-353.
Decreases sumoylation; Abolishes double sumoylation only; Nuclear localization conserved. Increases transcriptional activity and inhibits repression domain activity; when associated with R-244 and R-353.
Inhibition of KPNA2 interaction when mutation occurs in the NLS; decreased nuclear import with localization in the nucleus but also in the cytoplasm; Complete inhibition of nuclear import when associated with a lack of zinc-finger domains.
No effect on sumoylation. Increases transcriptional activity and inhibits repression domain activity; when associated with R-244 and R-263.
No effect on transcription activation capacity.
No inhibition of KPNA2 interaction and no change in nuclear import.
Prevents formation of functional zinc-finger 3; induces drastic decrease of DNA affinity and complete modification of DNA binding specificity.
Prevents formation of functional zinc-finger 7 and inhibits DNA binding; No proliferation and transformation of cultured cells.
Abolishes interaction with TNPO1, TNPO1-mediated nuclear import and nuclear location.
Decreased nuclear and partially cytoplasmic location.
Disrupts nuclear localization signal. No effect on RNA binding.
Disrupts the bi-partite nuclear localization signal and abolishes nuclear location.
Disrupts the bi-partite nuclear localization signal and abolishes nuclear location; when associated with N-716 and N-723.
Disrupts the bi-partite nuclear localization signal and abolishes nuclear location; when associated with N-716 and S-719.
Disrupts the bi-partite nuclear localization signal and abolishes nuclear location; when associated with S-719 and N-723.
Double-stranded RNA-specific adenosine deaminase
No effect on nuclear location. No effect on RNA binding.
No effect on nuclear location; when associated with A-718 and A-721.
No effect on nuclear location; when associated with A-721 and A-724.
Strongly impaired RNA binding. No effect on nuclear location.
In HH13; significantly reduced efficacy as well as potency.
Coiled-coil domain-containing protein 14
Mitochondrial mRNA pseudouridine synthase RPUSD3
In CFZS; decreased localization at the plasma membrane; reduced cell fusion in a heterologous cell fusion assay in vitro compared to wild-type; partially rescues of mymk knockout fish.
In CFZS; loss of localization at the plasma membrane; loss of cell fusion in a heterologous cell fusion assay in vitro; no rescue of mymk knockout fish.
In CFZS; loss of localization at the plasma membrane; loss of cell fusion in a heterologous cell fusion assay in vitro; no rescue of mymk knockout fish; primary myoblasts from a compound heterozygote associating T-91 and R-185 exhibit no difference in their capability to differentiate compared to control myoblasts, but show a significant difference in the fusion index, with a higher percentage of singly-nucleated relative to multinucleated cells in compound heterozygous compared to control myoblasts.
In CFZS; unknown pathological significance.
In CFZS; unknown pathological significance; supports cell fusion in a heterologous cell fusion assay in vitro; decreased localization at the plasma membrane; partially rescues of mymk knockout fish; primary myoblasts from a compound heterozygote associating T-91 and R-185 exhibit no difference in their capability to differentiate compared to control myoblasts, but show a significant difference in the fusion index, with a higher percentage of singly-nucleated relative to multinucleated cells in compound heterozygous compared to control myoblasts.
Abolishes ATPase activity without affecting its role in DNA damage response; when associated with A-668.
Abolishes ATPase activity without affecting its role in DNA damage response; when associated with M-605.
Abolishes ATPase activity, leading to abolish ability to inhibit DNA replication without affecting subcellular location.
Short transient receptor potential channel 7
Less than 3% of wild-type activity using succinamate as substrate.
Loss of activity using succinamate as substrate.
Does not affect thromboxane-A synthase activity. Does not affect heme-binding.
In allele CYP5A1*5; KM value about 1.5 higher for PEG2; Vmax/KM approximately 27% of that of the wild-type.
In allele CYP5A1*6; does not affect KM value for PEG2; does not affect Vmax/KM value.
In allele CYP5A1*7; does not affect KM value for PEG2; does not affect Vmax/KM value.
In allele CYP5A1*8; KM value about 1.5 higher for PEG2; Vmax/KM approximately 56 % of that of the wild-type.
Loss of thromboxane-A synthase activity. Decreased heme-binding.
The KM value is about 1.5 higher for PEG2; in allele CYP5A1*5; KM value about 1.5 higher for PEG2; Vmax/KM approximately 50% of that of the wild-type.
Complete loss of phosphorylation in response to LPS.
Loss of ability to dimerize. Loss of RANTES-inducing activity and ability to induce NF-kappa-B activation. Inhibition of TLR4-dependent activation of IRF3 and IRF7. Loss of interaction with TLR4.
Loss of ability to dimerize. Significant loss of RANTES-inducing activity. Loss of ability to induce NF-kappa-B activation.
Loss of phosphorylation. Abolishes ability to activate IRF3 or NF-kappa-B and to transduce TLR4 signal.
Loss of phosphorylation. Significant reduction in the ability to activate IRF3 or NF-kappa-B.
No effect on phosphorylation and on the ability to activate IRF3 or NF-kappa-B.
Results in relocalization from membrane to cytosol; Loss of ability to transduce TLR4-signal. Loss of TLR2-mediated activation of IRF7.
Significant decrease of localization in the membrane.
TIR domain-containing adapter molecule 2
Volume-regulated anion channel subunit LRRC8E
Tumor protein p63-regulated gene 1-like protein
In NDCAMA; may drastically decrease protein expression level.
Iron-responsive element-binding protein 2
Transmembrane ascorbate-dependent reductase CYB561
Abolishes binding to PKA-RI; when associated with 438-P-P-439.
Abolishes binding to PKA-RI; when associated with 445-P-P-446.
WD repeat, SAM and U-box domain-containing protein 1
General transcription and DNA repair factor IIH helicase subunit XPB
In XP-B; combined with features of Cockayne syndrome; mild.
No transcriptional activity of the reconstituted TFIIH complex.
Echinoderm microtubule-associated protein-like 2
BRD4-interacting chromatin-remodeling complex-associated protein
In CSS12; unknown pathological significance.
Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-181 or E-185. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-181 and E-185.
Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-181 or E-187. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-181 and E-187.
Defective in integrin-binding and in inducing ERBB3 phosphorylation; when associated with or without E-185 or E-187. No effect on ERBB3-binding, defective in integrin-binding and in ternary complex formation with ERBB3 and integrins, and defective in inducing NRG1-ERBB signaling; when associated with E-185 and E-187.
Pro-neuregulin-1, membrane-bound isoform
Abolishes the deubiquitinating enzyme activity.
In IDDFSDA; unknown pathological significance.
In ALS25; unknown pathological significance.
In SPG10; decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover.
In SPG10; does not affect microtubule affinity; does not affect gliding velocity; does not affect microtubule-dependent ATP turnover.
In SPG10; slightly decreases microtubule affinity; reduces gliding velocity; reduces microtubule-dependent ATP turnover.
Strongly reduces microtubule affinity; slightly reduces gliding velocity.
Tigger transposable element-derived protein 5
Abolishes almost completely the SRC-induced phosphorylation of BMX.
Phosphotyrosine; by SRC and autocatalysis
Loss of monoubiquitination; when associated with R-15.
Loss of monoubiquitination; when associated with R-24.
Stabilizes the protein in G1 by preventing association with the APC/C complex and degradation by the proteasome.
1000-fold reduction in activity, inhibits equally PP1 and PP2A.
Protein phosphatase 1 regulatory subunit 1A
Decreased rate of activity and decreased zinc binding.
Loss of activity. Loss of ubiquitin binding; when associated with A-221. Lower affinity for triubiquitin and tetraubiquitin, but no effect on affinity for diubiquitin; when associated with E-666. Lower affinity for diubiquitin, triubiquitin and tetraubiquitin; when associated with E-734.
Loss of polyubiquitin binding and hydrolysis.
Loss of polyubiquitin binding and subsequent activation.
Loss of polyubiquitin hydrolysis. Loss of ubiquitin binding; when associated with A-335.
Lower affinity for diubiquitin, triubiquitin and tetraubiquitin; when associated with A-335. No effect on activity; when associated with E-666.
Lower affinity for triubiquitin and tetraubiquitin, but no effect on affinity for diubiquitin; when associated with A-335. No effect on activity; when associated with E-734.
In BWS; unknown pathological significance.
Integrin-linked kinase-associated serine/threonine phosphatase 2C
Reduced MCM complex DNA helicase activity. No effect on MCM complex formation. No effect on MCM complex ssDNA binding and ATPase activity.
Abrogates binding to EPPIN and do not inhibit spem motility.
Does not affect conductance and gating properties of the channel.
Does not affect gating properties of the channel.
In MTDPS6 and CMT2EE; results in incomplete closing of the channel.
In MTDPS6; does not completely rescue iridophores loss in zebrafish 'tra' mutants; may cause protein instability and decay.
In MTDPS6; results in altered ribonucleotide incorporation in mtDNA from patient fibroblasts.
In MTDPS6; unknown pathological significance.
Putative uncharacterized protein C8orf89
In FFEVF1; does not inhibit DEPDC5 signaling; does not change kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.
In FFEVF1; does not inhibit DEPDC5 signaling; does not change kinase activity of mTORC1; does not change association with the GATOR complex; inhibits slightly RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.
In FFEVF1; does not inhibit DEPDC5 signaling; stimulates slightly kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.
In FFEVF1; inhibits slightly DEPDC5 signaling; does not change kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.
In FFEVF1; inhibits slightly DEPDC5 signaling; stimulates slightly kinase activity of mTORC1; does not change association with the GATOR complex; does not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation.
In FFEVF1; unknown pathological significance.
No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-1065, R-1088 and R-1574.
No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1065 and R-1574.
No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-447, R-710, R-1088 and R-1574.
No effect on ubiquitination. Loss of interaction with KLHL22 and ubiquitination; when associated with R-710, R-1065, R-1088 and R-1574.
No effect on ubiquitination. Loss of ubiquitination; when associated with R-447, R-710, R-1065 and R-1088.
Ubiquitin carboxyl-terminal hydrolase 29
In FRUCT; loss of ketohexokinase function; insoluble.
In FRUCT; no effect on ketohexokinase function; decreases enzyme activity but no effect in substrate affinity; decreases thermal stability.
Loss of PLA2 activity toward PAF. Impairs anti-adenoviral activity.
In NEDHCAS; unknown pathological significance.
In Baltimore-3; impaired polymerization.
In CAFBN; hypofibrinogenemia; heterozygous.
In CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; decreased fibrinogen complex secretion.
In CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; impaired fibrinogen complex secretion.
In CAFBN; hypofibrinogenemia; heterozygous; no effect on fibrinogen complex assembly; no effect on fibrinogen complex secretion.
In DYSFIBRIN; fibrinogen Baltimore-1; impaired polymerization.
In DYSFIBRIN; fibrinogen Bergamo-2/Essen/Haifa/Osaka-3/Perugia/Saga/Barcelona-3/Barcelona-4.
In DYSFIBRIN; fibrinogen Milano-1; impaired polymerization.
In Hillsborough; prolonged thrombin clotting time.
In Kyoto-1; causes accelerated cleavage by plasmin.
In Tochigi/Osaka-2/Milano-5/Villajoyosa.
In Vlissingen; defective calcium binding and impaired polymerization.
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-432)
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-424)
N-linked (GlcNAc...) asparagine; in variant Asahi
Decreases glycosylation levels. Abolishes glycosylation; when associated with A-159.
Decreases glycosylation levels. Abolishes glycosylation; when associated with A-194.
Adipocyte plasma membrane-associated protein
Abolished phosphorylation and interaction with PPP3CA.
Loss of phosphorylation. No effect on the binding of GDP or GTP. Localizes primarily to the Golgi complex but does not affect membrane localization.
Phosphomimetic mutant. No effect on the binding of GDP or GTP. Loss of GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, RAB3IP, TBC1D15, and INPP5B binding. Increases localization to the cell membrane.
Probable constitutively active mutant locked in the active GTP-bound form. Stimulates interaction with MICALL1.
In MT-C4D; affect the stability of the COX complex.
Abolished ATPase activity without affecting ability to activate the MAVS-dependent signaling to produce interferon-beta.
Decreased, but not abolished interaction, with NKRF.
Abolishes ER stress-induced JNK activation and apoptosis.
Abolishes ER stress-induced JNK activation and apoptosis. Abolishes interaction with ERN1. Does not affect localization to endoplasmic reticulum.
Abolishes ER stress-induced JNK activation and apoptosis. Disrupts localization to endoplasmic reticulum.
Complete loss of E3 ligase activity; when associated with A-258.
Complete loss of E3 ligase activity; when associated with A-260.
Found in a tumor sample; unknown pathological significance; abolished ability to regulate protein trafficking and localization.
Found in a tumor sample; unknown pathological significance; abolished localization to endosomes.
In DEE73; gain-of-function variant; increased ER stress-induced apoptosis.
No effect on ER stress-induced JNK activation and apoptosis.
No effect on ER stress-induced JNK activation and apoptosis. No effect on interaction with ERN1.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-107; E-110; E-114; E-132 and E-134.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-107; E-110; E-114; E-132 and E-136.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-107; E-110; E-114; E-134 and E-136.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-107; E-110; E-132; E-134 and E-136.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-107;E-114; E-132; E-134 and E-136.
Abolishes ability to induce membrane remodeling in the presence of CBY1; when associated with E-110; E-114; E-132; E-134 and E-136.
CBY1-interacting BAR domain-containing protein 1
In PAPA9; does not form homodimers; does not interact with CBY1; does not localize to cilium basal body.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-107 and A-109.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-107 and A-110.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-109 and A-110.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-132 and A-134.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-132 and A-136.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-134 and A-136.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-264 and A-266.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-264 and A-267.
Reduced membrane-binding and significant reduction in membrane remodeling activity; when associated with A-266 and A-267.
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha'
In ACHM5; decreases cGMP phosphodiesterase activity.
In ACHM5; severely decreases cGMP phosphodiesterase activity.
In COD4 and ACHM5; severely decreases cGMP phosphodiesterase activity.
No effect on cGMP phosphodiesterase activity.
Abolishes binding to monomethylated and dimethylated peptides.
Abolishes binding to monomethylated and dimethylated peptides. Abolishes binding to p53/TP53 monomethylated at 'Lys-382'.
Abolishes binding to p53/TP53 monomethylated at 'Lys-382'.
Does not affect binding to monomethylated and dimethylated peptides.
Lethal(3)malignant brain tumor-like protein 1
Strongly impairs binding to monomethylated and dimethylated peptides.
Strongly impairs binding to monomethylated and dimethylated peptides. Abolishes binding to p53/TP53 monomethylated at 'Lys-382'.
28S ribosomal protein S10, mitochondrial
Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-561 and A-596.
Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-561 and A-599.
Loss of catalytic activity but does not affect its capacity to inhibit ITCH catalytic activity; when associated with A-596 and A-599.
Loss of catalytic activity. Loss of histone H2B ubiquitination. No effect on STAT1 phosphorylation and on the interaction with PARP9 and STAT1.
Does not improve solubility; when associated with R-108, R-205, R-235 and R-250.
Does not improve solubility; when associated with R-73, R-108, R-205 and R-235.
Does not improve solubility; when associated with R-73, R-108, R-205 and R-250.
Does not improve solubility; when associated with R-73, R-108, R-235 and R-250.
Does not improve solubility; when associated with R-73, R-205, R-235 and R-250.
SLIT-ROBO Rho GTPase-activating protein 2C
Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5
Coiled-coil domain-containing protein 43
In FHL5; leads to a complete loss of the ability to interact with STX11.
In isoform 2, isoform 4, isoform 6 and isoform 9.
Mimicks a phosphorylated state and impairs interaction with SNCA.
BMP/retinoic acid-inducible neural-specific protein 1
Almost complete loss of catalytical activity.
Complete loss of catalytical activity. Complete loss of catalytical activity; when associated with F-306.
Loss of catalytic activity. Complete loss of catalytic activity; when associated with A-101.
Strongly reduces histone deacetylase activity.
Abolishes deubiquitinating activity. Does not abolish ability to stabilize SIAH2. Does not abolish ability to stabilize SIAH2; when associated with A-814 and A-823.
Does not abolish ability to stabilize SIAH2.
Does not abolish ability to stabilize SIAH2; when associated with A-345 and A-814.
Does not abolish ability to stabilize SIAH2; when associated with A-345 and A-823.
Impairs ability to stabilize SIAH2. Abolishes ability to stabilize SIAH2; when associated with E-664.
Impairs ability to stabilize SIAH2. Abolishes ability to stabilize SIAH2; when associated with E-739.
Ubiquitin carboxyl-terminal hydrolase 13
Cytochrome c oxidase assembly factor 4 homolog, mitochondrial
Abrogates interaction with HCST and TYROBP.
Coiled-coil domain-containing protein 15
Almost complete loss of in vitro methylation by METTL22.
N6,N6,N6-trimethyllysine; by METTL22; in vitro
Significant reduction of RNA-binding activity.
Ral guanine nucleotide dissociation stimulator-like 3
Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced ROS generation, which may decrease resistance to infection by enteric pathogens, such as Escherichia coli.
In TDH6; the enzyme is non-functional; expressed at the cell surface of cells albeit at low level.
In one patient with familial myopathy; unknown pathological significance.
U3 small nucleolar RNA-associated protein 14 homolog C
In MCPH2; the mutant protein does not localize to the spindle pole during mitosis.
In MCPH2; uncertain pathological significance.
In HH1; phenotype consistent with Kallmann syndrome.
In HH1; phenotype consistent with Kallmann syndrome; loss of effect on the migratory activity of GnRH neurons; Reduced FGFR1-binding.
In HH1; phenotype consistent with Kallmann syndrome; loss of effect on the migratory activity of GnRH neurons; complete loss of FGFR1-binding.
In HH1; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; the patient also carries a mutation in FGFR1.
Probable disease-associated variant found in a patient with Kallmann syndrome; the patient also carries mutation Ala-688 in SEMA3A.
Potassium voltage-gated channel subfamily E member 4
A disintegrin and metalloproteinase with thrombospondin motifs 13
Abolishes pro-domain removal but no loss of proteolytic activity; when associated with D-73.
Abolishes pro-domain removal but no loss of proteolytic activity; when associated with K-71.
Does not affect protein secretion; normal proteolytic activity.
Dramatically reduced affinity for calcium.
Found in a patient with hemolytic uremic syndrome.
In TTP; affects protein secretion; the mutant protein has reduced protease activity.
In TTP; impairs protein secretion and proteolytic activity.
In TTP; impairs protein secretion; the mutant protein has reduced protease activity.
In TTP; mild effect on protein secretion; strong reduction of proteolytic activity.
In TTP; reduces protein secretion and proteolytic activity.
In a patient with thrombotic thrombocytopenic purpura.
No change in calcium dependence for proteolysis.
No effect on cleavage of VWF and greatly reduced secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-965.
No effect on cleavage of VWF and greatly reduced secretion of ADAMTS13. Abolishes secretion of ADAMTS13; when associated with A-399.
No effect on cleavage of VWF and little change in secretion of ADAMTS13.
No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-1027.
No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-1087.
No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes most of the secretion of ADAMTS13; when associated with A-907.
No effect on cleavage of VWF and little change in secretion of ADAMTS13. Abolishes secretion of ADAMTS13; when associated with A-698.
Mitogen-activated protein kinase kinase kinase 12
Peptidyl-prolyl cis-trans isomerase A-like 4G
NADPH:adrenodoxin oxidoreductase, mitochondrial
Abolishes interaction with RSPO1 and prevents subsequent membrane clearance.
In allele TF*C3; associated with a reduction in total iron binding capacity; risk factor for iron deficiency anemia in menstruating white women.
N-linked (GlcNAc...) asparagine; atypical; partial
In KFS3 and MCOPCB6; reduces the amount of active ligand secreted; reduced amout of mature protein in the cytosol.
In MCOP7; also detected in a patient with bilateral iris coloboma; reduces the amount of active ligand secreted.
In MCOP7; reduces the amount of active ligand secreted.
In a non-small cell lung cancer cell line.
Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase
Enzyme activity is 19% of the wild-type.
Enzyme activity is 20% of the wild-type. A 10-fold increase in Km value for ganglioside GM3. A 5-fold decrease in Vmax for both CMP-N-acetyl-beta-neuraminate and ganglioside GM3.
Enzyme activity is 33% of the wild-type. A 2-fold increase in Km value for ganglioside GM3 and 1.25 fold increase in Km value for CMP-N-acetyl-beta-neuraminate. A 3-fold decrease in Vmax for both CMP-N-acetyl-beta-neuraminate and ganglioside GM3.
Enzyme activity is 42% of the wild-type. A 2.5-fold increase in Km value for CMP-N-acetyl-beta-neuraminate. A 2.3-fold decrease in Vmax for both CMP-N-acetyl-beta-neuraminate and ganglioside GM3.
Enzyme activity is 91% of the wild-type.
Enzyme activity is 98% of the wild-type.
In MC4DN17; low steady-state levels of COX subunits and reduced levels of fully assembled COX; highly decreased COX complex IV activity and decreased COX complex II activity in muscle.
In MC4DN17; unknown pathological significance.
Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-572.
Abolishes interaction with SRC-family members and impairs internalization of the activated receptor; when associated with F-574.
In GIST sample; constitutively activated kinase.
In GISTPS; increased platelet-derived growth factor alpha-receptor activity; constitutively activated kinase.
In GISTPS; unknown pathological significance.
In a GIST sample; constitutively activated kinase.
In a GIST sample; imatinib resistant, constitutively activated kinase.
In a GIST sample; imatinib sensitive, constitutively activated kinase.
In a hypereosinophilic syndrome sample; constitutively activated kinase.
In a hypereosinophilic syndrome sample; does not lead to constitutive kinase activation.
No effect on autophosphorylation and phosphorylation of PLCG1. Abolishes activation of phosphatidylinositol 3-kinase.
Platelet-derived growth factor receptor alpha
Strongly reduced interaction with PTPN11 and GRB2.
Trafficking protein particle complex subunit 13
ATP-sensitive inward rectifier potassium channel 8
Found in Brugada syndrome and other J-wave syndromes; unknown pathological significance; the mutant channel displays an increase in glibenclamide-sensitive potassium currents compared to wild type.
In HTOCD; unknown pathological significance; displays gain of function; displays reduced ATP sensitivity.
In HTOCD; unknown pathological significance; displays gain of function; increased open state stability, reduced sensitivity to ATP inhibition and increased channel activity; almost completely abolishes high affinity sensitivity to glibenclamide, an inhibitor of ATP-sensitive potassium channels.
In SIDS; the mutant channel displays reduced potassium currents compared to wild type.
In CILD40; associated in cis with E-1881; no protein detected by Western blot when associated with E-1881; loss of localization to cilium axonema when associated with E-1881.
In CILD40; associated in cis with H-2965; no protein detected by Western blot when associated with H-2965; loss of localization to cilium axonema associated with H-2965.
In CILD40; loss of localization to cilium axonema.
In CILD40; unknown pathological significance.
AT-rich interactive domain-containing protein 1B
Found in a patient with short stature; unknown pathological significance.
Probable disease-associated variant found in a patient with short stature; de novo mutation.
In an ovarian clear cell adenocarcinoma.
In an uterine cancer sample; somatic mutation.
Heparan sulfate glucosamine 3-O-sulfotransferase 4
Associated with obesity; abrogates the ability of WNT10B to activate canonical Wnt signaling and blocks adipogenesis.
In STHAG8; reduced activation of Wnt signaling; reduced endothelial differentiation.
(Microbial infection) N6-stearoyl lysine
Constitutively active mutant locked in the active GTP-bound form. Impairs transports of cargo from the trans-Golgi network to the recycling endosomes and alters the assembly of functional tight junctions.
In 3KR mutant; abolished stearoylation in response to S.flexneri infection.
Abolishes the NF-kappa-B inhibitory activity.
Caspase recruitment domain-containing protein 19
Abolishes secretion. No effect on multimer formation.
No effect on secretion. Affects multimer formation.
Zinc finger protein with KRAB and SCAN domains 8
Extracellular tyrosine-protein kinase PKDCC
BTB/POZ domain-containing protein KCTD18
Histidine-rich carboxyl terminus protein 1
Enhanced phosphorylation at Thr-336 and Ser-428, enhanced cytoplasmic localization and increased kinase activity.
Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-204.
In PJS; abolishes kinase activity, leading to loss of autophosphorylation.
In PJS; late onset suggests reduced penetrance.
In PJS; loss of kinase activity, leading to greatly reduced autophosphorylation; fails to phosphorylate PTEN in vitro; no significant effect on nucleocytoplasmic localization.
In PJS; pathogenicity uncertain; no effect heterotrimeric complex assembly with STRADA and CAB39.
In TGCT; a tumor with seminoma and teratoma components; associated with severely impaired but detectable kinase activity; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; predominantly nuclear localization.
In cervical carcinoma; somatic mutation.
In colorectal cancer; no effect heterotrimeric complex assembly with STRADA and CAB39.
In colorectal cancer; somatic mutation; impaired kinase activity.
In colorectal cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39.
In colorectal cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39.
In gastric carcinoma; no effect heterotrimeric complex assembly with STRADA and CAB39.
In melanoma; sporadic malignant; somatic mutation.
In sporadic cancer; somatic mutation; Loss of kinase activity.
In sporadic cancer; somatic mutation; does not affect kinase activity.
In sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39.
In sporadic cancer; somatic mutation; impairs heterotrimeric complex assembly with STRADA and CAB39; requires 2 nucleotide substitutions.
In sporadic cancer; somatic mutation; no effect heterotrimeric complex assembly with STRADA and CAB39.
In sporadic cancer; somatic mutation; no effect on kinase activity nor in heterotrimeric complex assembly with STRADA and CAB39.
Loss of kinase activity, leading to greatly reduced autophosphorylation.
Loss of kinase activity, leading to reduced autophosphorylation and acting as a dominant-negative mutant.
No effect on basal nucleocytoplasmic localization, but fails to translocate to the cytoplasm when coexpressed with SIRT1.
No effect. Impaired formation of a heterotrimeric complex with STRADA and CAB39; when associated with A-74.
Phosphoserine; by autocatalysis, PKA, PKC/PRKCZ and RPS6KA1
Phosphothreonine; by ATM and autocatalysis
Loss of POLD3-binding in a yeast two-hybrid assay.
Probable E3 ubiquitin-protein ligase makorin-3
Tumor necrosis factor alpha-induced protein 8-like protein 3
RNA-binding motif protein, Y chromosome, family 1 member A1
RNA-binding motif protein, Y chromosome, family 1 member D
6-fold reduction in affinity for PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does not affect cell membrane localization or affinity for a tyrosine-phosphorylated peptide; when associated with Q-1142 and Q-1155.
6-fold reduction in affinity for PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does not affect cell membrane localization or affinity for a tyrosine-phosphorylated peptide; when associated with Q-1142 and Q-1157.
6-fold reduction in affinity for PtdIns(3,4,5)P3 and reduced IRS1 dephosphorylation but does not affect cell membrane localization or affinity for a tyrosine-phosphorylated peptide; when associated with Q-1155 and Q-1157.
Does not affect affinity for PtdIns(3,4,5)P3. Reduced affinity for tyrosine-phosphorylated peptide.
Does not affect affinity for PtdIns(3,4,5)P3; when associated with Q-1209 and Q-1212.
Does not affect affinity for PtdIns(3,4,5)P3; when associated with Q-1209 and Q-1214.
Does not affect affinity for PtdIns(3,4,5)P3; when associated with Q-1212 and Q-1214.
Loss of tyrosine-protein phosphatase activity. Reduced IRS1 degradation under catabolic conditions. Abolishes inhibition of AKT1 kinase activity. Does not affect disruption of SQSTM1-IRS1 interaction by TNS2. Reduced mTORC1 complex activation.
General transcription factor 3C polypeptide 3
Cell division cycle-associated 7-like protein
Phosphomimetic mutant. Increased interaction with PSIP1; when associated with D-21, D-77 and D-79.
Phosphomimetic mutant. Increased interaction with PSIP1; when associated with D-21, D-77 and D-81.
Phosphomimetic mutant. Increased interaction with PSIP1; when associated with D-21, D-79 and D-81.
Phosphomimetic mutant. Increased interaction with PSIP1; when associated with D-77, D-79 and D-81.
Significant loss of interaction with PSIP1; when associated with A-16. Complete loss of interaction with PSIP1; when associated with A-16, A-72 and A-73.
Significant loss of interaction with PSIP1; when associated with A-17. Complete loss of interaction with PSIP1; when associated with A-17, A-72 and A-73.
Significant loss of interaction with PSIP1; when associated with A-72. Complete loss of interaction with PSIP1; when associated with A-16, A-17 and A-72.
Significant loss of interaction with PSIP1; when associated with A-73. Complete loss of interaction with PSIP1; when associated with A-16, A-17 and A-73.
Abolishes GTP hydrolysis. Impairs mitochondrial division. Reduces peroxisomal abundance.
Abolishes S-nitrosylation. Reduced dimerization and no enhancement of GTPase activity.
Abolishes homodimerization and formation of higher order oligomers.
Abolishes phosphorylation. Reduces interaction with MIEF1 and MIEF2. Promotes mitochondrial fission and cell vulnerability to apoptotic insults. Mostly mitochondrial. Disrupts, in vitro, binding to FIS1.
Decreased localization to the perinuclear region.
Diminishes intramolecular interaction between GTP-middle domain and GED domain but no effect on homooligomerization. Marked reduction in GTPase activity, in vitro. Decreased mitochondrial division.
Does not impair homodimerization and formation of higher order oligomers.
Impairs formation of higher order oligomers, but not homodimerization.
Impairs homodimerization and formation of higher order oligomers.
Impairs intramolecular interactions but not homooligomerization. Does not reduce interaction with MIEF1 and MIEF2. Impairs formation of higher order oligomers but not homodimerization. Unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site. Slight reduction in GTPase activity. Inhibits mitochondrial fission. Retained in the cytoplasm.
In EMPF1; autosomal recessive; impaired mitochondrial membrane fission; hypomorphic mutation retaining partial activity in mitochondrial membrane fission.
In EMPF1; impaired mitochondrial and peroxisomal membrane fission.
In EMPF1; the mutation acts in a dominant-negative manner; defects observed in both mitochondrial and peroxisomal fission; reduced oligomerization, decreased mitochondrial recruitment.
In EMPF1; the mutation acts in a dominant-negative manner; defects observed in mitochondrial fission; significant decrease in mitochondrial respiratory chain complex IV activity.
In EMPF1; the mutation acts in a dominant-negative manner; reduced oligomerization; decreased mitochondrial recruitment; defects observed in mitochondrial fission.
In EMPF1; unknown pathological significance; unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site; presence of concentric cristae and/or increased dense granules in some mitochondria.
In OPA5; changed localization to mitochondrion; impaired mitochondrial membrane fission.
Loss of GTPase activity. Impairs mitochondrial division and induces changes in peroxisome morphology. No effect on oligomerization. Increase in sumoylation by SUMO3.
Loss of activity. Little effect on mitochondrial morphology. Translocated to mitochondria.
Overexpression delays protein secretion. Rescues fragmented or truncated mitochondria in PRKN- or PINK1-depleted cells.
Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-535 and R-558.
Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-535 and R-568.
Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-532; R-558 and R-568.
Some loss of sumoylation in B domain. Complete loss of sumoylation in B domain; when associated with R-535; R-558 and R-568.
Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-597 and R-606.
Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-597 and R-608.
Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-594; R-606 and R-608.
Some loss of sumoylation in the GED domain; Complete loss of sumoylation in the GED domain; when associated with R-597; R-606 and R-608.
Temperature-sensitive. Impairs mitochondrial division.
Unable to homooligomerize. Unable to associate with MIEF2 into filaments forming the tubular structures that wrap around the scission site.
Does not affect selectivity for binding ADP or ATP.
Does not affect selectivity for binding ADP or ATP. Impaired multi-subunit COQ enzyme complex.
Enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo.
In COQ10D4; unknown pathological significance.
Slightly affects selectivity for binding ADP or ATP.
Strongly impairs binding ADP or ATP. Impaired multi-subunit COQ enzyme complex.
Loss of membrane localization. No loss of enzyme activity.
Loss of prenylation and membrane localization. No loss of enzyme activity.
In an ovarian papillary serous adenocarcinoma sample; somatic mutation.
Abolishes binding to TLN2. Affects localization to focal adhesions.
Does not affect binding to TLN2 and localization to focal adhesions.
Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma
SMC5-SMC6 complex localization factor protein 1
In isoform 4, isoform 5, isoform 7 and isoform 10.
Phosphotyrosine; by ABL1 and autocatalysis
Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases
Somatic mutation in a breast cancer sample.
Somatic mutation in a lung squamous cell carcinoma.
Abolishes interaction with ZAP70 and EPHB1, but does not affect interaction with SLA. Reduces ubiquitination and therefore proteasomal degradation of SPRED2.
Found in patients with acute myeloid leukemia; unknown pathological significance.
Found in patients with acute myeloid leukemia; unknown pathological significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis.
In NSLL; dominant-negative; impairs CBL-mediated ubiquitination, internalization and degradation of the EGF receptor/EGFR; decreases the ability to negatively regulate EGFR signaling.
No effect on tyrosine phosphorylation by INSR. Loss of phosphorylation by SRC. Inhibition of bone resorption. Abolishes interaction with PIK3R1.
Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-700.
Strongly reduces tyrosine phosphorylation by INSR; when associated with F-371 and F-774.
Strongly reduces tyrosine phosphorylation by INSR; when associated with F-700 and F-774.
Abolishes phosphorylation of S-990. Impairs the interaction with BRCA1.
Disrupts BRCA1-mediated double-strand break repair. Loss of ATPase and DNA helicase activities.
Does not affect the interaction with BRCA1.
In BC; early onset; loss of ATPase and helicase activities.
In BC; early onset; reduces helicase efficiency on longer substrates.
In FANCJ; destabilizes iron-sulfur-binding and abolishes helicase activity.
In a patient with ovarian cancer; unknown pathological significance.
Ubiquitin carboxyl-terminal hydrolase 26
In DBA19; unknown pathological significance.
In FA2D; prothrombin type 3; variant confirmed at protein level.
Interchain (between light and heavy chains)
Histone deacetylase complex subunit SAP130
Reduces tail-anchored proteins delivery.
Strongly inhibits interaction with BAG6.
Increased thermal stability of the Pyrin domain.
NACHT, LRR and PYD domains-containing protein 14
Electroneutral sodium bicarbonate exchanger 1
In individuals with NOR polyagglutination syndrome; causes the synthesis of both Gal(alpha1-4)Gal and Gal(alpha1-4)GalNAc moieties.
In p individuals; complete loss of activity.
In p individuals; partial loss of activity.
Lactosylceramide 4-alpha-galactosyltransferase
Golgi-associated RAB2 interactor protein 1B
Abolished alkaline phosphatase activity.
Alkaline phosphatase, tissue-nonspecific isozyme
In HOPS and HPPC; moderate allele; normal alkaline phosphatase activity toward diphosphate and increased activity toward pyridoxal 5'-phosphate.
In HOPS and HPPC; severe allele; abolished alkaline phosphatase activity.
In HOPS; 0.4% of alkaline phosphatase activity; severe allele; no effect on subcellular location; fails to assemble into dimeric structure; dominant negative effect.
In HOPS; 16% alkaline of phosphatase activity.
In HOPS; 30% of alkaline phosphatase activity.
In HOPS; abolished alkaline phosphatase activity.
In HOPS; absence of residual enzymatic activity.
In HOPS; dominant-negative mutant; abolished alkaline phosphatase activity.
In HOPS; in a patient carrying also K-291.
In HOPS; loss of alkaline phosphatase activity.
In HOPS; moderate; 4-10% of alkaline phosphatase activity.
In HOPS; moderate; frequent mutation in European countries; slightly reduced alkaline phosphatase activity.
In HOPS; odonto; abolished alkaline phosphatase activity.
In HOPS; odonto; partial loss of activity.
In HOPS; odonto; slightly reduced alkaline phosphatase activity.
In HOPS; reduced alkaline phosphatase activity toward diphosphate and pyridoxal 5'-phosphate.
In HOPS; reduced alkaline phosphatase toward diphosphate and pyridoxal 5'-phosphate.
In HOPS; reduces alkaline phosphatase activity.
In HOPS; requires 2 nucleotide substitutions.
In HOPS; strongly reduced alkaline phosphatase activity.
In HOPS; unknown pathological significance.
In HOPS; very low alkaline phosphatase activity; does not affect subcellular location.
In HOPS; very low alkaline phosphatase activity; does not affect subcellular location; fails to assemble into dimeric structure.
In HOPS; weak alkaline phosphatase activity.
In HOPS; weak alkaline phosphatase activity; severely affects homodimerization; reduced cell surface expression.
In HPPC and HOPS; severe allele; loss of alkaline phosphatase activity.
In HPPI and HOPS; strongly reduced alkaline phosphatase activity.
In HPPI; does not affect alkaline phosphatase activity.
In MDCMC; decreased choline kinase activity.
In MDCMC; loss of choline kinase activity; decreased amount of phosphatidylcholine in patients cells.
In MDCMC; severely decreased choline kinase activity.
Feline leukemia virus subgroup C receptor-related protein 1
In PCARP; also found in a patient with sensory neuropathy and pain insensitivity.
Probable disease-associated variant found in a patient with sensory neuropathy and pain insensitivity.
Abolished homotetramerization, leading to a homodimer.
Does not affect interaction with NCOR2 and GPS2.
F-box-like/WD repeat-containing protein TBL1X
In CHNG8; unknown pathological significance.
In CHNG8; unknown pathological significance; decreased protein expression.
In CHNG8; unknown pathological significance; no effect on protein expression.
Reduced interaction with NCOR2 and GPS2.
Reduced interaction with NCOR2 and GPS2. Abolished ability to repress transcription.
In PRPS1 superactivity; no effect on Km; resistant to inhibition by ADP and GDP.
Probable disease-associated variant found in a patient with an intermediate phenotype between ARTS and PRPS1 superactivity; normal PRPP synthetase activity in fibroblasts; loss of activity in erythrocytes.
Probable disease-associated variant found in patients with phosphoribosyl pyrophosphate synthetase I deficiency.
Found in a patient with spinocerebellar ataxia; unknown pathological significance.
In ATS2; in isolated microhematuria at heterozygosity.
In ATS2; unknown pathological significance.
In ATS3; in isolated microhematuria at heterozygosity.
S-Lysyl-methionine sulfilimine (Lys-Met) (interchain with M-1533)
S-Lysyl-methionine sulfilimine (Met-Lys) (interchain with K-1651)
Abolished methyltransferase activity in vitro.
Does not affect methyltransferase activity.
Does not affect methyltransferase activity; when associated with A-26.
Does not affect methyltransferase activity; when associated with A-31.
Found in patients with large intestine cancer; abolished methyltransferase activity.
Increased methyltransferase activity in vitro.
RNA N6-adenosine-methyltransferase METTL16
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
FRAS1-related extracellular matrix protein 3
In IDDBCS; unknown pathological significance.
Leukocyte immunoglobulin-like receptor subfamily B member 4
No significant change in APOE-mediated activation of LILRB4.
Significant reduction in APOE-mediated activation of LILRB4.
Reduces the ability to transport carnitine.
Abolished homomultimerization and formation of a CBM complex, abolished ability to activate NF-kappa-B.
Abolished homomultimerization and formation of a CBM complex.
Abolishes NF-kappa-B activation and homo/heterodimerization.
Abolishes cell death-inducing capability.
Complete loss of IKBKB/IKKB-mediated phosphorylation.
Decreased linear ubiquitination and impaired ability to activate NF-kappa-B; when associated with R-31 and R-63.
Decreased ubiquitination and ability to bind NEMO, impaired ability to activate NF-kappa-B; when associated with R-31. Decreased linear ubiquitination and impaired ability to activate NF-kappa-B; when associated with R-17 and R-31.
Decreased ubiquitination and ability to bind NEMO; when associated with 63-R--R-67. Decreased ubiquitination and ability to bind NEMO, impaired ability to activate NF-kappa-B; when associated with R-63. Decreased linear ubiquitination and impaired ability to activate NF-kappa-B; when associated with R-17 and R-63.
Decreased ubiquitination and ability to bind NEMO; when associated with R-31.
Does not affect ubiquitination and ability to bind NEMO.
Found in a MALT lymphoma sample; unknown pathological significance.
Found in a follicular lymphoma sample; unknown pathological significance.
Found in a germ cell tumor and other cancer cell lines; unknown pathological significance.
Found in a germ cell tumor sample; unknown pathological significance.
Found in a mesothelioma sample; unknown pathological significance.
Found in a testicular teratoma sample; somatic mutation.
Sodium-independent sulfate anion transporter
DNA replication complex GINS protein PSF3
May confer susceptibility to obesity; reduces the ability to activate melanocortin receptor 4.
Does not result in CXCL12-inducible chemotaxis, calcium mobilization or ERK activation, and has no effect on CXCR7-mediated CXCL12 degradation; when associated with A-145.
Does not result in CXCL12-inducible chemotaxis, calcium mobilization or ERK activation, and has no effect on CXCR7-mediated CXCL12 degradation; when associated with V-147.
In OCABSN; no effect on protein levels and cell membrane location; lower binding affinity for CXCL12.
In IDDHDF; contrary to the wild-type protein, does not rescue morpholino knockdown phenotype in zebrafish.
Synapse differentiation-inducing gene protein 1
Abolished ability to mediate autocleavage in presence of ssDNA.
Abolished ability to mediate autocleavage. Does not affect DNA-binding.
Abolished ability to mediate autocleavage. Strongly reduced DNA-binding.
Abolished acetylation, leading to impaired localization to chromatin.
Abolished metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs).
Abolished metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs). Abolished ability to cleave CHEK1 during physiological DNA replication.
Abolished metalloprotease activity and ability to mediate autocleavage. Slightly impaired ability to cleave covalent DNA-protein cross-links (DPCs).
Abolished metalloprotease activity, ability to cleave covalent DNA-protein cross-links (DPCs) and to mediate autocleavage.
Abolished phosphorylation by CHEK1; when associated with A-373 and A-374.
Abolished phosphorylation by CHEK1; when associated with A-373 and A-383.
Abolished phosphorylation by CHEK1; when associated with A-374 and A-383.
Abolishes binding to VCP/p97; when associated with A-253.
Abolishes binding to VCP/p97; when associated with A-260.
Does not abolish monoubiquitination; when associated with R-341, R-376 and R-414.
Does not abolish monoubiquitination; when associated with R-341, R-376 and R-435.
Does not abolish monoubiquitination; when associated with R-341, R-414 and R-435.
Does not abolish monoubiquitination; when associated with R-376, R-414 and R-435.
In RJALS; impaired metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs); cells are completely unable to restore DNA replication fork progression.
Increased ability to mediate autocleavage.
Mimics acetylation, promoting cleavage of covalent DNA-protein cross-links (DPCs).
Promotes relocalization to the cytoplasm.
Strongly reduced ability to mediate autocleavage. Strongly reduced DNA-binding.
Abolishes binding to CDE RNA but not dsRNA.
Loss of activity. Loss of MAP3K5 ubiquitination.
Abolishes nuclear localization and phosphorylation by RPS6KB1.
Reduced phosphorylation by RPS6KB1. Abolishes phosphorylation by RPS6KB1; when associated with 21-A-A-22.
Reduced phosphorylation by RPS6KB1. Abolishes phosphorylation by RPS6KB1; when associated with A-7.
In DEE32; affects channel activity; mutant channels display voltage-dependent activation significantly shifted toward negative potentials compared to wild-type; no effect on channel sensitivity to 4-aminopyridine.
In DEE32; dominant-negative mutation; loss of channel function.
Potassium voltage-gated channel subfamily A member 2
Probable disease-associated variant found in a patient with drug-resistant epilepsy.
Abolishes interactions with YWHAB and YWHAZ; when associated with A-834.
Abolishes interactions with YWHAB and YWHAZ; when associated with A-857.
Disintegrin and metalloproteinase domain-containing protein 22
In DEE61; unknown pathological significance; loss of interaction with LGI1; no effect on DLG4-binding, nor on subcellular location.
Ubiquitin-associated domain-containing protein 2
Calmodulin-binding transcription activator 1
Found in patients with late onset progressive myoclonus epilepsy; unknown pathological significance.
Testis-specific serine/threonine-protein kinase 2
In MYOSCO; loss-of-function variant resulting in a reduced muscle stem cell pool; the protein is not detected in patient muscle.
Lethal(2) giant larvae protein homolog 1
Abolished acetylation by KAT5, leading to impaired chromosome segregation.
Leads to loss of kinase activity and severely impairs mitotic progression.
Mimics acetylation, promoting accurate chromosome segregation.
Abolishes glycosylation. Does not affect binding to CDH1, DSC1 or DSG1.
In ARVD12; affects the structure and distribution of mechanical and electrical cell junctions.
In ARVD12; unknown pathological significance.
Loss of ability to stimulate cullin neddylation.
Loss of binding to CAND1 and CUL-RBX1 complex but retains binding to UBE2M.
Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and A-241.Does not affect both nucleus and cytoplasm localization; when associated with A-211 and A-241. Reduces cullin neddylation; when associated with A-211 and A-241. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with A-211 and A-241. Loss of CUL2 interaction; when associated with A-211 and A-241. Reduces neddylation on CUL2; when associated with A-211 and A-241. Reduces interaction with VHL and HIF1A; when associated with A-211 and A-241. Does not affect interaction with SOCS1; when associated with A-211 and A-241. Does not affect DCUN1D1 monoubiquitylation; when associated with A-211 and A-241.
Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and R-235.Does not affect both nucleus and cytoplasm localization; when associated withA-211 and R-235. Reduces cullin neddylation; when associated with A-211 and R-235. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with A-211 and R-235. Loss of CUL2 interaction; when associated with A-211 and R-235. Reduces neddylation on CUL2; when associated with A-211 and R-235. Reduces interaction with VHL and HIF1A; when associated with A-211 and R-235. Does not affect interaction with SOCS1; when associated with A-211 and R-235. Does not affect DCUN1D1 monoubiquitylation; when associated with A-211 and R-235.
Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with R-235 and A-241. Does not affect both nucleus and cytoplasm localization; when associated with R-235 and A-241. Reduces cullin neddylation; when associated with R-235 and A-241. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with R-235 and A-241. Loss of CUL2 interaction; when associated with R-235 and A-241. Reduces neddylation on CUL2; when associated with R-235 and A-241. Reduces interaction with VHL and HIF1A; when associated with R-235 and A-241. Does not affect interaction with SOCS1; when associated with R-235 and A-241. Does not affect DCUN1D1 monoubiquitylation; when associated with R-235 and A-241.
Loss of ubiquitin binding; when associated with A-15, A-16 and A-44.
Loss of ubiquitin binding; when associated with A-15, A-16 and A-45.
Loss of ubiquitin binding; when associated with A-15, A-44 and A-45.
Loss of ubiquitin binding; when associated with A-16, A-44 and A-45.
High affinity immunoglobulin epsilon receptor subunit beta
Risk factor for atopic dermatitis and asthma.
Mediator of RNA polymerase II transcription subunit 9
Loss of function; inhibition of cyclin-B degradation.
Cancer/testis antigen family 45 member A2
Cancer/testis antigen family 45 member A8
Cancer/testis antigen family 45 member A9
In EPM8; expressed and localized properly to the ER; impaired ceramide synthase activity.
In EPM8; unknown pathological significance.
Abolishes formation of 23 and 21 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-127.
Abolishes formation of 28 and 17 kDa cleavage products by CASP3. Abolishes cleavage by caspase-3; when associated with A-157.
Abolishes mitochondrial localization and decreases stability.
Abolishes phosphorylation by MAPK. No effect on phosphorylation induced by okadaic acid or taxol.
Induced myeloid leukemia cell differentiation protein Mcl-1
Loss of phosphorylation by GSK3 and loss of ubiquitination increasing protein stability.
No effect on mitochondrial localization.
In VICIS; relatively mild phenotype characterized by absence or later onset of cardiac or immunologic features; a normally spliced transcript with the missense variant and multiple misspliced transcripts are detected in patient cells; results in 50% decrease of mRNA levels in patient cells most probably due to nonsense-mediated decay of misspliced transcripts.
In VICIS; unknown pathological significance.
In VICIS; unknown pathological significance; associated in cis with P-457.
In VICIS; unknown pathological significance; associated in cis with P-784.
Insulin-like growth factor-binding protein complex acid labile subunit
Associated with coumarin resistance; increased warfarin maintenance dose in patients on warfarin anti-coagulant therapy due to decreased vitamin K catabolism; decreased phylloquinone omega-hydroxylase activity; decreased production of 20-hydroxyeicosatetraenoic acid (20-HETE).
Zinc finger and BTB domain-containing protein 17
In non-Hodgkin lymphoma; somatic mutation.
Loss of BAX-binding and of anti-apoptotic activity.
Loss of BAX-binding and of anti-apoptotic activity. May also affect protein stability.
Loss of BAX-binding and of anti-apoptotic activity. No effect on NLRP1-induced IL1B release, nor on homodimerization. Loss of BAX-binding and of anti-apoptotic activity; when associated with A-145 and A146.
Loss of BAX-binding and of anti-apoptotic activity. No effect on homodimerization.
Loss of BAX-binding and of anti-apoptotic activity; when associated with A-144 and A145.
Loss of BAX-binding and of anti-apoptotic activity; when associated with A-145 and A146.
No effect on BAX-binding, nor on anti-apoptotic activity. Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with L-190 and A-192. No effect on homodimerization; when associated with L-190 and A-191.
Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity.
Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with A-191 and A-192. No effect on homodimerization; when associated with L-190 and A-191.
Partial loss of BAX-binding and 50% decrease in anti-apoptotic activity; when associated with L-190 and A-191. No effect on homodimerization; when associated with L-190 and A-191.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1
B box and SPRY domain-containing protein
Abolished ability to form the NLRP1 inflammasome.
Abolished cleavage by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2.
Abolished formation of an inflammasome filament together with PYCARD/ASC.
Abolished inflammasome filament formation. Impaired ability to induce programmed cell death, but retains CAPS1 processing.
Complete loss of autocatalytic processing and IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine.
Complete loss of autocatalytic processing and of IL1B release.
Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing can be restored by treatment with hydroxylamine.
Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine.
Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. Abolished interaction with DPP9. Loss of activation by dsRNA or positive-strand RNA virus.
Complete loss of autocatalytic processing, which can be restored by treatment with hydroxylamine.
Does not affect ability to induce programmed cell death.
Does not affect formation of an inflammasome filament together with PYCARD/ASC.
Impaired ability to form the NLRP1 inflammasome.
Impaired ability to induce programmed cell death.
Impaired ability to induce programmed cell death. Abolished formation of an inflammasome filament together with PYCARD/ASC.
In 3A mutant; abolished activation of the NLRP1 inflammasome in response to UV-B irradiation and ribosome collisions.
In AIADK; decreased interaction with DPP9, leading to increased inflammasome activity.
In AIADK; unknown pathological significance.
In JRRP; gain-of-function variant resulting in spontaneous inflammasome activation; increased NLRP1-inflammasome complex assembly.
In MSPC; destabilization of the N-terminal fragment.
In MSPC; increased NLRP1-inflammasome complex assembly.
In MSPC; increased NLRP1-inflammasome complex assembly; altered protein folding.
Increased autocatalytic processing and IL1B release.
Inhibits cleavage by HRV-14 Protease 3C.
Inhibits cleavage by Protease 3C from Coxsackievirus B3 and HRV-14.
NACHT, LRR and PYD domains-containing protein 1
NACHT, LRR and PYD domains-containing protein 1, C-terminus
NACHT, LRR and PYD domains-containing protein 1, N-terminus
No effect on autocatalytic processing, nor on IL1B release.
No effect on cleavage by HRV-14 Protease 3C.
Partial loss of autocatalytic processing (50%) and of IL1B release (50%).
Partial loss of autocatalytic processing and of IL1B release.
Phosphothreonine; by MAPK11, MAPK14 and MAP3K20
Reduced autocatalytic processing and reduced interaction with DPP9.
Slightly reduced formation of an inflammasome filament together with PYCARD/ASC.
Decreases current 4-fold in KCNH2/KCNE3 channel.
Found in some patients with periodic paralysis; unknown pathological significance; alters voltage dependence, lowers current and diminishes open probability in KCNC4/KCNE3 channel; lowers current in KCNQ1/KCNE3 channel.
In BRGDA6; also in a patient suffering from drug-induced torsades de pointes; unknown pathological significance.
Potassium voltage-gated channel subfamily E member 3
Dystrophia myotonica WD repeat-containing protein
Decreased interaction with GABARAP and GABARAPL2. Loss of function in TIAM1 ubiquitination and degradation. No effect on assembly of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex.
Kelch repeat and BTB domain-containing protein 6
Loss of interaction with CUL3. Loss of function in TIAM1 ubiquitination and degradation.
In HAE5; decreased oligomerization; decreased interaction with TEK; fails to form proper cell-cell adhesions in an in vitro model of endothelial cell barrier.
In HAE5; unknown pathological significance; does not affect oligomerization; does not affect interaction with TEK.
EF-hand calcium-binding domain-containing protein 7
In PRAAS4; unknown pathological significance.
Abolishes interchain disulfide bond with LTBP1 and/or LRRC32, and subsequent regulation of activation of TGF-beta-1.
Associated with higher bone mineral density and lower frequency of vertebral fractures in Japanese post-menopausal women.
Does not affect integrin-binding or activation of TGF-beta-1.
In CAEND; higher levels of active TGF-beta-1 in the culture medium.
In CAEND; higher levels of active TGF-beta-1 in the culture medium; enhances osteoclast formation in vitro.
In CAEND; leads to TGF-beta-1 intracellular accumulation.
In CAEND; sporadic case; higher levels of active TGF-beta-1 in the culture medium.
In IBDIMDE; decreased TGFB1-mediated activation of SMAD signaling; reduced levels of secreted TGFB1.
In IBDIMDE; loss of TGFB1-mediated activation of SMAD signaling; mutant TGFB1 is not secreted.
Interchain (with C-1359 or C-1384 in LTBP1); in inactive form
Prevents cleavage and subsequent maturation of the protein. Generated in order to mimic the structure of the Transforming growth factor beta-1 proprotein.
Strongly inhibits integrin-binding and activation of TGF-beta-1.
Keeps about 40-50% of prostaglandin-E synthase activity.
Loss of prostaglandin-E synthase activity.
Loss of prostaglandin-E synthase activity. Transforms prostaglandin-E synthase activity to prostaglandin-F(2alpha)synthase activity.
Loss of protaglandin-E synthase activity.
No effect on protaglandin-E synthase activity.
Reduces protaglandin-E synthase activity by 50%.
Reduces protaglandin-E synthase activity by 70%.
Retains 17.8% of protaglandin-E synthase activity.
Retains 21.3% activity of protaglandin-E synthase activity.
Retains partial of protaglandin-E synthase activity.
Slightly reduced protaglandin-E synthase activity.
F-box and WD repeat domain containing protein 10B
In DBQD1 and EDM7; severely affects activity.
In DBQD1; affects protein stability and secretion.
In EDM7; unknown pathological significance.
Increases GDPase activity 2-fold and ADPase activity 5-fold. Forms dimer even at suboptimal Ca(2+) concentrations.
No effect on GDPase and ADPase activities. No effect on dimer formation; when associated with S-287.
Reduces GDPase activity 1.3-fold and ADPase activity 2-fold. Severe loss of dimer formation; when associated with S-287.
Reduces GDPase activity 1.7-fold and ADPase activity 1.5-fold. No effect on dimer formation; when associated with S-287.
Reduces GDPase activity 1.7-fold and ADPase activity 1.5-fold. Severe loss of dimer formation; when associated with S-287.
Reduces GDPase activity 2-fold and ADPase activity 2.5-fold. No effect on dimer formation; when associated with S-287.
Reduces GDPase and ADPase activities 1.3-fold.
Reduces GDPase and ADPase activities 1.7-fold. Severe loss of dimer formation; when associated with S-287.
Soluble calcium-activated nucleotidase 1
tRNA-uridine aminocarboxypropyltransferase 2
Nuclear pore complex-interacting protein family member A7
Nuclear pore complex-interacting protein family member A8
von Willebrand factor C domain-containing protein 2-like
Found in a patient with congenital heart defect.
Probable disease-associated variant found in a patient with congenital heart defect; significant loss of interaction with HDAC1; fails to rescue the abnormal cardiac phenotypes defects in zebrafish morphants.
SET and MYND domain-containing protein 4
Abolishes catalytic activity; abolishes interaction with PARP14.
Protein mono-ADP-ribosyltransferase PARP10
3-hydroxyisobutyryl-CoA hydrolase, mitochondrial
Carbohydrate-responsive element-binding protein
Alkyldihydroxyacetonephosphate synthase, peroxisomal
In RCDP3; does not affect protein levels.
In RCDP3; severely reduced protein levels.
Immunoglobulin superfamily containing leucine-rich repeat protein 2
Protein-glucosylgalactosylhydroxylysine glucosidase
Significantly impairs catalytic activity.
Ribosomal RNA processing protein 36 homolog
Reduces interaction with glycosylated concanavalin-A in vitro.
AT-rich interactive domain-containing protein 3B
Striated muscle preferentially expressed protein kinase
WD repeat- and FYVE domain-containing protein 4
Mitochondrial import inner membrane translocase subunit Tim21
Acyl-coenzyme A synthetase ACSM5, mitochondrial
Alters interaction with REV3L and REV1. Loss of interaction with REV3L; when associated with A-63. No effect on interaction with REV1; when associated with A-124.
Alters interaction with REV3L. Loss of interaction with REV3L; when associated with A-171.
In FANCV; drastically reduced protein abundance.
Induces structural changes that increase affinity for REV3L and REV1. No effect on interaction with REV1; when associated with A-171.
Mitotic spindle assembly checkpoint protein MAD2B
Significantly prevents interaction with REV1; no effect on interaction with REV3L.
PIK3R3 upstream open reading frame protein
About 10-fold increase in interferon beta production.
Heterogeneous nuclear ribonucleoproteins A2/B1
Cell surface glycoprotein CD200 receptor 2
Cyclin N-terminal domain-containing protein 1
Loss of catalytic activity. No effect on bactericidal activity.
Moderate loss of bactericidal activity. No effect on catalytic activity.
No significant effect on bactericidal activity or catalytic activity.
Significant loss of bactericidal activity. No effect on catalytic activity.
Slight loss of bactericidal activity. No effect on catalytic activity.
Abolishes interaction with INSC; when associated with E-228.
Abolishes location at mitotic spindle poles; when associated with A-228.
Abolishes location at mitotic spindle poles; when associated with A-243.
Strongly reduces interaction with INSC. Abolishes interaction with INSC; when associated with R-290.
Putative transcription factor Ovo-like 1
Killer cell immunoglobulin-like receptor 2DS4
Abolishes cleavage of the first 13 residues.
Inverts transmembrane topology. Induces cleavage of CREB3L1.
No effect on cleavage of the first 13 residues.
No effect on glycosylation upon ceramide treatment.
Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-148.
Reduces glycosylation upon ceramide treatment. Abolishes glycosylation upon ceramide treatment; when associated with Q-132 and Q-163.
Cytosolic 10-formyltetrahydrofolate dehydrogenase
Loss of phosphopantetheinylation by AASDHPPT. Loss of formyltetrahydrofolate dehydrogenase activity.
Can be associated with insulin resistance.
Protein phosphatase 1 regulatory subunit 3A
Found in a patient with spastic paraplegia; unknown pathological significance.
Impairs deubiquitination activity and leads to endosome membrane accumulation.
In PITA4; somatic mutation; unknown pathological significance.
In PITA4; somatic mutation; unknown pathological significance; localizes to nucleus instead of cytoplasm.
ADP-ribosylation factor-like protein 13B
Abolishes sumoylation. Abolishes sumoylation; when associated with R-231; R-270; R-275; R-276 and R-279.
In JBTS8; the patient also manifests obesity as a feature; decreased localization to cilium.
No effect. Abolishes sumoylation; when associated with R-231; R-270; R-275; R-276 and R-329.
No effect. Abolishes sumoylation; when associated with R-231; R-270; R-275; R-279 and R-329.
No effect. Abolishes sumoylation; when associated with R-231; R-270; R-276; R-279 and R-329.
No effect. Abolishes sumoylation; when associated with R-231; R-275; R-276; R-279 and R-329.
No effect. Abolishes sumoylation; when associated with R-270; R-275; R-276; R-279 and R-329.
Accumulation in the nucleus due to defects in nuclear export.
Impaired phosphorylation, inducing accumulation in the nucleus.
Loss of RPA1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with A-499 and A-506.
Loss of RPA1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with A-499 and A-510.
Loss of RPA1-binding, leading to impaired recruitment to sites of double-strand breaks; when associated with A-506 and A-510.
Phosphomimetic mutant; leads to higher localization to the cytoplasm.
Mini-chromosome maintenance complex-binding protein
Fibronectin type III domain-containing protein 11
In NS11; constitutively active form; increased GTPase activity.
snRNA-activating protein complex subunit 1
In CMS14; shows severely reduced expression of the mutant protein.
Endothelial zinc finger protein induced by tumor necrosis factor alpha
Found in a patient with autism spectrum disorder; unknown pathological significance; induces response to endoplasmic reticulum stress; negative regulation of dendrite morphogenesis.
Abolishes enzyme activity. Reduces lipid droplet formation; when associated with A-54; A-385 and A-402.
Abolishes enzyme activity. Reduces lipid droplet formation; when associated with A-54; A-82 and A-385.
Abolishes enzyme activity. Reduces lipid droplet formation; when associated with A-54; A-82 and A-402.
Abolishes enzyme activity. Reduces lipid droplet formation; when associated with A-82; A-385 and A-402.
Has no effect on membrane localization. Decreases the affinity for 1-O-hexadecyl-sn-glycero-3-phosphocholine acyl acceptor in transacylation reaction.
Myosin phosphatase Rho-interacting protein
Heterogeneous nuclear ribonucleoprotein C-like 3
Heterogeneous nuclear ribonucleoprotein C-like 4
Associated with SHEP4; greatly reduced exchange activity.
In TPID; no effect on triose-phosphate isomerase activity; changed protein homodimerization activity; the homodimer stability is temperature-dependent and affects the triose-phosphate isomerase activity.
In LS; unknown pathological significance; decrease in enzyme activity.
Associated in cis with S-2787; may be associated with susceptibility to malignant hyperthermia.
Associated in cis with W-2676; may be associated with susceptibility to malignant hyperthermia.
In CCD and MHS1; 2-3% of the cases; increases calcium-induced calcium release activity.
In CCD and MHS1; 3-5% of the cases; increases calcium-induced calcium release activity.
In CCD and MHS1; increases calcium-induced calcium release activity.
In CCD and MHS1; no difference in the thapsigargin-sensitive calcium stores of cells carrying this mutation and the wild-type; increases calcium-induced calcium release activity.
In CCD and MHS1; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR.
In CCD; increases sensitivity to caffeine and 4-chloro-m-cresol.
In CCD; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR; smaller thapsigargin-sensitive intracellular calcium stores; normal sensitivity of the calcium release to the RYR inhibitor dantrolene.
In CCD; unknown pathological significance.
In KDS; unknown pathological significance.
In MHS1 and CCD; autosomal recessive form.
In MHS1, CCD and KDS; increases sensitivity to caffeine and 4-chloro-m-cresol; increases calcium-induced calcium release activity.
In MHS1; 10% of the cases; increases calcium-induced calcium release activity.
In MHS1; has increased sensitivity to both caffeine and halothane.
In MHS1; increases calcium-induced calcium release activity.
In MHS1; increases sensitivity to caffeine and 4-chloro-m-cresol; increases calcium-induced calcium release activity.
In MHS1; induces an increase sensitivity to caffeine.
In MHS1; induces an increase sensitivity to caffeine; increases calcium-induced calcium release activity.
In MHS1; requires 2 nucleotide substitutions; unknown pathological significance.
In MHS1; reveals an altered calcium dependence and increased caffeine sensitivity; increases calcium-induced calcium release activity.
In MHS1; severe form; increases calcium-induced calcium release activity.
In MHS1; unknown pathological significance.
In MHS1; unknown pathological significance; increases calcium-induced calcium release activity.
In MHS1; unknown pathological significance; slightly increases Ca(2+) release in response to 4-chloro-m-cresol.
In MMDO and CCD; autosomal recessive form.
Increases calcium-induced calcium release activity.
Increases sensitivity to caffeine and 4-chloro-m-cresol.
May be associated with susceptibility to malignant hyperthermia.
Probable disease-associated variant found in a family with Samaritan myopathy.
Probable disease-associated variant found in primary myopathy causing fetal akinesia and pregnancy loss.
Abolishes interaction with CPSF6; when associated with A-158.
Abolishes interaction with CPSF6; when associated with A-160.
Cleavage and polyadenylation specificity factor subunit 5
Reduces affinity for UGUA RNA by over 90%.
Reduces interactions with CPSF6 and CPSF7 and decreases mRNA 3'-processing activity.
Binds calcium but with decreased affinity.
In APRTD; Japanese type; allele APRT*J; most common mutation.
In MLASA2; has a 2-fold reduction in catalytic activity and a reduction in affinity for tRNA-tyr resulting in an overall 9-fold loss of catalytic efficiency.
Increased pro-apoptotic activity; when associated with D-56.
Increased pro-apoptotic activity; when associated with D-96.
Interferon alpha-inducible protein 27, mitochondrial
COX assembly mitochondrial protein homolog
5'-AMP-activated protein kinase catalytic subunit alpha-1
Coiled-coil domain-containing protein 192
In MC1DN28; reduced NDUFA13 protein level resulting in complex I instability.
In a Hurthle cell variant of papillary carcinoma sample.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13
In isoform Alpha-2, isoform Beta-2 and isoform 7.
Low-density lipoprotein receptor class A domain-containing protein 4
Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial
Found in a patient with gout; does not affect isoform 2 localization at the cell membrane; results in reduced urate efflux.
Found in a patient with hyperuricemia; decreased expression of isoform 2 at the cell membrane; results in highly reduced urate efflux.
Sodium-dependent phosphate transport protein 4
In HYXKY; reduced 3-hydroxykynureninase activity.
In VCRL2; strongly reduced 3-hydroxykynureninase activity.
The reported mass is given to only three significant figures.
Haloacid dehalogenase-like hydrolase domain-containing protein 2
Ras association domain-containing protein 9
Abolishes interaction with GFRAL. Abolishes RET phosphorylation and cellular signaling mediated by GFRAL and RET.
No effect on interaction with GFRAL. Attenuates GDF15-mediated food-intake inhibition.
Reduces cellular signaling mediated by GFRAL and RET.
Reduces cellular signaling mediated by GFRAL and RET. Abolishes interaction with GFRAL and GDF15-mediated food-intake inhibition.
In DCBXA; inhibits L-glutamate and L-cysteine transport activities.
In DCBXA; reduces L-glutamate and L-cysteine transport activities; reduces cell membrane expression.
Transforming growth factor-beta receptor-associated protein 1
Coiled-coil domain-containing protein 83
U3 small nucleolar RNA-associated protein 6 homolog
Plasma membrane calcium-transporting ATPase 1
Lymphocyte antigen 6 complex locus protein G6f
No phosphorylation. No interaction with GRB2 and GRB7. No phosphorylation increase of p42/44 MAP kinase.
Intraflagellar transport protein 46 homolog
Glucose-induced degradation protein 8 homolog
WAP four-disulfide core domain protein 3
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase
Decreased activity as transcriptional repressor.
No effect on activity as transcriptional repressor.
Slightly decreased activity as transcriptional repressor.
Slightly increased activity as transcriptional repressor. Lack of catalytic activity.
Loss of CDK1-mediated phosphorylation. Abolishes targeting onto the mitotic spindle; when associated with A-60.
Loss of CDK1-mediated phosphorylation. Abolishes targeting onto the mitotic spindle; when associated with A-712.
In CSS8; unknown pathological significance.
Loss of demethylase activity. Defective in the binding of FAD.
Strongly reduced demethylase activity. Loss of enzymatic activity; when associated with 273-G--S-278.
Strongly reduced demethylase activity. Loss of enzymatic activity; when associated with 285-A--A-287.
CUB and sushi domain-containing protein 2
Loss of transactivation activity in response to IFNG.
N6-acetyllysine; by KAT2A and KAT2B; alternate
Phosphothreonine; by RPS6KA1 and PKC/PRKCA
Phosphothreonine; by RPS6KA1, CDK2 and MAPK
Decreases LDL, CLU and APOE binding; decreases LDL and CLU uptake into cells; no effect on cell membrane localization.
Does not affect protein structure; no effect on cell membrane localization; increases autophagy in microglia; decreases LDL, CLU and APOE binding; decreases LDL uptake into cells; no effect on CLU uptake into cells; decreases the uptake of APP-LDL complex in macrophages; decreases binding to oligomeric APP cleavage product beta-amyloid peptide 42.
Does not change protein structure; changes protein stability; increases binding to THP-1 cells.
Found in patients with Alzheimer disease; unknown pathological significance; decreases cell membrane localization.
Found in patients with Alzheimer disease; unknown pathological significance; slightly decreases cell membrane localization.
Found in patients with late onset Alzheimer disease; unknown pathological significance; decreases cell membrane localization.
Found in patients with late onset Alzheimer disease; unknown pathological significance; increases cell membrane localization.
Found in patients with late onset Alzheimer disease; unknown pathological significance; no effect on cell membrane localization.
Found in patients with late onset Alzheimer disease; unknown pathological significance; no effect on cell membrane localization; no effect on autophagy in microglia; no effect on phagocystosis, including amyloid plaque clearance by microglia; reduces ectodomain shedding caused by proteolytic cleavage by ADAM10, while also reducing the oligomerization of the extracellular domain after shedding; decreases binding to and uptake of LDL and CLU into cells; decreases binding to APOE, phospholipids and oligomeric APP cleavage product beta-amyloid peptide 42.
In PLOSL2; no protein detected by Wester blot.
In PLOSL2; results in decreased osteoclast differentiation; no TREM2 transcripts can be detected in patient cells homozygous for the variant.
In PLOSL2; results in defective protein maturation; increases protein aggregation; decreases cell membrane localization.
In PLOSL2; unknown pathological significance; decreased protein level.
In PLOSL2; unknown pathological significance; increased localization at the cell membrane.
Likely benign variant; no effect on protein expression and maturation.
Loss of proteolytic cleavage by ADAM10 and ectodomain shedding. Decreases protein maturation and cell membrane localization.
May be associated with an increased risk for late-onset Alzheimer disease; accelerates ectodomain shedding but does not alter the cleavage site; decreases cell membrane localization; decreases phagocytosis.
No effect on cell membrane localization.
No effect on protein expression and maturation.
Results in defective protein maturation and trafficking; loss of proteolytic cleavage by ADAM10 and ectodomain shedding; increases protein aggregation; decreases cell membrane localization; decreased phagocytosis; loss of LDL, CLU and APOE binding; greatly decreases LDL and CLU uptake into cells.
Results in defective protein maturation and trafficking; loss of proteolytic cleavage by ADAM10 and ectodomain shedding; increases protein aggregation; decreases cell membrane localization; decreases phagocytosis; loss of LDL, CLU and APOE binding; greatly decreases LDL and CLU uptake into cells.
Triggering receptor expressed on myeloid cells 2
Neuroblastoma breakpoint family member 3
Abolishes kinase activity. Abolishes location at microtubules.
In an ovarian Endometrioid carcinoma sample; somatic mutation.
In CDAN2; the mutant protein is unstable with less than 5% of protein detectable compared to wild-type.
In CDAN2; unknown pathological significance.
In CDAN2; unknown pathological significance; the mutant protein is expressed as the wild-type.
In CWS7; aberrant aggregation; causes mislocalization of the protein in the cytoplasm; reduces interaction with SAR1A; confers endoplasmic reticulum (ER) stress-mediated cell growth advantage.
In CWS7; unknown pathological significance.
In allele CYP2C19*16; lowered catalytic activity.
In allele CYP2C19*1B, allele CYP2C19*1C, allele CYP2C19*2A, allele CYP2C19*2B, allele CYP2C19*2C, allele CYP2C19*2E, allele CYP2C19*2F, allele CYP2C19*2G, allele CYP2C19*2H, allele CYP2C19*2J, allele CYP2C19*3A, allele CYP2C19*3B, allele CYP2C19*3C, allele CYP2C19*4A, allele CYP2C19*4B, allele CYP2C19*6, allele CYP2C19*9, allele CYP2C19*10, allele CYP2C19*11, allele CYP2C19*12, allele CYP2C19*13, allele CYP2C19*14, allele CYP2C19*15, allele CYP2C19*18, allele CYP2C19*19, allele CYP2C19*22, allele CYP2C19*23, allele CYP2C19*24, allele CYP2C19*25, allele CYP2C19*26, allele CYP2C19*27, allele CYP2C19*28, allele CYP2C19*29, allele CYP2C19*31, allele CYP2C19*32, allele CYP2C19*33 and allele CYP2C19*35.
In allele CYP2C19*5A and allele CYP2C19*5B; loss of activity.
Found in patients with autism spectrum disorders; unknown pathological significance.
In MRXST; decreased protein levels in patient cells.
In MRXST; increased protein levels in patient cells.
In CSID; SI accumulates predominantly in the ER.
In CSID; causes loss of anchored SI from the membrane.
In CSID; exhibits intracellular accumulation of mannose-rich SI in the Golgi.
In CSID; missorting of the enzyme to the basolateral membrane.
In isoform PACE4A-II and isoform PACE4E-II.
In isoform PACE4E-I and isoform PACE4E-II.
Proprotein convertase subtilisin/kexin type 6
Complete loss of GABA transporter activity.
Found in a patient with generalized epilepsy; unknown pathological significance; complete loss of GABA transporter activity.
Found in a patient with generalized epilepsy; unknown pathological significance; retains about 6% of wild-type GABA transporter activity.
Found in a patient with intractable absence epilepsy; unknown pathological significance; retains about 27% of wild-type GABA transporter activity.
In MAE; unknown pathological significance; retains about 13% of wild-type GABA transporter activity.
In MAE; unknown pathological significance; retains about 2% of wild-type GABA transporter activity.
Sodium- and chloride-dependent GABA transporter 1
Eukaryotic translation initiation factor 4 gamma 2
In NECRC; does not localize to the nucleus; decreased interaction with FOXP1 and FOXP2.
In NECRC; does not localize to the nucleus; loss of interaction with FOXP1 and FOXP2.
Likely benign variant; found in a patient with congenital anomalies of the kidney and urinary tract; no effect on localization to the nucleus.
Likely benign variant; found in a patient with congenital anomalies of the kidney and urinary tract; no effect on localization to the nucleus; no effect on transcriptional repression activity.
Likely benign variant; found in a patient with congenital anomalies of the kidney and urinary tract; requires 2 nucleotide substitutions; no effect on localization to the nucleus.
Pleckstrin homology domain-containing family H member 2
Loss of GTPase activity. Does not inhibit filopodia formation.
Loss of phosphorylation. No effect on GDI1 and GDI2 binding.
Phosphomimetic mutant. Loss of GDI1 and GDI2 binding.
Strongly decreases RABEP1 and ZFYVE20 binding affinity.
Strongly decreases RABEP1 binding affinity.
Strongly decreases RABEP1 binding affinity. Impairs endosome fusion.
Strongly decreases ZFYVE20 binding affinity.
Decreases levels of sulfotransferase activity.
Decreases levels of sulfotransferase activity; accelerates proteasome-dependent degradation.
Decrease in catalytic activity by about 10-fold.
Decrease in catalytic activity by more than 10-fold.
Displays 62% of wild-type catalytic activity. Displays 20% of wild-type catalytic activity; when associated with G-125.
Found in a patient with mild left ventricular posterior wall hypertrophy, exercise intolerance and lactic acidosis; unknown pathological significance.
Has no effect on subcellular localization; results in decreased affinity for glycine.
In CMT2D and HMN5A; shows a large reduction in aminoacylation activity.
In CMT2D and HMN5A; shows a large reduction in aminoacylation activity; demonstrates a change in the subcellular location pattern; does not associate with granules.
In CMT2D; demonstrates no change in subcellular location pattern.
In CMT2D; phenotype overlapping with HMN5A; complements the defect of the wild-type gene in yeast; contrary to the wild-type protein, strongly binds to NRP1 and competes with VEGFA for NRP1-binding; displays slightly elevated aminoacylation activity over wild-type.
In CMT2D; shows a large reduction in aminoacylation activity; demonstrates a change in subcellular location pattern; does not associate with granules.
In CMT2D; shows a large reduction in aminoacylation activity; demonstrates a change in subcellular location pattern; does not associate with granules; unknown pathological significance.
In CMT2D; shows a large reduction in aminoacylation activity; does not impair transcription or translation or protein stability; contrary to the wild-type protein, strongly interacts with NRP1.
In CMT2D; shows a reduction in aminoacylation activity.
In CMT2D; unknown pathological significance.
In HMN5A; does not complement the defect of the wild-type gene in yeast; contrary to the wild-type protein, strongly interacts with NRP1.
In HMN5A; higher dimerization stability; loss of activity; shows a large reduction in aminoacylation activity.
In HMN5A; shows a large reduction in aminoacylation activity; does not complement the defect of the wild-type gene in yeast.
In HMN5A; unknown pathological significance.
In SMAJI; loss of function; based on yeast complementation assay.
Probable disease-associated variant found in a patient with growth retardation, microcephaly, thinning of the corpus callosum, decreased white matter and brain stem involvement, as well as large calvaria, cerebellar vermis atrophy, dysmorphic features, prominent epicanthal folds, hypotelorism, high-arched palate, delayed motor milestones, apnea and sparse thin scalp hair; reduces to less than 1% aminoacylation activity.
Decreased interaction with AP2A2; when associated with A-369.
Decreased interaction with AP2A2; when associated with A-372.
Altered regulation of oligomerization by phosphorylation at S-222.
Loss of regulation of oligomerization by phosphorylation at S-222.
Diffused nuclear localization, loss of nucleolar localization.
Loss of GTP-binding. Efficient localization to the nucleus, but excluded from nucleoli.
Loss of GTP-binding. Punctate pattern throughout the nucleus, including nucleoli.
No effect on GTP-binding, nor on nucleolar localization.
No effect on nucleolar localization Predominantly cytoplasmic, with some nucleolar staining; when associated with 682-AAA-684. Strong nucleolar localization, with some cytoplasmic staining; when associated with 724-AAA-726. Diffused localization to both cytoplasm and nucleus; when associated with 682-AAA-684 and 724-AAA-726.
No effect on nucleolar localization. Predominantly cytoplasmic, with some nucleolar staining; when associated with 711-AAA-713. Diffused localization to both cytoplasm and nucleus; when associated with 711-AAA-713 and 724-AAA-726.
No effect on nucleolar localization. Strong nucleolar localization, with some cytoplasmic staining; when associated with 711-AAA-713. Diffused localization to both cytoplasm and nucleus; when associated with 682-AAA-684 and 711-AAA-713.
No effect on nucleolar localization; when associated with A-463.
No effect on nucleolar localization; when associated with A-475.
Abolishes self-interaction and interaction with HSPA9 and the CIA complex but does not alter subcellular localization; when associated with S-41; S-44 and S-58.
Abolishes self-interaction and interaction with HSPA9 and the CIA complex but does not alter subcellular localization; when associated with S-41; S-44 and S-61.
Abolishes self-interaction and interaction with HSPA9 and the CIA complex but does not alter subcellular localization; when associated with S-41; S-58 and S-61.
Abolishes self-interaction and interaction with HSPA9 and the CIA complex but does not alter subcellular localization; when associated with S-44; S-58 and S-61.
Does not interact with HSPA9. Does not inhibit interaction with ISCU.
Iron-sulfur cluster co-chaperone protein HscB, cytoplasmic
Iron-sulfur cluster co-chaperone protein HscB, mitochondrial
Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-74.
Loss of autophosphorylation and of kinase activity and induction of apoptosis; when associated with M-75.
Impaired import of NAD(+) into mitochondria.
Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51
In PFIC7; unknown pathological significance.
Inactive ubiquitin carboxyl-terminal hydrolase 53
Complete loss of phosphatidylinositol transfer activity but no effect on phosphatidylcholine transfer activity.
No effect on phosphatidylinositol transfer activity.
No effect on phosphatidylinositol transfer activity. Resistant to inhibition by N-ethylmaleimide.
Phosphatidylinositol transfer protein alpha isoform
Reduced phosphatidylinositol and phosphatidylcholine transfer activity.
Reduced phosphatidylinositol transfer activity but no effect on phosphatidylcholine transfer activity.
Significant loss of phosphatidylinositol and phosphatidylcholine transfer activity.
Significant loss of phosphatidylinositol transfer activity but no effect on phosphatidylcholine transfer activity.
ATP synthase subunit epsilon, mitochondrial
Phosphotyrosine; by autocatalysis, LYN and JAK2
Coiled-coil domain-containing protein 183
Abolishes interaction with IRS1 and SHC1.
Abolishes interaction with IRS1 and significantly reduces interaction with SHC1. Has no effect on interaction with PIK3R1.
Abolishes interaction with IRS1. Severely disrupts, but does not abolish interaction with SHC1.
Abolishes the kinase activity and abolishes interaction with IRS1, SHC1, GRB7 and PIK3R1.
Does not affect interaction with IRS1, SHC1 or PIK3R1.
Has no effect on insulin-stimulated autophosphorylation, but inhibits the biological activity of the receptor. Abolishes interaction with IRS1 and almost completely prevents interaction with SHC1. Has no effect on interaction with PIK3R1. Abolishes interaction with STAT5B.
In HHF5 and IRAN type A; interferes with kinase activation by insulin.
In IRAN type A; accelerates degradation of the protein and impairs kinase activity.
In IRAN type A; impairs proteolytic processing.
In IRAN type A; inhibits receptor internalization.
In IRAN type A; interferes with receptor processing.
In IRAN type A; unknown pathological significance.
In LEPRCH and RMS; reduces insulin binding possibly due to reduced receptor levels on the cell surface.
In LEPRCH; Atlanta-1; abolishes insulin binding.
In LEPRCH; Helmond; inhibits processing and transport.
In LEPRCH; abolishes post-translational processing.
In LEPRCH; abolishes post-translational processing; abolishes insulin binding.
In LEPRCH; impaired receptor processing; impairs post-translational processing.
In LEPRCH; impairs post-translational processing.
In LEPRCH; impairs transport of the receptor to the cell surface.
In LEPRCH; inhibits receptor processing.
In LEPRCH; markedly impairs insulin binding.
In LEPRCH; markedly impairs insulin binding;impairs post-translational processing.
In LEPRCH; partially inhibits receptor processing and autophosphorylation; strongly impairs ERK phosphorylation; induces wild-type levels of IRS-1 phosphorylation.
In RMS and LEPRCH; Winnipeg; may impair receptor processing.
In RMS; decreases post-translational processing.
In RMS; impairs post-translational processing.
In RMS; impairs transport to the plasma membrane and reduces the affinity to bind insulin.
Reduces interaction with IRS1 but has no effect on interaction with SHC1.
Severely reduces interaction with SHC1. Has no effect on interaction with IRS1.
Decreasing protein levels. Loss of enzymatic activity.
Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability.
Does not affect isomerohydrolase activity.
In LCA2 and RP20; severely decreased retinol isomerase activity.
In LCA2; benign variant; no effect on retinol isomerase activity.
In LCA2; reduced protein levels; decreased function in the retinoid cycle.
In LCA2; severely decreased retinol isomerase activity.
In LCA2; unknown pathological significance.
In RP20 and LCA2; reduced protein levels; decreased function in the retinoid cycle.
In RP20; likely benign variant; very mild decrease of retinol isomerase activity.
In RP20; uncertain pathological significance.
In RP20; unknown pathological significance.
In RP87; unknown pathological significance; does not affect protein abundance; does not affect subcellular localization; does not affect isomerization activity; may cause abnormal splicing mRNAs thereby decreasing protein levels.
Loss of enzymatic activity. No palmitoylation. Loss of membrane association.
No effect on retinol isomerase activity.
No loss of enzymatic activity. No effect on palmitoylation. No loss of membrane association.
Modest changes in KM for ATP. 100-fold increase in KM for mevalonate. Approximately 2-fold increase in Vmax.
Modest changes in KM for ATP. 20-fold increase in KM for mevalonate. 4000-fold decrease in Vmax.
Modest changes in KM for ATP. 20-fold increase in KM for mevalonate. Approximately 2-fold decrease in Vmax.
Modest changes in KM for ATP. 40-fold increase in KM for mevalonate. Approximately 2-fold decrease in Vmax.
No change in protein stability. Decreased kinase activity. Approximately 50-fold decrease in Vmax. Approximately 20- and 40-fold decrease affinities for ATP and mevalonate, respectively.
No change in protein stability. Loss of kinase activity. Normal affinities for ATP and mevalonate.
No change in protein stability. No effect on kinase activity.
No change in protein stability. Weak decrease in kinase activity. Approximately 2-fold decrease in Vmax. Approximately 2-fold decrease affinity for ATP and mevalonate.
No effect on kinase activity. Approximately 2- and 3-fold decrease affinities for ATP and mevalonate, respectively.
No effect on kinase activity. Approximately 4- and 5-fold decrease affinities for ATP and mevalonate, respectively.
No effect on kinase activity. Approximately 4- and 8-fold decrease affinities for ATP and mevalonate, respectively.
No effect on kinase activity. Approximately 4-fold increase affinity for ATP. Normal affinity for mevalonate.
No effect on interactions with CUL2 and HIF1A.
Severely reduces interaction with neddylated CUL2.
Abolishes interaction with microcystin toxin.
Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 2
In IEHDCM; reduced folding stability as measured by differential scanning calorimetry of the mutant protein; impairs interaction with FAS.
Loss of interaction with CASP8. Abolishes induction of apoptosis. Decreased interaction with FAS.
Loss of interaction with FAS. Loss of self-association. Abolishes induction of apoptosis.
Strongly decreased interaction with FAS.
Abolishes enzyme activity but not phosphorylation upon FCGR2A clustering.
Abolishes interaction with p130Cas/BCAR1 and its ability to induce increased adhesion. Abolishes phosphorylation upon FCGR2A clustering.
Associated with susceptibility to NIDDM.
Inducer a strong reduction of phosphorylation upon re-plating on collagen I.
Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2
Reduces PDGF-stimulated tyrosine phosphorylation and association with SHC1.
Increased binding to GRB2 and enhanced cell proliferation.
Loss of heterochromatin association during interphase and loss of chromatin association during anaphase.
Loss of heterochromatin association. Loss of interaction with CBX5.
Dipeptidyl peptidase 1 exclusion domain chain
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9
Transcriptional activator protein Pur-alpha
Abolishes interaction with CTNNB1; when associated with A-366.
Abolishes interaction with CTNNB1; when associated with A-369.
Impairs plus end-directed microtubule-dependent motor activity, leading to impair EGFR recycling.
Induces a 3-fold decrease in PtdIns(3)P-binding; when associated with A-1225 and A-1229.
Induces a 3-fold decrease in PtdIns(3)P-binding; when associated with A-1225 and A-1232.
Induces a 3-fold decrease in PtdIns(3)P-binding; when associated with A-1229 and A-1232.
Induces a 30-fold decrease in PtdIns(3)P-binding.
Induces a 5-fold decrease in PtdIns(3)P-binding and abolishes endosome localization. Induces a 25-fold decrease in PtdIns(3)P-binding; when associated with A-1248.
Induces a 6-fold decrease in PtdIns(3)P-binding.
Induces a 7-fold decrease in PtdIns(3)P-binding and abolishes endosome localization. Induces a 25-fold decrease in PtdIns(3)P-binding; when associated with A-1249.
Reduces copper-induced fluorescence change.
Almost complete loss of activity. Reduces membrane localization.
In LIKNS; causes reduced expression of the mutant protein; hypoglycosylated; does not localize properly at the plasma membrane; small residual activity.
In LIKNS; unknown pathological significance.
Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane.
Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane. Abolishes interaction with TESC.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-518.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-522.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-526.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-527.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-530.
Reduces interaction with CHP1 and the exchange activity; when associated with Q-531.
Lipopolysaccharide-responsive and beige-like anchor protein
Glutamate-rich WD repeat-containing protein 1
In isoform 13, isoform 14, isoform 15 and isoform 16.
In isoform 2, isoform 3, isoform 6, isoform 7, isoform 10, isoform 12, isoform 13 and isoform 14.
In isoform 2, isoform 4, isoform 5, isoform 7, isoform 9, isoform 10, isoform 13, isoform 15 and isoform 16.
In isoform 3, isoform 4, isoform 7, isoform 8, isoform 13, isoform 14 and isoform 16.
In isoform 5, isoform 11, isoform 10 and isoform 12.
Loss of membrane dissociation and binding to YWHAZ.
In IGHD5; impairs binding to U12 and U6atac small nuclear RNAs; leads to a partial defect in the folding of RRM 2 domain and reduced stability of the full-length protein.
In IGHD5; reduced expression due to nonsense-mediated mRNA decay; impairs binding to U12 and U6atac small nuclear RNAs.
Glutamate--cysteine ligase regulatory subunit
Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole
In EDSPD1; requires 2 nucleotide substitutions; the mutant is not secreted but retained intracellularly.
In EDSPD1; the mutant is not secreted but retained intracellularly.
In EDSPD1; unknown pathological significance.
Abolishes interaction with membranes enriched in phosphatidylinositol 3-phosphate.
In CGD3; the protein remains cytosolic, does not localize to phagosomes or endosomes and is unable to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) in a lipid-binding assay; unable to rescue the NADPH-oxidase defect of NCF4 functionally null cells.
Slightly reduces interaction with membranes enriched in phosphatidylinositol 3-phosphate.
Strongly reduces interaction with membranes enriched in phosphatidylinositol 3-phosphate.
In BRGDA9; unknown pathological significance; does not affect the electrophysiological properties of the channel.
In BRGDA9; unknown pathological significance; gain of function mutation.
In SCA19; results in reduced channel activity consistent with impaired cell surface expression of the mutant protein.
In SCA19; unknown pathological significance; causes reduced channel activity.
In SCA19; unknown pathological significance; results in impaired cell surface expression.
Potassium voltage-gated channel subfamily D member 3
Zinc finger and BTB domain-containing protein 37
Abolishes phosphorylation and reduces strongly nuclear localization.
Does not abolish nuclear localization and reduces DNA-binding ability.
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4
N-terminal EF-hand calcium-binding protein 1
Pre-B-cell leukemia transcription factor-interacting protein 1
Inactivates CRM1 binding; when associated with R-300.
Inactivates CRM1 binding; when associated with R-302.
Glial cell line-derived neurotrophic factor
In HSCR3; unknown pathological significance.
May be a risk factor for Hirschsprung disease.
ATP-binding cassette sub-family C member 10
Almost complete loss of tRNA ligase activity.
Disrupts interaction with AIMP2 and the multisynthase complex.
Disrupts interaction with AIMP2 and the multisynthase complex. Increases production of diadenosine tetraphosphate (Ap4A). Almost complete loss of tRNA ligase activity.
Found in a patient with hypertrophic cardiomyopathy and mild intellectual disability together with proximal muscle weakness; unknown pathological significance.
In CMTRIB; severely affects enzyme activity.
In DEAPLE and LEPID; decreases tRNA-lysine aminoacylation; induces protein aggregation; releases from the subunit complex; no effect on cytoplasmic location; no effect on oligomerization.
In DEAPLE and LEPID; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation.
In DEAPLE; decreases tRNA-lysine aminoacylation; slightly induces protein aggregation; no effect on cytoplasmic location; no effect on oligomerization.
In DEAPLE; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation.
In DEAPLE; unknown pathological significance.
In LEPID; decreases tRNA-lysine aminoacylation activity of both the mitochondrial and cytosolic forms. Does not rescue the developmental defects caused by KARS1 depletion in xenopus.
In LEPID; does not rescue the developmental defects caused by KARS1 depletion in xenopus.
In LEPID; unknown pathological significance.
Induces protein aggregation. Releases from the subunit complex.
Loss of nuclear localization, but no effect on packaging into HIV-1.
Phosphomimetic mutant that strongly enhances translocation into the nucleus and production of diadenosine tetraphosphate (Ap4A). Almost complete loss of tRNA ligase activity.
Strongly decreased tRNA ligase activity.
Strongly reduced production of diadenosine tetraphosphate (Ap4A). Reduced protein phosphorylation.
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit
tRNA N(3)-methylcytidine methyltransferase METTL2B
Reduces catalytic activity towards inosine, hypoxanthine, guanosine and guanine. Increases catalytic activity towards adenosine and adenine.
Reduces catalytic activity towards inosine.
Impairs binding to SUMO1 and catalytic activity.
Loss of enhancement of sumoylation by RWDD3. No effect on RWDD3 protein levels.
Endogenous retrovirus group V member 2 Env polyprotein
Serine palmitoyltransferase small subunit B
Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-111.
Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-108 and N-112.
Abolishes basal channel activity without affecting channel activation by a synthetic agonist; when associated with N-111 and N-112.
Constitutive active channel; abolishes inhibition by lumenal H(+); increases the pore diameter.
Constitutive active channel; abolishes inhibition by lumenal H(+); retains the Ca(2+)-dependent inactivation of the Ca(2+) current. Decreases inhibition by lumenal H(+); when associated with A-252. Decreases inhibition by lumenal H(+); when associated with A-273.
Constitutive active channel; greatly impairs inhibition by lumenal Na(+).
Decreases in Ca(2+) permeability and selectivity; decreases channel pore dynamic behavior.
Increases inhibition by lumenal H(+). Decreases inhibition by lumenal H(+); when associated with A-283.
Nearly abolishes channel activation by a synthetic agonist.
Nearly abolishes channel activity; inhibits starvation-induced autophagy.
Golgin subfamily A member 6-like protein 4
Sodium-dependent neutral amino acid transporter B(0)AT2
Found in a patient with bilateral optic nerve colobomas; uncertain pathological significance.
In FSGS7; decreased DNA-binding capability and transactivation ability.
In FSGS7; transactivation activity is dramatically decreased in presence of TLE4; dramatically enhances interaction with TLE4.
In PAPRS; the patient manifests oligomeganephronia and bilateral optic nerve coloboma.
Probable disease-associated variant found in a patient with non-syndromic renal hypodysplasia.
Opioid growth factor receptor-like protein 1
Eukaryotic translation initiation factor 2D
Abolishes sumoylation; when associated with R-114 and R-121.
Abolishes sumoylation; when associated with R-121 and R-142.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); in isoform 2
Induces a strong decrease in sumoylation; when associated with N-103. Abolishes sumoylation; when associated with R-114 and R-142.
Sumoylated and increases total protein sumoylation levels.
Abolished phosphorylation by ULK1; promotes hydrolase activity, leading to increased proteolytic activation and delipidation of ATG8 family proteins.
Decreased phosphorylation by AKT2, leading to reduced proteolytic activation of ATG8 family proteins.
Decreased phosphorylation by AKT2; when associated with A-121.
Decreased phosphorylation by AKT2; when associated with A-262.
Decreased phosphorylation, leading to decreased hydrolase activity and autophagic flux. Does not affect interaction with ATG8 family proteins.
Does not affect S-nitrosylation. Does not affect formation of disulfide bonds.
Does not affect S-nitrosylation. Strongly decreased S-nitrosylation, leading to increased hydrolase activity and autophagic flux; when associated with S-189. Reduced formation of intrachain and interchain disulfide bonds in response to oxidation. Abolished formation of disulfide bonds, leading to increased autophagy; when associated with S-361.
Does not affect S-nitrosylation. Strongly decreased S-nitrosylation, leading to increased hydrolase activity and autophagic flux; when associated with S-292. Does not affect formation of disulfide bonds.
Does not affect formation of disulfide bonds.
In 2mLIR; decreased interaction with ATG8 family proteins MAP1LC3A, MAP1LC3B and MAP1LC3C. Decreased ability to mediate delipidation of ATG8 proteins conjugated to phosphatidylethanolamine (PE).
Phospho-mimetic mutant; does not affect interaction with ATG8 family proteins.
Phospho-mimetic mutant; increased proteolytic activation of ATG8 family proteins.
Phospho-mimetic mutant; reduced hydrolase activity, leading to decreased proteolytic activation and delipidation of ATG8 family proteins.
Phospho-mimetic mutant; slightly increased interaction with ATG8 family proteins.
Reduced formation of intrachain and interchain disulfide bonds in response to oxidation. Abolished formation of disulfide bonds, leading to increased autophagy; when associated with S-292.
Reduces the redox sensitivity and retains activity in presence of H(2)O(2).
Found in patient with leukoencephalopathy; unknown pathological significance.
In LKENP; deleterious only under stress conditions.
Cilia- and flagella-associated protein 251
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C
In isoform 1S, isoform 2S, isoform 3S, isoform 4S, isoform 5S, isoform 6S, isoform 7S and isoform 8S.
Protein mono-ADP-ribosyltransferase PARP6
Ubiquitin-associated domain-containing protein 1
Monomer only, and reduced cell adhesion efficiency.
ATP-sensitive inward rectifier potassium channel 1
V-set and transmembrane domain-containing protein 2B
Restores sensitivity to extracellular protons.
Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-70.
Strongly reduced current amplitude and localization to cell membrane. Strongly reduced current amplitude and localization to cell membrane; when associated with Q-96.
DNA-directed RNA polymerase I subunit RPA2
In TCS4; unknown pathological significance.
Prostaglandin F2 receptor negative regulator
Found in a family with syndactyly, undescended testes, delayed motor milestones, intellectual disability and signs of brain atrophy; unknown pathological significance.
Sperm acrosome membrane-associated protein 6
Phosphatidylinositol-binding clathrin assembly protein
Does not affect NF-kappa-B activation and TNF production.
Hypomorphic variant resulting in impaired NF-kappa-B activation and TNF production; loss of interaction with MYD88.
The functional impact of this variant is unclear; it has been reported both to affect interaction with TLR2, hence attenuating TLR2 signal transduction and to have no effect on NF-kappa-B activation and TNF production.
Toll/interleukin-1 receptor domain-containing adapter protein
In TTD6; reduction in the levels of both TFIIE-alpha and TFIIE-beta subunits of the TFIIE complex in patient cells; reduced phosphorylation of TFIIE-alpha observed in patient cells.
Transcription initiation factor IIE subunit beta
COX assembly mitochondrial protein 2 homolog
Nicotinate-nucleotide pyrophosphorylase [carboxylating]
Immediate early response gene 5-like protein
Inhibits interaction with BLNK. Inhibits activation of several downstream signaling pathways.
Inhibits interaction with CSK. Stimulates activation of several downstream signaling pathways.
SLP adapter and CSK-interacting membrane protein
Found in a patient with MRT52; unknown pathological significance.
Gamma-aminobutyric acid receptor subunit gamma-3
In MRD60; reduced clathrin-mediated endocytosis; no effect on clathrin-coated pit location; no effect on protein stability and membrane recruitment.
Affects pyridoxal phosphate binding; loss of alanine--glyoxylate aminotransferase activity.
In HP1; abolishes alanine--glyoxylate aminotransferase activity by interfering with pyridoxal phosphate binding.
In HP1; loss of alanine--glyoxylate aminotransferase activity.
In HP1; loss of alanine--glyoxylate aminotransferase activity; decreased protein stability.
In HP1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization but improved dimerization in the presence of pyridoxal phosphate; decreased protein stability.
In HP1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; decreased protein stability.
In HP1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; decreased protein stability; causes protein aggregation.
In HP1; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; no effect on protein stability.
In HP1; loss of alanine--glyoxylate aminotransferase activity; no loss of dimerization; no effect on protein stability.
In HP1; loss of alanine--glyoxylate aminotransferase activity; reduced expression levels; decreased protein stability; protein aggregation seen in the cytosol with a decreased aggregation propensity in the presence of pyridoxal phosphate; loss of dimerization.
In HP1; prevalent mutation in the Canary islands; when associated with L-11 and M-340 on the minor AGXT allele; results in protein misfolding; decreased alanine--glyoxylate aminotransferase activity; no loss of dimerization; partial mitochondrial mistargeting.
In HP1; reduced alanine--glyoxylate aminotransferase activity; no loss of dimerization; no effect on protein stability.
In HP1; unknown pathological significance.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in loss of alanine--glyoxylate aminotransferase activity.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; decreased protein stability.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in loss of alanine--glyoxylate aminotransferase activity; reduced expression levels; decreased protein stability; protein aggregation seen in the cytosol with a decreased aggregation propensity in the presence of pyridoxal phosphate; reduced peroxisomal localization.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in loss of protein stability; loss of alanine--glyoxylate aminotransferase activity; loss of dimerization; partial mitochondrial mistargeting; intraperoxisomal protein aggregation seen.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in mitochondrial mistargeting; slight decrease in alanine--glyoxylate aminotransferase activity; loss of dimerization; partial loss of protein stability but protein stability increases in the presence of pyridoxal phosphate; causes protein aggregation.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in protein destabilization; decreased alanine--glyoxylate aminotransferase activity; no loss of dimerization; mitochondrial mistargeting.
In HP1; when associated with L-11 and M-340 on the minor AGXT allele; results in protein misfolding; decreased alanine--glyoxylate aminotransferase activity; reduced expression levels; reduced pyridoxal phosphate binding; reduced dimerization; reduced thermostability; increased propensity to aggregation; increased susceptibility to proteolytic degradation within the N-terminal region; mitochondrial mistargeting; exposure to pyridoxine can rescue the functionality by partially preventing aggregation and degradation and by redirecting all the protein to the peroxisome.
No loss of alanine--glyoxylate aminotransferase activity.
Reduction of specific alanine--glyoxylate aminotransferase activity in vitro; causes mitochondrial mistargeting when associated with R-170.
Altered Golgi structure with an engorged lumen. Interacts with ARFIP2, GOLGA4, RGPD8, SCOC and UNC119.
Loss of interaction with ARFIP1 and ARFIP2.
In SRTD7 and SRTD7/20; the SRTD7/20 patient also carries variant INTU 276-Q--L-942 del; chondrocyte cell lines from a patient show a reduction of cilia indicating a defect in ciliogenesis.
In SRTD7; chondrocyte cell lines from the patient show a reduction of cilia indicating a defect in ciliogenesis.
Single-pass membrane and coiled-coil domain-containing protein 4
Beta-1,3-N-acetylglucosaminyltransferase manic fringe
Cancer/testis antigen family 45 member A10
tRNA (guanine(26)-N(2))-dimethyltransferase
Abolishes protease activity, prevents processing and alters localization to the plasma membrane of N-terminal fragment.
Rhomboid-related protein 2, C-terminal fragment
Rhomboid-related protein 2, N-terminal fragment
In CTRCT15; loss of plasma membrane expression.
In CTRCT15; non-progressive lamellar cataract; loss of activity.
In CTRCT15; progressive polymorphic and lamellar cataract; loss of activity.
In CTRCT15; reduces cell-to-cell adhesion, reduces cell-to-cell gap junction coupling, no loss of cell membrane localization, no loss of water channel activity.
In CTRCT15; unknown pathological significance.
In CTRCT15; unknown pathological significance; loss of plasma membrane expression.
Complete loss of Nipah protein G binding.
(3S)-3-hydroxyasparagine; by HIF1AN; partial
Formation of an artifactual disulfide bond with PSEN1.
Loss of proteolytic cleavage by gamma-secretase.
Neurogenic locus notch homolog protein 1
O-linked (GalNAc...) threonine; alternate
Abolishes methyltransferase activity on p53/TP53.
No effect on methyltransferase activity on p53/TP53.
Reduces methyltransferase activity on p53/TP53.
Slightly reduces methyltransferase activity on p53/TP53.
Strongly reduces methyltransferase activity on p53/TP53.
Strongly reduced activation of NF-kappa-B.
CCR4-NOT transcription complex subunit 10
Loss of microtubule binding, no loss of centrosomal localization, little effect on microtubule stability, loss of ability to block centriole reduplication and defective blocking of normal centriole duplication; when associated with 189-A--A-195; 232-A--A-238 and 306-A--A-312.
Loss of microtubule binding, no loss of centrosomal localization, little effect on microtubule stability, loss of ability to block centriole reduplication and defective blocking of normal centriole duplication; when associated with 9-A--A-15; 189-A--A-195 and 232-A--A-238.
Loss of microtubule binding, no loss of centrosomal localization, little effect on microtubule stability, loss of ability to block centriole reduplication and defective blocking of normal centriole duplication; when associated with 9-A--A-15; 189-A--A-195 and 306-A--A-312.
Loss of microtubule binding, no loss of centrosomal localization, little effect on microtubule stability, loss of ability to block centriole reduplication and defective blocking of normal centriole duplication; when associated with 9-A--A-15; 232-A--A-238 and 306-A--A-312.
ST]-E-Y-X(3)-F motif 1; required for efficient microtubule binding and stabilization
ST]-E-Y-X(3)-F motif 2; required for efficient microtubule binding and stabilization
ST]-E-Y-X(3)-F motif 3; required for efficient microtubule binding and stabilization
ST]-E-Y-X(3)-F motif 4; required for efficient microtubule binding and stabilization
Abolishes binding to PTPN6 and PTPN11. Increases binding of red blood cells.
Complete loss of phosphorylation by LCK.
More than 50% loss of phosphorylation by LCK.
Significant loss of binding to peripheral blood granulocytes.
Zinc finger C2HC domain-containing protein 1B
Fibroblast growth factor-binding protein 2
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1
4-trimethylaminobutyraldehyde dehydrogenase
4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed
N-acetylserine; in 4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed
Neuronal acetylcholine receptor subunit alpha-9
The CHRNA9-CHRNA10 receptor is 250-fold more potently inhibited by the alpha-conotoxin RgIA.
Soluble interleukin-15 receptor subunit alpha
Lymphocyte function-associated antigen 3
Loss of LGR4/5/6-binding, no effect on WNT3A signaling; when associated with A-106.
Loss of LGR4/5/6-binding, no effect on WNT3A signaling; when associated with A-110.
In isoform Alpha-6X1A and isoform Alpha-6X1B.
In isoform Alpha-6X1A, isoform Alpha-6X2A, isoform Alpha-6X1X2A, isoform 7 and isoform 9.
In isoform Alpha-6X2A, isoform Alpha-6X2B and isoform 7.
Loss of interaction with CCDC8. Decreased affinity for HDAC4.
Does not restore in vitro translation, does not replace endogenous yeast enzyme.
Does not restore in vitro translation, probably does not bind BN.
In TTD7; loss of protein stability; loss of threonine-tRNA ligase activity.
Partially restores in vitro translation.
Has no effect on the catalytic activity.
Loss of ability to catalyze the formation of 1-methyladenosine at position 947 of mitochondrial 16S ribosomal RNA.
tRNA (adenine(58)-N(1))-methyltransferase, mitochondrial
CXXC motif containing zinc binding protein
Disrupts protein folding and solubility; when associated with A-33; A-36 and A-67.
Disrupts protein folding and solubility; when associated with A-33; A-36 and A-70.
Disrupts protein folding and solubility; when associated with A-33; A-67 and A-70.
Disrupts protein folding and solubility; when associated with A-36; A-67 and A-70.
Abolishes autophosphorylation. Abolishes interaction with SRC.
Loss of phosphorylation site. Strongly reduced interaction with GRB2.
Melanocortin-2 receptor accessory protein
Heterogeneous nuclear ribonucleoprotein L-like
Cilia- and flagella-associated protein 53
In HTX6; unknown pathological significance.
Mitochondrial coenzyme A diphosphatase NUDT8
Nuclear envelope phosphatase-regulatory subunit 1
Interferon-induced protein with tetratricopeptide repeats 2
Significantly impairs RNA-binding; when associated with Glu-255.
Significantly impairs RNA-binding; when associated with Glu-259.
CKLF-like MARVEL transmembrane domain-containing protein 8
Protein kinase C delta type catalytic subunit
Protein kinase C delta type regulatory subunit
In LEPD; no effect on secretion; does not bind or activate LEPR.
Putative tyrosine-protein phosphatase TPTE
Abolishes cleavage to yield frataxin intermediate form and allows accumulation of frataxin(56-210) and frataxin(78-210).
Abolishes cleavage to yield frataxin mature form and allows accumulation of frataxin(56-210) and frataxin(78-210).
Abolishes cleavage to yield frataxin mature form and allows the accumulation of frataxin(56-210).
Does not affect interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
Drasticly reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
In FRDA; mild form; decreases affinity for the SDAU complex by 40-fold; decreases the level of covalent incorporation of sulfur into both NFS1 and ISCU.
In FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel; a murine cellular FRDA model, deleted for endogenous frataxin and expressing human mutant frataxin cDNA shows defects in mitochondrial structure, mitochondrial iron deposits, decreased enzymatic activity of some mitochondrial and cytoplasmic iron-sulfur cluster-containing enzymes, increased RNA-binding activity of ACO1 and increased sensitivity to oxidative stress; decreases the level of covalent incorporation of sulfur into both NFS1 and ISCU.
In FRDA; reduces interaction with LYRM4; the interaction is rescued by nickel; drastically decreases affinity for the SDAU complex by > 75-fold; decreases the level of covalent incorporation of sulfur into both NFS1 and ISCU.
Loss of interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
No effect on processing of wild-type FXN.
Reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
Significantly reduces interaction with the core iron-sulfur cluster assembly complex. Does not affect mitochondrial localization. Does not affect proteolytic processing.
In CMH8; with mid-left ventricular chamber thickening.
Translation machinery-associated protein 16
Coiled-coil domain-containing protein 91
Interchain (with C-208); in dimeric form
Interchain (with C-215); in dimeric form
In PNLIPD; loss of function in lipid catabolic process; the mutant is not secreted.
Completely abolishes potentiation and activation by the agonist alphaxalone.
Gamma-aminobutyric acid receptor subunit alpha-1
In EIG13; the mutant protein is partially retained in the endoplasmic reticulum and has decreased expression at the plasma membrane; causes decreased current amplitude in response to GABA compared to wild-type and alters receptor gating kinetics including faster desensitization.
Reduced potentiation and activation by the agonist alphaxalone.
Transforming growth factor beta regulator 1
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 9 and isoform 10.
In isoform 3, isoform 5, isoform 7 and isoform 9.
Alpha-N-acetylglucosaminidase 77 kDa form
Alpha-N-acetylglucosaminidase 82 kDa form
In MPS3B; accounts for approximately 20% of MPS3B alleles in a Dutch patient group.
In MPS3B; accounts for approximately 6% of mutations in Australasian patients with MPS3B.
In MPS3B; accounts for approximately 6% of the mutant alleles in Australasian patients with MPS3B.
In MPS3B; associated with a partially degraded polypeptide in a 16-hour chase experiment suggesting that L-48 NAGLU affects the processing and stability of the gene; some L-48 NAGLU is being correctly sorted to the lysosomal compartment.
In MPS3B; decreases the enzyme activity markedly.
In MPS3B; no enzyme activity; synthesizes a polypeptide with a molecular size similar to that of the wild-type.
In MPS3B; produces 12.7% residual enzyme activity.
In MPS3B; unknown pathological significance.
In MRT69; impaired localization to the nucleolus.
Zinc finger and BTB domain-containing protein 11
Medium-chain acyl-CoA ligase ACSF2, mitochondrial
(3S)-3-hydroxyhistidine; by HIF1AN; partial
Poly [ADP-ribose] polymerase tankyrase-2
Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912, G-915 and L-920.
Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912, L-920 and G-923.
Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-912,G-915 and G-923.
Disrupts interaction with Rab7, translocation to cytoplasm; when associated with G-915, L-920 and G-923.
Run domain Beclin-1-interacting and cysteine-rich domain-containing protein
Putative ADP-ribosylation factor-like protein 5C
39S ribosomal protein L35, mitochondrial
Found in patients with isolated growth hormone deficiency.
In IGHD1B; reduced ability to activate the JAK/STAT pathway.
In KWKS; no effect on GHR signaling pathway; does not affect interaction with GHR; results in a stronger interaction with GHBP; does not affect subcellular location.
In short stature; idiopathic autosomal; affects binding affinity of GH for GHR and the potency of GH to activate the JAK2/STAT5 signaling pathway.
In BDPLT19; patient platelets show impaired activation.
cAMP-dependent protein kinase catalytic subunit gamma
In CAFBN; abolishes fibrinogen secretion.
In CAFBN; homozygous; heterozygous; no effect on fibrinogen complex assembly; impaired fibrinogen complex secretion.
In CAFBN; hypofibrinogenemia; heterozygous; decreased fibrinogen complex assembly; no effect on fibrinogen complex secretion.
In Christchurch-2, Seattle-1 and Ijmuiden.
In DYSFIBRIN; fibrinogen Naples and Milano-2; associated with defective thrombin binding and thrombophilia.
DNA (cytosine-5)-methyltransferase 3-like
In CPSQ3; decreased actin capping activity; increased fibroblast proliferation and migration; decreased colocalization with alpha subunit ADD1.
Peptidyl-prolyl cis-trans isomerase FKBP7
Reduces enzyme activity. Abolishes enzyme activity; when associated with A-160.
Strongly reduces enzyme activity. Abolishes enzyme activity; when associated with A-183.
Abolished non-canonical autophagy without affecting canonical autophagy.
Abolished non-canonical autophagy without affecting canonical autophagy. Impaired conjugation of phosphatidylserine (PS) to LC3 proteins.
Abolishes phosphorylation. Impairs interaction with ATG12-ATG5 complex.
Impairs interaction with PPP1CA; when associated with A-540.
Impairs interaction with PPP1CA; when associated with A-542.
In FII mutant; abolished binding to membranes and lipidation to ATG8 family proteins.
In IBD10; has no effect on the stability of the protein under normal conditions; enhances the cleavage and the degradation mediated by activated CASP3; results in reduced autophagy and defective clearance of intestinal pathogens; impairs interaction with TMEM59; slows TMEM59 intracellular trafficking; increases production of type I IFNs.
In VRV mutant; abolished binding to membranes and lipidation to ATG8 family proteins.
Abrogates ATM-dependent phosphorylation.
Abrogates ATM-dependent phosphorylation. No loss of interaction with KPNA2.
Blocks the association with KPNA2, and reduces nuclear foci formation in response to ionizing radiation.
Disrupts nuclear foci formation and block phosphorylation in response to ionizing radiation.
In some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant.
In some childhood acute lymphoblastic leukemia patients; uncertain pathological significance; rare variant; associated with aplastic anemia at homozygosity.
Bile acid-CoA:amino acid N-acyltransferase
In BACD1; contrary to wild-type, undetectable expression in hepatocytes.
In BACD1; unknown pathological significance.
In BACD1; unknown pathological significance; contrary to wild-type, undetectable expression in hepatocytes.
Lowers N-acyltransferase activity; enhanced thioesterase activity presumably dependent on the formation of a bile acid-enzyme covalent intermediate via a thioester bond.
Abolished ubiquitination and degradation by the DCX(TRPC4AP) complex.
Impairs interaction with FBXW7 and subsequent degradation by the proteasome. Impaired inhibition of Ras-induced senescence. Abolishes phosphorylation by DYRK2, and subsequent phosphorylation by GSK3B at Thr-58.
Impairs interaction with FBXW7 and subsequent degradation by the proteasome. Normal inhibition of Ras-induced senescence.
Phospho-mimetic mutant; abolished regulation by AMBRA1.
In DEE34; results in loss of chloride transport; decreased localization at the cell surface.
In DEE34; results in reduced chloride transport; decreased localization at the cell surface.
In EIG14; rare variant associated with disease susceptibility; results in reduced chloride transport.
In EIG14; rare variant associated with disease susceptibility; results in reduced chloride transport; decreased localization at the cell surface; unable to induce cortical dendritic spines formation.
In JBTS39; fails to rescue the ciliopathy phenotype in a zebrafish disease model.
In JBTS39; unknown pathological significance.
Probable disease-associated variant found in patients with Meckel syndrome.
Abolishes mitotic phosphorylation; when associated with A-222.
Abolishes mitotic phosphorylation; when associated with A-225.
Abolishes myristoylation. Loss of its ability to mediate unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane. No effect on ER stress-induced relocalization from Golgi to ER.
Abolishes organelle clustering; when associated with A-59.
Abolishes organelle clustering; when associated with S-100.
Enhances homodimerization. Loss of ER stress-induced relocalization from Golgi to ER.
Loss of phosphorylation and its ability to mediate unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane. Inhibits ER stress-mediated disruption of homodimerization. Loss of ER stress-induced relocalization from Golgi to ER.
Loss of phosphorylation. Does not inhibit ER stress-mediated disruption of homodimerization.
Phosphomimetic mutant. No disruption of homodimerization.
Phosphomimetic mutant. No loss of its ability to mediate unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane. Disrupts homodimerization. No loss of ER stress-induced relocalization from Golgi to ER.
Phosphomimetic mutant. Partial disruption of homodimerization.
Phosphomimetic mutation that decreases the ability to promote organelle clustering.
Abolished E3 ubiquitin-protein ligase activity.
Rab GTPase-activating protein 1-like, isoform 10
Abolishes the formation of poly(SUMO) chains.
Impaired interaction with USP25; when associated with A-33.
Impaired interaction with USP25; when associated with A-34.
Putative POU domain, class 5, transcription factor 1B
High-affinity association with the preproteasome
Lysosomal-associated transmembrane protein 5
In CDCBM5; abolishes coassembly with tubulin subunits and incorporation into the microtubule polymer network.
In CDCBM5; reduces coassembly with tubulin subunits and incorporation into the microtubule polymer network.
NK1 transcription factor-related protein 1
In PARK19B; patient fibroblasts show decreased levels of the protein.
Putative tyrosine-protein phosphatase auxilin
Abolishes interaction with BCR-ABL SH3 domain.
Nuclear envelope integral membrane protein 1
Tumor necrosis factor ligand superfamily member 12, membrane form
Tumor necrosis factor ligand superfamily member 12, secreted form
Tubulin polyglutamylase complex subunit 1
Impairs interaction with the TFIIH complex.
Impairs transcription-coupled nucleotide excision repair ability.
In UVSS3; mild phenotype; impairs transcription-coupled nucleotide excision repair ability.
Leucine-rich repeat and fibronectin type-III domain-containing protein 3
Phosphoserine; by MAPKAPK2 or MAPKAPK3; in vitro
No effect on BCL2-binding; when associated with A-35.
No effect on BCL2-binding; when associated with A-36.
No effect on BCL2-binding; when associated with A-38.
No effect on BCL2-binding; when associated with A-39.
No effect on BCL2-binding; when associated with A-43.
No effect on BCL2-binding; when associated with A-44.
No effect on BCL2-binding; when associated with A-45.
No effect on BCL2-binding; when associated with A-46.
Reduced BCL2-binding and reduced pro-apoptotic activity; when associated with A-57. No effect on mitochondrial localization; when associated with A-57.
Reduced BCL2-binding and reduced pro-apoptotic activity; when associated with A-58. No effect on mitochondrial localization; when associated with A-58.
Reduced BCL2-binding; when associated with A-50.
Reduced BCL2-binding; when associated with A-51.
Reduced BCL2-binding; when associated with A-54.
Reduced BCL2-binding; when associated with A-55.
Golgi apparatus membrane protein TVP23 homolog C
Ribonucleoside-diphosphate reductase large subunit
Severely decreases interaction with AHCYL1 in the presence of dATP.
Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-28 and A-30.
Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-28 and A-32.
Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-30 and A-32.
SH3 and multiple ankyrin repeat domains protein 1
Abolishes phosphorylation by CDK1 and reduces REPS2 binding.
Protein phosphatase 1 regulatory subunit 14D
Reduces inhibitory activity by 16%. Reduces phosphorylation.
In SEMDAG; creates a functional N-glycosylation site; does not adversely affect protein trafficking and secretion.
O-linked (Xyl...) (keratan sulfate) threonine
Low-density lipoprotein receptor-related protein 3
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial
Caspase-14 subunit p20, intermediate form
Caspase-14 subunit p8, intermediate form
Strongly decreased hyaluronidase activity.
Pregnancy-specific beta-1-glycoprotein 5
Zinc finger TRAF-type-containing protein 1
Nuclear factor related to kappa-B-binding protein
Neuronal acetylcholine receptor subunit alpha-4
Decrease in the retinaldehyde reductase activity. Exhibits changes in both KM and kcat values.
Decreases in the retinaldehyde reductase activity. 3-fold decrease in the kcat value, whereas the KM value does not vary.
Loss of interaction with PSIP1; when associated with A-476.
Loss of interaction with PSIP1; when associated with A-477.
Phosphomimetic mutant. Moderate increase in interaction with PSIP1.
Abolishes lysine-specific histone demethylase activity.
Dolichyl-phosphate beta-glucosyltransferase
In VDDR2A; decreased calcitriol receptor activity; decreased affinity for calcitriol; decreased ligand-independent localization to the nucleus; loss of interaction with RXRA; decreased interaction with NCOR1; decreased interaction with NCOA1; decreased sequence-specific DNA-binding.
In VDDR2A; loss of calcitriol receptor activity; decreased affinity for calcitriol by a factor of 1000; no effect on interaction with RXRA; changed interaction with NCOR1; loss of interaction with NCOA1; no effect on sequence-specific DNA-binding.
In VDDR2A; loss of calcitriol receptor activity; loss of affinity for calcitriol; decreased ligand-independent localization to the nucleus; loss of interaction with RXRA; loss of interaction with NCOR1; loss of interaction with NCOA1; loss of sequence-specific DNA-binding.
In VDDR2A; loss of calcitriol receptor activity; loss of affinity for calcitriol; no effect on ligand-independent localization to the nucleus.
In VDDR2A; loss of calcitriol receptor activity; no effect on interaction with RXRA; changed interaction with NCOR1; loss of interaction with NCOA1; no effect on sequence-specific DNA-binding.
Promotes heterodimerization with RXRA; when associated with A-61 and A-62.
Promotes heterodimerization with RXRA; when associated with A-75.
In AGU; most frequent mutation; abolishes autocatalytic cleavage and enzyme activity.
In AGU; specifically prevents the proteolytic activation cleavage of AGA in the endoplasmic reticulum.
In AGU; uncertain pathological significance.
Loss of ion transport activity; Does not rescue insulin secretion defect induced by knockdown of SLC9B2 in Min6 cells.
Found in patients with a phenotype suggestive of Stickler syndrome; unknown pathological significance.
Low-density lipoprotein receptor-related protein 2
PxLPxI/L motif 1; mediates interaction with ANKRA2
PxLPxI/L motif 2; mediates interaction with ANKRA2
N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 3
Microtubule-associated serine/threonine-protein kinase 3
In EDMD6; drastically reduced protein levels in muscle.
In RBMX1A; the mutant protein initiates aggregation of the FHL1 protein causing reducing bodies formation; dominant-negative effect.
In RBMX1A; unknown pathological significance.
In RBMX1B; unknown pathological significance.
In XMPMA; unknown pathological significance.
Loss of catalytic activity. Slight reduction in protein stability.
Moderate reduction in catalytic activity. Reduces protein stability.
No effect on catalytic activity or protein stability.
Signal peptidase complex catalytic subunit SEC11A
Slight reduction in catalytic activity; when associated with D-97.
Slight reduction in catalytic activity; when associated with R-116.
Small integral membrane protein 10-like protein 2A
Small integral membrane protein 10-like protein 2B
Found in a patient with Moyamoya disease; unknown pathological significance.
No effect on interaction with BTRC and FBXW11.
Strongly decreases interaction with BTRC and FBXW11 and inhibits degradation promoted by CSNK1E.
Strongly decreases interaction with BTRC and FBXW11.
Ability to bind capped mRNA reduced to 13% of wild-type.
Ability to bind capped mRNA reduced to 40% of wild-type.
Ability to bind capped mRNA reduced to less than 10% of wild-type.
Does not affect ubiquitination by ARIH1; when associated with R-121; R-130 and R-134.
Does not affect ubiquitination by ARIH1; when associated with R-121; R-130 and R-222.
Does not affect ubiquitination by ARIH1; when associated with R-121; R-134 and R-222.
Does not affect ubiquitination by ARIH1; when associated with R-130; R-134 and R-222.
Eukaryotic translation initiation factor 4E type 2
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); alternate
Slight reduction in ability to bind capped mRNA.
Developmental pluripotency-associated protein 3
Correlated with reduced enzyme activity; associated with increased risk for schizophrenia.
In allele COMT*2; associated with low enzyme activity and thermolability; may increase the tendency to develop high blood pressure and abdominal obesity.
26S proteasome non-ATPase regulatory subunit 3
May be associated with susceptibility to IDD.
Removed in 64 kDa matrix metalloproteinase-9 and 67 kDa matrix metalloproteinase-9
Loss of plasmanylethanolamine desaturase activity.
No effect on desaturase plasmanylethanolamine activity.
No effect on plasmanylethanolamine desaturase activity.
2-oxoglutarate and iron-dependent oxygenase domain-containing protein 3
Inactive Rho GTPase-activating protein 11B
In COXPD39; unknown pathological significance; may affect splicing.
Ribosome-releasing factor 2, mitochondrial
ATP-binding cassette sub-family F member 3
Abolished tyrosine carboxypeptidase activity. No effect on binding to microtubule.
Disrupted interaction with SVBP. Reduced tyrosine carboxypeptidase activity.
No effect on tyrosine carboxypeptidase activity.
Reduced tyrosine carboxypeptidase activity.
Slightly reduced tyrosine carboxypeptidase activity.
Strongly reduced tyrosine carboxypeptidase activity.
Na(+)/H(+) exchange regulatory cofactor NHE-RF3
Peripheral-type benzodiazepine receptor-associated protein 1
In GAN2; interaction with DDB1 is decreased.
Leucine-rich single-pass membrane protein 2
In DIAR3; has a significantly reduced ability to inhibit trypsin compared to wild-type.
In P3-D3A mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with A-28 and A-175.
In P3-D3A mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with A-9 and A-175.
In P3-D3A mutant; abolished cleavage and activation, leading to prevent thiol protease activity; when associated with A-9 and A-28.
Methionine-R-sulfoxide reductase B2, mitochondrial
Intraflagellar transport protein 80 homolog
High affinity cationic amino acid transporter 1
Abolished interaction with XRCC5/Ku80 and XRCC6/Ku70.
Abolishes the association with the non-homologous end joining complex and localization to double-strand break sites. Abolished interaction with XRCC6/Ku70.
Abolishes the association with the non-homologous end joining complex.
Abolishes the association with the non-homologous end joining complex. Abolished interaction with XRCC6/Ku70.
Does not affect interaction with the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when associated with 145-D--152.
Does not affect interaction with the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when associated with A-134.
Loss of function in DNA non-homologous end joining (NHEJ).
Phospho-mimetic mutant; abolished interaction with DNA-bound the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when associated with 145-D--152.
Phospho-mimetic mutant; abolished interaction with the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer; when associated with D-134.
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC.
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A soluble form
N-linked (GlcNAc...) asparagine; atypical
Ras-specific guanine nucleotide-releasing factor RalGPS1
Oxidative stress-induced growth inhibitor 1
Probable ATP-dependent RNA helicase DDX27
Required for interaction with the PEBOW complex
Cilia- and flagella-associated protein 206
Loss of TSG101-binding and drastic reduction of TSG101-ubiquitination.
Ankyrin repeat domain-containing protein 35
Impaired association with protein kinase PRKCG but not with SRC.
Putative 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase
In DBA18; unknown pathological significance.
Amyloid-beta A4 precursor protein-binding family B member 3
Abolishes cholesterol and 25-hydroxycholesterol binding. Abolishes cholesterol transfer from NPC2 to NPC1.
Abolishes cholesterol transport. No effect on subcellular location.
Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-92.
Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-88 and A-96.
Decreased affinity for NPC2 and decreased cholesterol transfer from NPC2 to NPC1; when associated with A-92 and A-96.
Decreases affinity for NPC2. Abolishes cholesterol transfer from NPC2 to NPC1.
In NPC1; decreased affinity for NPC2; decreased cholesterol transfer from NPC2 to NPC1.
In NPC1; found in the Nova Scotian clinical variant.
In NPC1; late infantile form; Common in Japanese.
In NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clears the lysosomal cholesterol accumulation in NPC1-deficient cells.
Loss of interaction with ebolavirus glycoprotein.
NPC intracellular cholesterol transporter 1
Nearly abolishes 25-hydroxycholesterol binding. Reduces cholesterol binding.
Nearly abolishes cholesterol and 25-hydroxycholesterol binding.
No effect on cholesterol and 25-hydroxycholesterol binding and transfer.
No effect on cholesterol or 25-hydroxycholesterol binding. Decreases affinity for NPC2. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner.
No effect on cholesterol or 25-hydroxycholesterol binding. Nearly abolishes cholesterol transfer to liposomes in a NPC2-dependent manner.
No effect on function; colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells.
Reduces glycosylation; when associated with Q-122 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding.
Reduces glycosylation; when associated with Q-70 and Q-122. No effect on cholesterol and 25-hydroxycholesterol binding. Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner.
Reduces glycosylation; when associated with Q-70 and Q-185. No effect on cholesterol and 25-hydroxycholesterol binding.
Strongly reduces 25-hydroxycholesterol binding and cholesterol transfer to liposomes in a NPC2-dependent manner.
Strongly reduces 25-hydroxycholesterol binding. No effect on cholesterol binding.
Strongly reduces cholesterol and 25-hydroxycholesterol binding.
Strongly reduces cholesterol transfer to liposomes in a NPC2-dependent manner.
Strongly reduces interaction with ebolavirus glycoprotein.
In SCAN3; results in increased proteasomal degradation; decreased protein levels; decreased amount of protein imported in the mitochondrion intermembrane space.
In SCAN3; unknown pathological significance.
Tumor necrosis factor ligand superfamily member 13b, membrane form
Tumor necrosis factor ligand superfamily member 13b, soluble form
In CDG1T; decreases strongly solubility.
In CDG1T; reduces mildly phosphoglucomutase activity.
In CDG1T; reduces solubility; increases aggregation.
In CDG1T; reduces solubility; reduces strongly phosphoglucomutase activity.
In CDG1T; reduces strongly phosphoglucomutase activity.
In CDG1T; reduces strongly solubility; increases aggregation.
In CDG1T; there is 7% enzyme residual phosphoglucomutase activity.
In allele PGM1*1-, allele PGM1*2-, allele PGM1*3- and allele PGM1*7-; phosphoglucomutase activity is similar to wild-type.
In allele PGM1*2+, allele PGM1*2-, allele PGM1*3+ and allele PGM1*3-; phosphoglucomutase activity is similar to wild-type.
In allele PGM1*7+, allele PGM1*7-, allele PGM1*3+ and allele PGM1*3-; phosphoglucomutase activity is similar to wild-type.
In HIDEA; unknown pathological significance.
DNA-directed RNA polymerases I, II, and III subunit RPABC3
Decreased iron-binding. Loss of iron-binding; when associated with L-86.
Loss of deoxyhypusine monooxygenase activity. Loss of iron-binding.
Loss of deoxyhypusine monooxygenase activity. No effect on iron-binding.
No effect on iron-binding. Loss of iron-binding; when associated with L-237.
In WARBM3; abnormal endoplasmic reticulum structure; in fibroblasts ER spread away from the perinuclear region into the cell periphery and there is a loss of fragmentation of ER tubules.
In WARBM3; unknown pathological significance.
Loss of localization to lipid droplets and interaction with ZFYVE1.
No loss of localization to lipid droplets and interaction with ZFYVE1.
In DBA5; may result in aberrant splicing.
In DA5; causes slowing of inactivation of PIEZO2-dependent mechanically activated currents as well as significantly faster recovery from inactivation compared to wild-type.
In DA5; recovers faster from inactivation.
Piezo-type mechanosensitive ion channel component 2
In IFAP1; does not affect subcellular localization; impairs activity.
In KFSDX; sterol responsiveness is reduced by half.
In OI19; decreased regulated intramembrane proteolysis resulting in reduced transcriptional activation of genes relevant to osteoblast differentiation and bone formation.
Membrane-bound transcription factor site-2 protease
In MTDPS2 and PEOB3; reduction of activity; reduced affinity for ATP.
In MTDPS2; reduction of activity in muscles.
In MTDPS2; severe form of combined brain and muscular atrophy; depletion of mtDNA in skeletal muscle; normal residual mtDNA in blood and fibroblasts.
In PEOB3; reduction of activity; reduced affinity for ATP.
Abolishes ATP dependent microtubule severing activity and localization to spindle poles.
Abolishes ATP dependent microtubule severing activity and localization to spindle poles; when associated with N-308.
Abolishes ATP dependent microtubule severing activity and localization to spindle poles; when associated with N-309.
Katanin p60 ATPase-containing subunit A1
Peptidyl-prolyl cis-trans isomerase FKBP11
Reduced interaction with H3C15 and H3C1.
Zinc finger protein with KRAB and SCAN domains 1
Sperm protein associated with the nucleus on the X chromosome N3
Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q
Does not bind alpha subunit. Loss of ability to protect alpha subunit from inhibition by the spider protoxin-II.
Found in a patient with Brugada syndrome; unknown pathological significance; induces a reduction in sodium current density most likely by decreasing SCN5A protein cell surface expression.
In ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system.
Increases cell surface expression and NPS-dependent calcium mobilization; does not affect affinity for NPS..
Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP.
Impairs binding to IL18R1 and the ability to induce IFNG production.
Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production.
Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP.
Reduces binding to IL18R1 and the ability to induce IFNG production.
Impairs bending of target DNA. Strongly reduced DNA cleavage.
O-(5'-phospho-DNA)-tyrosine intermediate
Reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding.
Strongly reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding.
Ras-related and estrogen-regulated growth inhibitor
C-1-tetrahydrofolate synthase, cytoplasmic
C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed
Decreased methylenetetrahydrofolate dehydrogenase (NADP+) activity over 90%. Loss of methenyltetrahydrofolate cyclohydrolase activity.
In NTDFS; associated with disease susceptibility.
In NTDFS; associated with disease susceptibility; increases risk for congenital heart defects; decreased enzyme stability; no effect on methylenetetrahydrofolate dehydrogenase (NADP+) activity; no effect on formyltetrahydrofolate synthetase activity.
Moderate decrease of methylenetetrahydrofolate dehydrogenase (NADP+) activity. Loss of methenyltetrahydrofolate cyclohydrolase activity. Strongly decreased affinity for NADP. Increased affinity for 5,10-methenyltetrahydrofolate.
No effect on methylenetetrahydrofolate dehydrogenase (NADP+) activity. No effect on methenyltetrahydrofolate cyclohydrolase activity. Decreased affinity for NADP.
Reduced methylenetetrahydrofolate dehydrogenase (NADP+) activity by 50%. Reduced methenyltetrahydrofolate cyclohydrolase activity by 87%.
Reduced methylenetetrahydrofolate dehydrogenase (NADP+) activity by 75%. Reduced methenyltetrahydrofolate cyclohydrolase activity by 99%. No effect on affinity for NADP and 5,10-methenyltetrahydrofolate.
Reduced methylenetetrahydrofolate dehydrogenase (NADP+) activity by 99%. Reduced methenyltetrahydrofolate cyclohydrolase activity by 70%. No effect on affinity for NADP and 5,10-methenyltetrahydrofolate.
Reduced methylenetetrahydrofolate dehydrogenase (NADP+) activity. Reduced methenyltetrahydrofolate cyclohydrolase activity by 99%. No effect on affinity for NADP and 5,10-methenyltetrahydrofolate.
Slightly reduced methylenetetrahydrofolate dehydrogenase (NADP+) activity. Slightly reduced methenyltetrahydrofolate cyclohydrolase activity. Decreased affinity for NADP and for 5,10-methenyltetrahydrofolate.
tRNA (uracil-5-)-methyltransferase homolog B
Abolishes ubiquitin transfer; when associated with A-848.
Abolishes ubiquitin transfer; when associated with A-855.
NEDD4-like E3 ubiquitin-protein ligase WWP1
Reduces ubiquitin transfer. Strongly reduces ubiquitin transfer; when associated with A-845.
Strongly reduces ubiquitin transfer; when associated with P-804.
Strongly reduces ubiquitin transfer; when associated with P-806.
Abolishes AP endodeoxyribonuclease activity.
Abolishes AP endodeoxyribonuclease activity. Lacks MYC CRD RNA cleavage activity.
Abolishes the AP endodeoxyribonuclease activity.
Abolishes the AP endodeoxyribonuclease activity. Reduces protection from granzyme A-mediated cell death; when associated with A-31 and A-65.
Abolishes the redox activity. Does not abolish the AP endodeoxyribonuclease and phosphodiesterase activities. Reduces protection from granzyme A-mediated cell death; when associated with A-31 and A-210.
DNA-(apurinic or apyrimidinic site) endonuclease
DNA-(apurinic or apyrimidinic site) endonuclease, mitochondrial
Decreases AP endodeoxyribonuclease activity.
Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-310.
Does not abolish NO-induced nitrosylation. Abolishes NO-induced nitrosylation and translocation from the nucleus to the cytoplasm; when associated with S-93.
Does not abolish NO-induced nitrosylation. Enhances NO-induced nuclear export.
Enhances the interaction with TOMM20. Does not inhibit redox and AP endodeoyribonuclease activities. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-25; A-27 and A-32. Reduces protection from granzyme A-mediated cell death; when associated with A-65 and A-210.
Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-27; A-31 and A-32. Inhibits ubiquitination; when associated with K-24 and K-27.
Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-25; A-27; A-31 and A-32. Inhibits ubiquitination; when associated with K-25 and K-27.
Enhances the interaction with TOMM20. Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoyribonuclease activity; when associated with A-24; A-25; A-31 and A-32. Inhibits ubiquitination; when associated with K-24 and K-25.
Inhibits rRNA binding, interaction with NPM1, nuclear localization and modulates its endodeoxyribonuclease activity; when associated with A-24; A-25; A-27 and A-31.
Lack of acetylation and does not stimulate the YBX1-mediated MDR1 promoter activity and alter nuclear subcellular localization; when associated with R-6.
Lack of acetylation, does not stimulate the YBX1-mediated MDR1 promoter activity and alter nuclear subcellular localization; when associated with R-7. Does not inhibit interaction with HDAC1, HDAC2 and HDAC3. Absence of increase in nCaRE binding activity.
Nearly abolishes AP endodeoxyribonuclease activity.
Reduces AP endodeoxyribonuclease activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-283.
Reduces nuclear localization; when associated with A-12.
Reduces nuclear localization; when associated with A-13.
Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-299.
Reduces the interaction with TOMM20. Abolishes localization in the mitochondria; when associated with A-301.
Strongly reduces AP endodeoxyribonuclease activity, but does not affect RNA cleavage activity. Nearly abolishes AP endodeoxyribonuclease activity; when associated with A-308.
Strongly reduces AP endodeoxyribonuclease activity.
'Ionic lock' involved in activated form stabilization
Found in a patient with retinitis pigmentosa; unknown pathological significance.
Found in patients with pathologic myopia; unknown pathological significance.
In CSNBAD1; constitutive activity in the absence of bound retinal.
In RP4; most common variant; impairs protein folding; leads to interaction with EDEM1 followed by degradation by the ERAD system.
Induces a conformation change that promotes interaction with GRK1 and SAG; when associated with Q-113.
Induces a conformation change that promotes interaction with GRK1 and SAG; when associated with Y-257.
Loss of phosphorylation sites and decreased interaction with SAG.
Loss of phosphorylation sites and decreased interaction with SAG; when associated with 336-A--A-338.
Loss of phosphorylation sites and decreased interaction with SAG; when associated with A-343.
15-hydroxyprostaglandin dehydrogenase [NAD(+)]
Loss 15-hydroxyprostaglandin dehydrogenase activity.
Reduced affinity for NAD and prostaglandin E2.
ATP-binding cassette sub-family A member 6
110-fold reduction in catalytic activity.
3.5-fold reduction in catalytic activity.
Abolishes formation of disulfide-linked homotetramers. Abolishes the cooperative enzyme kinetics that are seen under oxidative conditions.
Decreases catalytic activity. Increases affinity for malonyl-CoA.
Does not abolish formation of disulfide-linked homotetramers. No effect on development of cooperative enzyme kinetics in response to oxidative conditions.
Malonyl-CoA decarboxylase, mitochondrial
Abolishes FYB1-dependent activation of ITGAL clustering.
Abolishes homodimerization, interaction with FYB1 and activation of the MAP kinase pathway.
Abolishes interaction with PTPRC, translocation to cell membrane upon T-cell stimulation and activation of the MAP kinase pathway. No effect on interaction with FYN or GRB2.
Impairs interaction with PTPRC. No effect on interaction with FYN or GRB2.
No effect on interaction with PTPRC and translocation to cell membrane upon T-cell stimulation. Abolishes interaction with FYN and GRB2 and activation of the MAP kinase pathway.
In MC1DN1; loss of mitochondrial respiratory complex I; altered nonsense mediated mRNA decay.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
Coiled-coil domain-containing protein 169
Mediator of RNA polymerase II transcription subunit 18
DNA-directed RNA polymerase I subunit RPA49
Diminished but persistent lysosomal targeting.
T-cell surface glycoprotein CD3 gamma chain
Fibronectin type III domain-containing protein 1
Zinc finger CCHC domain-containing protein 17
ATP-binding cassette sub-family A member 10
May be associated with type 2 diabetes obese individuals.
Decreases homodimerization. Reduces binding to PPP2R5C. Decreases protein level.
Abolishes binding to bikunin. Has no effect on transesterification reaction.
Abolishes binding to bikunin. Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling. Has no effect on transesterification reaction.
Abolishes binding to bikunin. Impairs binding to hyaluronan. Retains the ability to bind heavy chains but cannot transfer them onto hyaluronan. Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling.
Decreases binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling.
Decreases binding to heparin. Has normal binding to bikunin.
Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin and decreases the potentiation effect toward bikunin antiprotease activity; when associated with A-55 and A-69. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-55 and A-69.
Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin; when associated with A-55 and A-76. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-55 and A-76.
Decreases binding to heparin. Has normal binding to bikunin. Impairs binding to heparin; when associated with A-69 and A-76. Has no effect on CXCL8-induced neutrophil transmigration; when associated with A-69 and A-76.
Has no significant effect on hyaluronan binding to CD44 or hyaluronan-dependent lymphocyte rolling.
Impairs binding of hyaluronan to CD44. Decreases hyaluronan-dependent lymphocyte rolling.
Increases binding of hyaluronan to CD44. Has no significant effect on hyaluronan-dependent lymphocyte rolling.
Reduces the binding affinity to calcium ions. Abolishes the interaction with heavy chain ITIH1.
Tumor necrosis factor-inducible gene 6 protein
In BRENS; decreased protein abundance; associated with abnormal ciliary structure and function.
In BRENS; unknown pathological significance.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2
Ankyrin repeat, SAM and basic leucine zipper domain-containing protein 1
Loss of interaction with GOPC; when associated with A-121 and A-128.
Loss of interaction with GOPC; when associated with A-121 and A-135.
Loss of interaction with GOPC; when associated with A-128 and A-135.
In SSDA; loss of catalytic activity toward IGFBP3 and IGFBP5.
Found in a patient with THC1; unknown pathological significance.
In XLN; a constitutively activating mutation.
May be associated with risk of familial obesity.
Substantially reduced RabGAP GTPase hydrolysis activity.
Transient receptor potential cation channel subfamily M member 5
Abolishes phospholipase activity. Loss of efficient targeting to the Golgi apparatus. No effect on PI(3)P-, PI(4)P-, PI(5)P-binding.
Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-435.
Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-436.
Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-435 and A-436.
Phospholipid phosphatase-related protein type 2
115-fold more potently inhibited by the alpha-conotoxin ImI; but no change in inhibition by the alpha-conotoxin ImII.
Neuronal acetylcholine receptor subunit alpha-7
In DMJDS1; unknown pathological significance.
Phospholipid phosphatase-related protein type 5
Connector enhancer of kinase suppressor of ras 2
Short-chain dehydrogenase/reductase family 42E member 1
In CPHD4; has impaired activity on CGA, POU1F1 and TSHB promoters but exhibits normal DNA binding to the CGA pituitary glycoprotein basal element (PGBE) and interaction with the POU1F1 protein.
In CPHD4; the mutant protein is inactive in DNA binding and pituitary gene activation assays.
Ankyrin repeat and SAM domain-containing protein 1A
Decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation.
Decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation; when associated with A-450.
Decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation; when associated with A-452.
Loss of LIN28A and pre-let-7 RNA binding and loss of pre-let-7 RNA uridylylation; when associated with A-306.
Loss of LIN28A and pre-let-7 RNA binding and loss of pre-let-7 RNA uridylylation; when associated with A-309.
Loss of interaction with LIN28A and pre-let-7 RNA.
Loss of nucleotidyltransferase activity and stabilization of pre-let-7 miRNAs. Abolishes inhibition of LIRE1 retrotransposition.
Strongly decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation.
Strongly decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation; when associated with A-321.
Strongly decreased LIN28A and pre-let-7 RNA binding and pre-let-7 RNA uridylylation; when associated with A-324.
TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L
26S proteasome non-ATPase regulatory subunit 14
Abolishes ubiquitin thioesterase activity, leading to prevent maintenance of JMJD2A/KDM4A on chromatin.
All-trans retinoic acid-induced differentiation factor
Loss of dimerization; when associated with E-958.
Loss of dimerization; when associated with E-960.
Loss of dimerization; when associated with K-1305.
Loss of dimerization; when associated with K-1306.
Receptor-type tyrosine-protein phosphatase gamma
SH3 domain-binding glutamic acid-rich protein
FXYD domain-containing ion transport regulator
FXYD domain-containing ion transport regulator 5
Abolished STAT1 activation upon IFNA2 binding but no effect upon IFNG binding.
Abolishes interaction with FBXW11 and decreases ubiquitination.
Abolishes phosphorylation at this site and interaction with SHMT2.
Decreased STAT1 activation upon IFNA2 binding but no effect upon IFNG binding.
Impairs internalization in response to interferon.
Mildly reduces ubiquitination. Nearly abolishes ubiquitination and subsequent degradation; when associated with 525-R-R-526.
No effect on activation of STAT1 upon IFNA2 or IFNG binding IFNG binding.
No effect on activation of STAT1 upon IFNA2 or IFNG binding.
Reduces ubiquitination. Nearly abolishes ubiquitination and subsequent degradation; when associated with R-501.
Requires 2 nucleotide substitutions; no effect on activation of STAT1 upon IFNA2 or IFNG binding.
Abolishes DNA-dependent ATPase and nucleosome remodeling activities.
LIM and senescent cell antigen-like-containing domain protein 1
Loss of interaction with ILK and loss of localization to focal adhesion.
Impairs stimulation of phosphatase activity by actin but does not affect basal activity.
Reduces binding to YWHAB, YWHAG, YWHAQ and YWHAZ. Abolishes binding to YWHAB, YWHAG, YWHAQ and YWHAZ and increases association with F-actin; when associated with A-937.
Reduces binding to YWHAB, YWHAG, YWHAQ and YWHAZ. Abolishes binding to YWHAB, YWHAG, YWHAQ and YWHAZ and increases association with F-actin; when associated with A-978.
In some patients with early onset breast cancer.
In some patients with early onset breast cancer; requires 2 nucleotide substitutions.
Barrier-to-autointegration factor-like protein
Abolishes activation of STK11/LKB1; when associated with A-240.
Abolishes activation of STK11/LKB1; when associated with A-243.
Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus.
In FASPS2; strongly reduces kinase activity.
Displays reduced current rundown following repeated receptor activation.
Gamma-aminobutyric acid receptor subunit beta-2
In IECEE2; loss of localization to the cell membrane; retained intracellularly it affects the cell surface expression of the GABA receptor; decreased GABA receptor activity.
In IECEE2; unknown pathological significance.
Cytochrome b-c1 complex subunit 6-like, mitochondrial
Zinc finger CCCH domain-containing protein 3
Affects subcellular localization. Accumulates mainly in the soma of the neuroblastoma cells.
Does not affect subcellular localization. Distributed throughout the soma and neurites.
Found in a patient with ARSEGS; unknown pathological significance.
In ARSEGS; complete loss of tyrosine 3-monooxygenase activity.
In ARSEGS; loss of about 40% of tyrosine 3-monooxygenase activity.
In ARSEGS; loss of about 50% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa.
In ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity.
In ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; reduced affinity for L-tyrosine.
In ARSEGS; loss of over 80% of tyrosine 3-monooxygenase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa.
In ARSEGS; no effect on tyrosine 3-monooxygenase activity.
In ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine 3-monooxygenase activity.
In ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine 3-monooxygenase activity.
In ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D).
In ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and tyrosine 3-monooxygenase activity; rare mutation.
Suppresses feedback inhibition induced by dopamine. Suppresses feedback inhibition induced by dopamine; when associated with A-207.
Suppresses the decrease in tyrosine 3-monooxygenase activity induced by NEM modification. Suppresses feedback inhibition induced by dopamine; when associated with E-71.
Decreases heteromer formation with CRYAB.
Decreases phosphorylation at Ser-16; abolishes cardioprotective effects.
Increases homodimer-based self-association properties; increases chaperone activity; when associated with G-3.
Increases homodimer-based self-association properties; increases chaperone activity; when associated with G-5.
No effect on homodimer-based self-association properties; no effect on chaperone activity.
Changed glutamate-gated calcium ion channel activity characterized by accelerated response activation time and increased desensitization.
Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course.
Found in a cutaneous malignant melanoma sample.
Found in a cutaneous malignant melanoma sample; somatic mutation.
Found in a cutaneous malignant melanoma sample; somatic mutation; also found in a patient with benign epilepsy with centrotemporal spike.
Found in a patient with continuous spike-wave discharges during slow-wave sleep; also found in a patient with drug-resistant focal epilepsy; also found in a cutaneous malignant melanoma sample as somatic mutation; unknown pathological significance.
Found in a patient with neonatal onset epileptic encephalopathy; unknown pathological significance.
In FESD; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability.
In FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by affected receptor kinetics.
In FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency and decreased open probability.
In FESD; decreased protein abundance; decreased localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency.
In FESD; decreased protein abundance; decreased localization to the cell membrane; decreased glutamate-gated calcium ion channel activity characterized by drastically decreased glutamate agonist potency, decreased glycine agonist potency, reduced amplitude of current response, shortened synaptic-like response time course, decreased channel open probability and enhanced sensitivity to negative allosteric modulators.
In FESD; decreased protein abundance; decreased localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol.
In FESD; decreased protein abundance; loss of localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased glycine potency.
In FESD; decreased protein abundance; no effect on localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol.
In FESD; gain-of-function characterized by enhanced agonist potency, reduced sensitivity to endogenous negative inhibitors, prolonged synaptic-like response time course, increased single-channel mean open time and increased channel open probability.
In FESD; increase in receptor response to agonists; decrease in the actions of endogenous negative modulators; increase in channel open probability; prolonged deactivation time course.
In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by decreased glutamate potency.
In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency with delay in rise time and slower deactivation time course.
In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency.
In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency and decreased open probability.
In FESD; no effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency.
In FESD; no effect on localization to the cell membrane; loss of glutamate-gated calcium ion channel activity.
In FESD; results in reduced high-affinity zinc mediated inhibition.
In FESD; the mutant receptor has decreased calcium permeability; shows a dominant-negative effect.
In FESD; unknown pathological significance.
No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by decreased response amplitude and changed desensitization without effect on response rise time or deactivation time course.
No effect on localization to the cell membrane. Changed glutamate-gated calcium ion channel activity characterized by increased desensitization.
No effect on localization to the cell membrane; changed glutamate-gated calcium ion channel activity characterized by increased glutamate potency.
Probable disease-associated variant found in a patient with schizophrenia.
Abolished interaction with DDB1, DDA1 and RBM39 in presence of indisulam.
Decreased interaction with DDA1 and RBM39 in presence of indisulam.
Decreased interaction with DDB1, DDA1 and RBM39 in presence of indisulam.
Decreased interaction with RBM39 in presence of indisulam, without affecting interaction with DDA1 and DDB1.
In allele HA-2M; the HA-2V allele constitute the HA-2 epitope while HA-2M is not recognized by HA-2 cytotoxic T lymphocytes.
No effect on membrane localization; when associated with K-883.
No effect on membrane localization; when associated with R-885.
No effect on membrane localization; when associated with R-903.
No effect on membrane localization; when associated with R-906.
Histone-lysine N-methyltransferase PRDM9
In allele L13; Increases affinity for the DNA-binding motif 5'-GCCTCCCTAGCCACG-3'.
In allele L20; reduces affinity for the DNA-binding motif 5?-GCCTCCCTAGCCACG-3'.
In allele L9/24; significantly reduces affinity for the DNA-binding motif 5'-GCCTCCCTAGCCACG-3'.
Increases histone-lysine N-methyltransferase activity; when associated with D-374.
Increases histone-lysine N-methyltransferase activity; when associated with Y-199.
Loss of histone-lysine N-methyltransferase activity.
Variant of uncertain significance; may be a genetic risk for patients with azoospermia caused by meiotic arrest.
Bipartite nuclear localization signal; in isoform 2
Decreases specificity for CDC42; when associated with I-1376.
Decreases specificity for CDC42; when associated with L-1369.
In isoform 10, isoform 11 and isoform 12.
In isoform 2, isoform 3, isoform 7, isoform 10, isoform 11 and isoform 12.
In isoform 3, isoform 4, isoform 11 and isoform 12.
In isoform 3, isoform 5, isoform 6, isoform 7, isoform 8, isoform 9, isoform 10, isoform 12 and isoform 13.
In FSGS2; decreases calcium ion transport.
In FSGS2; decreases calcium ion transport; does not change localization at cell membrane; does not affect homodimer formation.
In FSGS2; increases calcium ion transport.
In FSGS2; increases cation channel activity; does not change plasma membrane expression; increases calcium ion transport.
In FSGS2; increases cation channel activity; does not change plasma membrane expression; significantly reduces the ratio of cell-surface to total expression; increases calcium ion transport.
In FSGS2; increases cation channel activity; does not change the outward peak current; increases significantly the inward peak current amplitude; increases calcium ion transport.
In FSGS2; unknown pathological significance.
In FSGS2; unknown pathological significance; decreases calcium ion transport.
In FSGS2; unknown pathological significance; requires 2 nucleotide substitutions; decreases calcium ion transport.
Increases calcium transport. Increases calcium ion transport.
Increases cation channel activity. Increases significantly inward and outward currents and does not show channel inactivation. Increases calcium ion transport.
No effect on RNF24-binding; when associated with A-125; A-127 and A-128.
No effect on RNF24-binding; when associated with A-125; A-127 and A-130.
No effect on RNF24-binding; when associated with A-125; A-128 and A-130.
No effect on RNF24-binding; when associated with A-127; A-128 and A-130.
Short transient receptor potential channel 6
Dramatic decrease in histone acetylation.
Found in a patient with X-linked intellectual disability; unknown pathological significance.
In MRXS33; unknown pathological significance.
In a lung bronchoalveolar carcinoma sample; somatic mutation.
In isoform 2d, isoform 2g and isoform N-TAF1.
In isoform 2g, isoform 2a, isoform 2c, isoform 2d and isoform 3.
In isoform 2g, isoform 2a, isoform 3 and isoform 4.
Reduces kinase activity; when associated with A-145; A-147; A-149; A-150 and A-152.
Reduces kinase activity; when associated with A-145; A-147; A-149; A-150 and A-154.
Reduces kinase activity; when associated with A-145; A-147; A-149; A-152 and A-154.
Reduces kinase activity; when associated with A-145; A-147; A-150; A-152 and A-154.
Reduces kinase activity; when associated with A-145; A-149; A-150; A-152 and A-154.
Reduces kinase activity; when associated with A-147; A-149; A-150; A-152 and A-154.
Reduces kinase activity; when associated with A-305; A-307; A-308 and A-309.
Reduces kinase activity; when associated with A-305; A-307; A-308 and A-310.
Reduces kinase activity; when associated with A-305; A-307; A-309 and A-310.
Reduces kinase activity; when associated with A-305; A-308; A-309 and A-310.
Reduces kinase activity; when associated with A-307; A-308; A-309 and A-310.
Transcription initiation factor TFIID subunit 1
Impairs PGE2 synthesis. Impairs PGD2 synthesis. Impairs mast cell degranulation. Impairs neurite outgrowth.
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-312)
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-89)
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-154); alternate
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-212); alternate
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-213); alternate
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-216); alternate
Found in an acute myeloid leukemia sample; somatic mutation.
Probable sodium-coupled neutral amino acid transporter 6
Loss of phosphorylation and its ability to potentiate JUN transcriptional activator activity.
Bifunctional purine biosynthesis protein ATIC
Bifunctional purine biosynthesis protein ATIC, N-terminally processed
Decreased FAICAR cyclization activity; no change in affinity to FAICAR.
Decreased affinity to FAICAR; no change in FAICAR cyclization activity.
In AICAR; loss of transformylase activity.
Proton acceptor; for AICAR formyltransferase activity
Proton donor/acceptor; for FAICAR cyclization activity
In MECD1; increased expression of keratins KRT5, KRT6, KRT14 and KRT16 and decreased expression of KRT12 in the corneal epithelium; increased expression of DDIT3/CHOP and CASP12 in the corneal epithelium indicative of up-regulation of the unfolded protein response..
In MECD1; unknown pathological significance.
Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-171 and Q-346.
Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-171 and Q-584.
Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-165; Q-346 and Q-584.
Greatly reduced acetylation and insensitive to treatment with TSA and NAM; when associated with Q-171; Q-346 and Q-584.
In FRTS3; the mutant is mistargeted to mitochondria; results in impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids across the epithelium of renal proximal tubular cells.
BAG family molecular chaperone regulator 1
Significant loss of interaction with HSPA8.
In MGCA9; unknown pathological significance.
Mitochondrial import inner membrane translocase subunit TIM50
Alleviates phosphorylation, leaves a fully active enzyme with compromised cellular resistance to ionizing radiation without affecting DNA end joining; when associated with A-2638.
Alleviates phosphorylation, leaves a fully active enzyme with compromised cellular resistance to ionizing radiation without affecting DNA end joining; when associated with A-2647.
DNA-dependent protein kinase catalytic subunit
In IMD26; shows impaired function in response to irradiation and a less severe defect in V(D)J end-joining suggesting that the missense mutation retained some functional capacity; consistent with a loss of function mutation.
In IMD26; shows increased long palindromic (P)-nucleotide stretches in the immunoglobulin coding joints indicating a defect in hairpin opening and insufficient DCLRE1C activation.
Leads to radiation sensitivity and impaired DSB joining. Gives rise to reduced phosphorylation; when associated with A-2612.
Reduced phosphorylation; when associated with A-2609.
Meiosis-specific with OB domain-containing protein
Protein kinase C and casein kinase substrate in neurons protein 3
Coiled-coil domain-containing protein 127
In CORD12, STGD4 and MCDR2; affects the interaction with actin.
Loss of acetylation; when associated with Q-225 and Q-257.
Loss of acetylation; when associated with Q-225 and Q-264.
Loss of acetylation; when associated with Q-257 and Q-264.
Loss of expression of the protein in part due to proteasomal degradation; when associated with Q-225 and Q-257.
Loss of expression of the protein in part due to proteasomal degradation; when associated with Q-225 and Q-264.
Loss of expression of the protein in part due to proteasomal degradation; when associated with Q-257 and Q-264.
Glycerol-3-phosphate acyltransferase 2, mitochondrial
Hairy/enhancer-of-split related with YRPW motif protein 2
In a patient with atrioventricular septal defects.
Abolishes kynurenine 3-monooxygenase activity.
Decreases to 30% NADPH oxidase activity.
Decreases to 50% NADPH oxidase activity.
Not glycosylted. Reduces to 80% kynurenine 3-monooxygenase activity.
Strongly decreases kynurenine 3-monooxygenase activity.
In PCH14; reduced protein levels in homozygous patient's fibroblasts compared to heterozygous or wild-type cells.
In PCH14; strongly reduced interaction with SNW1; slightly reduced protein levels compared to wild-type, after transfection in HEK293T cell line, reduced thermal stability and increased aggregation propensity in vitro; in transgenic knockin mice, produces a pontocerebellar hypoplasia-like phenotype.
In PCH14; strongly reduced interaction with SNW1; strongly reduced protein levels in homozygous patient's fibroblasts compared to heterozygous or wild-type cells; in transgenic knockin mice, produces a pontocerebellar hypoplasia-like phenotype.
In PCH14; unknown pathological significance.
In PCH14; unknown pathological significance; reduced interaction with SNW1; no effect on protein expression level, but shows reduced thermal stability and increased aggregation propensity in vitro.
In PCH14; unknown pathological significance; strongly reduced protein levels compared to wild-type after transfection in HEK293T cell line.
Loss of isomerase activity. Can rescue splicing defects when transfected in knockout cells.
Peptidyl-prolyl cis-trans isomerase-like 1
In HLASA; decreased leucine-tRNA ligase activity.
In PRLTS4 and HLASA; reduced activity; decreased leucine-tRNA ligase activity.
In PRLTS4; unknown pathological significance; the mutant is functional in a yeast complementation assay.
Loss of OCRL-binding. Drastically reduces membrane targeting.
In MMIHS3; markedly reduced LMOD1 protein levels in homozygous patient cells.
Dynein assembly factor with WDR repeat domains 1
Loss of cholesterol 25-hydroxylase activity. Loss of inhibition of infection by SARS-COV-2.
Carcinoembryonic antigen-related cell adhesion molecule 16
In DFNA4B; impairs homooligomerization of the protein; decreases secretion of the protein.
In AIFEC; results in a gain of function mutation with constitutive activation of caspase-1.
In FCAS4; the mutation increases oligomerization of the NLRC4 protein; results in hyperactivation of caspase-1 with an increase in IL1B protein secretion.
NLR family CARD domain-containing protein 4
Disrupts localization to mitotic spindle and impairs recruitment of clathrin to mitotic spindle.
Impairs localization to mitotic spindle.
Transforming acidic coiled-coil-containing protein 3
Receptor-type tyrosine-protein phosphatase R
Leucine-rich repeat-containing protein 25
28S ribosomal protein S35, mitochondrial
Myristoylated alanine-rich C-kinase substrate
Leucine-rich repeat-containing protein 4
Ankyrin repeat and SAM domain-containing protein 3
Decreased homooligomerization. Decreased interaction with ANKS6.
Decreased homooligomerization. No effect on interaction with ANKS6.
Abolishes targeting to endosomes and results in relocalization to the cell membrane.
Decreases the interaction with MHCII and peptide exchange.
HLA class II histocompatibility antigen, DM beta chain
In allele DMB*01:02 and allele DMB*01:06.
In allele DMB*01:04 and allele DMB*01:05.
Increases the interaction with MHCII and peptide exchange; when associated with N-49.
Increases the interaction with MHCII and peptide exchange; when associated with Q-65.
Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-32.
Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-35.
Loss of nitrosylation, and loss of S-nitrosylating activity towards CASP3. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-69.
No effect on reducing activity, interaction with APEX1 and on S-nitrosylation of C-73. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-73.
Retains its reducing activity. Retains interaction with APEX1 and transcription activation; when associated with S-69 and S-73.
Strongly reduced S-nitrosylation of CASP3.
Strongly reduced interaction with CASP3; when associated with A-70.
Strongly reduced interaction with CASP3; when associated with A-72.
In XLRS1; decreases protein stability; does not abrogate oligomerization or secretion.
In XLRS1; loss of octamerization; no effect on secretion.
In XLRS1; loss of secretion into the extracellular space; may impair protein folding.
In XLRS1; no effect on oligomerization; no effect on protein stability.
Extracellular superoxide dismutase [Cu-Zn]
N-linked (Glc) (glycation) lysine; in vitro
RNA polymerase II elongation factor ELL2
Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-110 and A-123.
Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-110 and A-127.
Does not affect the binding of SEMG1 or LTF. Does not affect the binding of SEMG1; when associated with A-123 and A-127.
Reduces the binding to SEMG1 by 68% and to LTF by 73%.
Ribosome biogenesis protein SLX9 homolog
In ADTKD4; affects ER translocation and processing of nascent preprorenin, resulting in abolished prorenin and renin biosynthesis and secretion.
HLA class II histocompatibility antigen, DR beta 5 chain
In allele DRB5*01:02, allele DRB5*01:03, allele DRB5*01:05, allele DRB5*01:14, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05.
In allele DRB5*01:02, allele DRB5*01:03, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05.
In allele DRB5*01:04; requires 2 nucleotide substitutions.
In allele DRB5*01:06, allele DRB5*01:07, allele DRB5*01:11, allele DRB5*02:02 and allele DRB5*02:03.
In allele DRB5*01:06, allele DRB5*01:11, allele DRB5*02:02, allele DRB5*02:03 and allele DRB5*02:04; requires 2 nucleotide substitutions.
In allele DRB5*01:06, allele DRB5*01:11, allele DRB5*02:02, allele DRB5*02:03, allele DRB5*02:04 and allele DRB5*02:05; requires 2 nucleotide substitutions.
In allele DRB5*01:06, allele DRB5*02:02, allele DRB5*02:04 and allele DRB5*02:05.
In allele DRB5*01:12; requires 2 nucleotide substitutions.
In allele DRB5*02:02, allele DRB5*02:04 and allele DRB5*02:05.
In allele DRB5*02:02; requires 2 nucleotide substitutions.
[Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 2, mitochondrial
ATPase family AAA domain-containing protein 3A
In PHRINL; decreased protein levels in patient cells.
Loss of S100B-binding; when associated with S-341.
Loss of S100B-binding; when associated with S-345.
No effect on homooligomerization. Immediate fragmentation of the mitochondrial network.
Tubulin epsilon and delta complex protein 1
Loss of interaction with human HIV-1 integrase and POGZ; reduced interaction with CDCA7L.
Loss of interaction with human HIV-1 integrase; no effect on interaction with CDCA7L and POGZ.
Loss of interaction with human HIV-1 integrase; no effect on interaction with KMT2A.
Loss of interaction with human HIV-1 integrase; reduced interaction with POGZ and CDCA7L.
Reduced interaction with KMT2A. Significant loss of interaction with KMT2A; when associated with A-368.
Reduced interaction with KMT2A. Significant loss of interaction with KMT2A; when associated with D-407.
Reduced interaction with POGZ, CDCA7L and human HIV-1 integrase.
Reduced interaction with human HIV-1 integrase; no effect on interaction with POGZ and CDCA7L.
Significant loss of interaction with KMT2A; when associated with D-404.
Significant loss of interaction with KMT2A; when associated with D-405.
In AH5; 10% 17alpha-hydroxylase activity and 13% 17,20-lyase activity.
In AH5; 10% 17alpha-hydroxylase and 17,20-lyase activities.
In AH5; 25% of both 17alpha-hydroxylase and 17,20-lyase activities.
In AH5; 30% 17alpha-hydroxylase activity and 29% 17,20-lyase activity.
In AH5; 38% 17alpha-hydroxylase activity and 33% 17,20-lyase activity.
In AH5; ablates both 17,20-lyase activity and 17alpha-hydroxylase activity; loss of heme-binding and loss of phosphorylation.
In AH5; complete loss of both 17alpha-hydroxylase and 17,20-lyase activities.
In AH5; selectively ablates 17,20-lyase activity, while preserving most 17alpha-hydroxylase activity.
Increases the affinity for progesterone, resulting in preferential hydroxylation of progesterone at C17 over C16; increases the catalytic efficiency in the 17,20 lyase reaction.
Steroid 17-alpha-hydroxylase/17,20 lyase
5-fold activation and 18-fold activation; when associated with D-473.
7-fold activation and 25-fold activation; when associated with D-308.
Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
In PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain.
No effect on membrane localization. Loss of membrane localization; when associated with Q-20.
Phosphoserine; by IKKE, MTOR and TBK1; alternate
Phosphothreonine; by IKKE, PDPK1 and TBK1
RAC-alpha serine/threonine-protein kinase
Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305.
Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312.
Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473.
Slight increase of phosphorylation at T-308 and S-473.
Substantial reduction of phosphorylation at T-308 and S-473, loss of AKT activation, and loss of binding to PIP3 as well as IGF1-induced membrane recruitment.
Substantial reduction of phosphorylation at T-308 and S-473, reduced AKT activation, and reduced binding to PIP3 as well as IGF1-induced membrane recruitment. Loss of membrane localization; when associated with K-17.
Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation as well as IGF1-induced membrane recruitment. Decrease in ubiquitination and phosphorylation at T-308 as well as impaired association with the membrane; when associated with K-17.
Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation, loss of binding to PIP3 as well as IGF1-induced membrane recruitment.
In SDDHD; decreased of transketolase activity.
In IGAN3; no effect on protein expression; negatively regulates ERK1 and ERK2 cascade.
Inhibits cleavage by the prolyl endopeptidase FAP.
In isoform 4, isoform 5, isoform 6 and isoform 7.
Xin actin-binding repeat-containing protein 2
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 6
In PKRD; Amish; no conformational change.
In PKRD; Complete loss in the responsiveness to fructose 1,6-bisphosphate, FBP.
In PKRD; Mantova; almost complete inactivation.
In PKRD; Tjaereborg; unstability of the protein and decrease in catalytic activity.
In PKRD; Tokyo/Beirut; no conformational change.
Arf-GAP domain and FG repeat-containing protein 1
15-20 fold defects in kinase activity; when associated with A-484.
15-20 fold defects in kinase activity; when associated with A-485.
Exerts a protective effect in heart failure and ischemia.
No detectable plasma membrane localization; when associated with A-550; A-551; and A-554.
No detectable plasma membrane localization; when associated with A-550; A-551; and A-555.
No detectable plasma membrane localization; when associated with A-550; A-554; and A-555.
No detectable plasma membrane localization; when associated with A-551; A-554; and A-555.
Nuclear exclusion; when associated with A-388; A-389; A-391 and A-393.
Nuclear exclusion; when associated with A-388; A-389; A-391 and A-394.
Nuclear exclusion; when associated with A-388; A-389; A-393 and A-394.
Nuclear exclusion; when associated with A-388; A-391; A-393 and A-394.
Nuclear exclusion; when associated with A-389; A-391; A-393 and A-394.
Pleckstrin homology domain-containing family M member 3
Found in a patient with intellectual disability, frontal epilepsy and mild facial dysmorphism.
Rap guanine nucleotide exchange factor 1
Acts as a dominant negative GPCR and inhibits S1P-induced Rac activation, chemotaxis, and angiogenesis.
Drastically reduced affinity for sphingosine 1-phosphate.
Impairs sphingosine 1-phosphate binding and signaling.
Slight activation of the receptor at maximal ligand concentration.
In DFNB115; unknown pathological significance.
Loss of function; does not rescue the cardia bifida phenotype in the morpholino knockdown in zebrafish.
Sphingosine-1-phosphate transporter SPNS2
Found in a child with sporadic epilepsy; unknown pathological significance.
Vimentin-type intermediate filament-associated coiled-coil protein
Does not restore any protein tyrosine phosphatase activity.
Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2
In A1 mutant; abolished ATP-binding; decreased interaction with PEX6; decreased localization to peroxisomal membranes.
In A2 mutant; abolished ATP-binding; decreased interaction with PEX6; decreased localization to peroxisomal membranes.
In B1 mutant; abolished ATP hydrolysis; decreased interaction with PEX6; decreased localization to peroxisomal membranes.
In B2 mutant; abolished ATP hydrolysis; does not affect interaction with PEX6; does not affect localization to peroxisomal membranes.
In HMLR1; results in mild functional decrease in peroxisome biogenesis.
In PBD1A and PBD1B; decreased binding to PEX6; impaired protein import into peroxisomes.
In PBD1A; impaired protein import into peroxisomes.
Ankyrin repeat domain-containing protein 30A
Developmentally-regulated GTP-binding protein 2
Impairs JMJD7-mediated hydroxylation and ribonucleic acid binding.
Abolished ability to activate IRF3 and induce the production of type I interferon.
Abolished ability to induce autophagy. Abolished interaction with SEC24C.
Abolished ability to induce the production of type I interferon.
Abolished cGAMP-binding. Abolished ability to induce autophagy.
Abolished inhibition by small-molecule H-151; abolished palmitoylation.
Abolished translocation from the endoplasmic reticulum in response to cGAMP-binding. Reduced phosphorylation by TBK1.
Abolishes the endoplasmic reticulum location.
Abolishes ubiquitination, homodimerization and subsequent production of IFN-beta.
Activated by both 2'-3' linked cGAMP and 3'-3' linked cGAMP.
Constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Decreased phosphorylation by TBK1, leading to reduced ability to activate IRF3.
Does not affect ability to activate IRF3.
Does not affect ability to activate IRF3. Abolished ability to induce the production of type I interferon.
Does not affect amount of ubiquitination.
In SAVI; constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Induces a decrease in phosphorylation by TBK1.
Induces a decrease in phosphorylation by TBK1. Abolished ability to activate IRF3.
Partially constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Phosphomimetic mutant; retains some ability to activate IRF3. It probably incompletely mimics phosphorylation.
Probable disease-associated variant found in a 9-month-old patient who died following a fever and severe neck abscess without indication of any severe bacterial infection; may affect splicing; constitutively active mutant that promotes the production of type I interferon in absence of cyclic dinucleotide ligand; localizes to the perinuclear region in absence of cyclic dinucleotide ligand.
Renders the enzyme senstive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway.
Renders the enzyme senstive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway; when associated with A-162.
Slight decrease in c-di-GMP-binding. Renders the enzyme senstive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway. Renders the enzyme senstive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug; when associated with I-266.
Slightly affects ability to induce the production of type I interferon.
Strong decrease in c-di-GMP and cGAMP-binding.
Strong decrease in cGAMP-binding without affecting interaction with TBK1. Abolished ability to induce autophagy.
Decreased EIF4A3-binding; when associated with A-331.
Decreased EIF4A3-binding; when associated with A-334.
No effect on EIF4A3 incorporation into EJCs.
Ribosomal L1 domain-containing protein 1
Synaptonemal complex central element protein 2
CDK2-associated and cullin domain-containing protein 1
In isoform L-VEGF165, isoform L-VEGF121, isoform L-VEGF189, isoform L-VEGF206, isoform 15, isoform 16, isoform 17 and isoform 18.
In isoform VEGF121 and isoform L-VEGF121.
In isoform VEGF148, isoform VEGF165, isoform VEGF165B and isoform L-VEGF165.
In isoform VEGF189 and isoform L-VEGF189.
Abolishes carbohydrate binding for the trisaccharide Gal(beta1-3/4)GlcNAc(beta1-2)Man.
Significantly impairs carbohydrate binding for the trisaccharide Gal(beta1-3/4)GlcNAc(beta1-2)Man.
Decreased ubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex.
Does not affect ubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex.
In DIAR10; the protein is not expressed in the patient biopsy tissues.
Associated with increased risk for thiopurines toxicity; decreased thermostability; decreased diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP.
Associated with increased risk for thiopurines toxicity; decreased thermostability; loss of diphosphatase activity towards 6-thio-dGTP and 6-thio-GTP.
Nucleotide triphosphate diphosphatase NUDT15
Loss of protection from cell death during oxidative stress; when associated with A-116.
Loss of protection from cell death during oxidative stress; when associated with A-203.
Decreases interaction with INPP5D/SHIP-1; when associated A-38.
Decreases interaction with INPP5D/SHIP-1; when associated A-6.
Has little impact on affinity for HLA-E.
Has no impact on the affinity for HLA-E.
Immunoreceptor tyrosine-based inhibition motif (ITIM)
Impairs phosphorylation, interaction with INPP5D/SHIP-1 and NK cell functional inhibition; when associated F-40.
Impairs phosphorylation, interaction with INPP5D/SHIP-1 and NK cell functional inhibition; when associated F-8.
NKG2-A/NKG2-B type II integral membrane protein
Abolishes ability to mediate necroptosis. Partial loss of kinase activity. No loss of PELI1-mediated degradation.
Abolishes kinase activity and ability to mediate necroptosis.
Abolishes kinase activity. Loss of PGAM5- and MLKL-binding. No effect on RIPK1-binding. Loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of STUB1-mediated ubiquitination.
Abolishes kinase activity. Loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of interaction with STUB1 and STUB1-mediated ubiquitination. No loss of interaction with RIPK1. Loss of ability to mediate TNF-induced necroptosis. Loss of autophosphorylation at Ser-227.
Loss of PELI1-mediated ubiquitination. No loss of interaction with PELI1.
Loss of interaction with PELI1 and PELI1-mediated ubiquitination.
No loss of interaction with PELI1 and PELI1-mediated ubiquitination. No loss of interaction with RIPK1 and MLKL.
Receptor-interacting serine/threonine-protein kinase 3
No effect on dimerization. Loss of dimerization and of enzyme activity; when associated with 294-AAAA-297.
Reduced dimerization. Loss of dimerization and of enzyme activity; when associated with 259-AAA-261.
Zinc finger and BTB domain-containing protein 6
5 times reduced N-alpha-acetyltransferase activity.
Abolished N-alpha-acetyltransferase activity.
Does not affect N-alpha-acetyltransferase activity.
Reduced N-alpha-acetyltransferase activity.
Slightly reduced N-alpha-acetyltransferase activity.
Strongly reduced N-alpha-acetyltransferase activity.
Insulin-like growth factor-binding protein 7
Neuroblastoma breakpoint family member 1
Abolishes automethylation. Impairs the methyltransferase activity toward RELA and PAK4; when associated with Arg-39.
Abolishes methyltransferase activity. Greatly decreases the stability of monomeric, homodimeric and homotrimeric structures.
Decreases the methyltransferase activity toward RELA.
Greatly decreases automethylation. Impairs the methyltransferase activity toward RELA and PAK4; when associated with Arg-179.
Has little effect on automethylation level.
Impairs the methyltransferase activity toward RELA.
Abolishes S-acylation; when associated with S-150.
Abolishes S-acylation; when associated with S-151.
Cilia- and flagella-associated protein 299
Corticotropin-releasing factor receptor 2
Abolished phosphorylation at Tyr-232 by isoform 1 of CHKA (CHKalpha2).
Leucine-rich repeat-containing protein 74A
Pleckstrin homology-like domain family A member 3
Zinc finger CCHC domain-containing protein 13
Cytochrome c oxidase subunit 4 isoform 2, mitochondrial
In EPIDACH; expression in patient fibroblasts is reduced to 25% of control values in normoxic conditions; the mutant protein shows an impaired response to hypoxia.
Non-receptor tyrosine-protein kinase TNK1
Vacuolar protein sorting-associated protein 18 homolog
Nuclear envelope integral membrane protein 2
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3
Interleukin-1 receptor accessory protein
Guanine nucleotide-binding protein G(o) subunit alpha
In DEE17; loss of GTP binding; decreased interaction with RGS19; decreased interaction with heterodimers formed by GNB1 and GNG3; strongly decreased localization to cell membrane.
In DEE17; somatic mosaic mutation; the mutant protein has some abnormal cytoplasmic localization.
In DEE17; the mutant protein accumulates in the cytoplasmic compartment; increased basal calcium-current density compared to wild-type.
In DEE17; the mutant protein has some abnormal cytoplasmic localization.
In DEE17; the mutant protein localizes normally to the cell periphery.
Probable disease-associated variant found in a patient with intractable early-onset epilepsy.
Probable disease-associated variant found in a patient with intractable early-onset epilepsy; loss of GTP binding; decreased interaction with RGS19; decreased interaction with heterodimers formed by GNB1 and GNG3; strongly decreased localization to cell membrane.
Inactive peptidyl-prolyl cis-trans isomerase FKBP6
Cleavage and polyadenylation specificity factor subunit 3
Does not inhibit histone 3'-end processing.
In NEDMHS; unknown pathological significance.
Reduced sumoylation; when associated with R-462 and R-465.
Reduced sumoylation; when associated with R-462 and R-545.
Reduced sumoylation; when associated with R-465 and R-545.
Spermatogenesis-associated protein 19, mitochondrial
Abolishes proteolytic cleavage by S2P; when associated with A-392.
Abolishes proteolytic cleavage by S2P; when associated with A-395.
Cyclic AMP-responsive element-binding protein 3-like protein 1
Processed cyclic AMP-responsive element-binding protein 3-like protein 1
Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma
In SDS1; strongly reduced release of EIF6 from pre-60S ribosome subunits.
In SDS1; unknown pathological significance.
Strongly reduced release of EIF6 from pre-60S ribosome subunits.
In PSS3; results in decreased enzyme activity; the mutant protein shows reduced glycosylation.
Accumulates predominantly in intracellular compartments with only a small fraction at the plasma membrane and inhibits partially the efflux activity for PC.
Does not inhibit efflux activity for PC.
Found in patients with cholangitis; unknown pathological significance.
Found in patients with gallbladder and cholestasis; unknown pathological significance.
In GBD1; loss of phosphatidylcholine transporter activity; does not alter plasma membrane location.
In GBD1; partly retained intracellularly; reduces efflux activity for PC in a phosphorylation-dependent manner.
In GBD1; reduced phosphatidylcholine transporter activity; does not alter plasma membrane location.
In GBD1; reduces efflux activity for PC in a phosphorylation-dependent manner.
In GBD1; requires 2 nucleotide substitutions.
In GBD1; severely reduced phosphatidylcholine transporter activity; does not alter plasma membrane location.
In GBD1; unknown pathological significance; moderate decrease of phosphatidylcholine transporter activity; does not alter plasma membrane location.
In ICP3, GBD1 and PFIC3; unknown pathological significance; does not alter plasma membrane location; does not inhibit efflux activity for PC.
In ICP3; disruption of protein trafficking with subsequent lack of functional protein at the cell surface.
In PFIC3 and GBD1; does not alter plasma membrane location; inhibits efflux activity for PC.
In PFIC3; alters efflux activity for PC.
In PFIC3; does not alter cytoplasmic and cell membrane location; inhibits efflux activity for PC and cholesterol.
In PFIC3; greatly reduced expression; alters efflux activity for PC.
In PFIC3; reduced phosphatidylcholine transporter activity; does not alter plasma membrane location.
In PFIC3; retained in the reticulum endoplasmic; greatly reduced expression.
In a heterozygous patient with amoxicillin/clavulanic acid-induced cholestasis.
In a heterozygous patient with risperidone-induced cholestasis.
Inhibits efflux activity for PC and cholesterol, but does not alter glycosylation and surface expression in the presence of taurocholate.
Loss of floppase activity. Strongly reduce the ATPase activity.
Reduces efflux activity for PC. Does not alter apical membrane location.
Requires 2 nucleotide substitutions; found in patients with cholangitis; unknown pathological significance.
Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and Q-989.
Significantly reduces phosphatidylcholine floppase activity; when associated with M-985 and V-990.
Significantly reduces phosphatidylcholine floppase activity; when associated with Q-989 and V-990.
Loss of phosphorylation implicated in interaction with PTPN11. Loss of interaction with PTPN11, PTPN6 and INPPL1.
No change of phosphorylation implicated in interaction with PTPN11. Loss of interaction with INPPD5, INPPL1 and GRB2.
Abrogates both transcriptional activation and repression by MORF4L2.
Disruption of MBD2-binding, loss of enhancement of MBD2-mediated repression and loss of speckled nuclear localization.
Armadillo-like helical domain-containing protein 2
In 10% of the population; abolishes flagellin signaling; associated with resistance to SLEB1.
Highly reduces ATPase activity induced by TOR1AIP2.
Loss of ATPase activity. Produces sinusoidal endoplasmic reticulum structures where it accumulates. Highly enhances interaction with TOR1AIP2. Localizes in the nuclear envelope.
Abolishes enzyme activity with phosphatidylinositol 3-phosphate. Reduces activity with phosphatidylinositol (3,5)-bisphosphate.
Loss of interaction with HSP70 and loss of the ability to promote ATXN3 proteasomal degradation.
Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-222 and A-262.
Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-222 and A-265.
Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-219; A-262 and A-265.
Loss of interaction with polyubiquitin chains, loss of interaction with PSMA3, and loss of the ability to protect ATXN3 from proteasomal degradation; when associated with A-222; A-262 and A-265.
Loss of localization to the endoplasmic reticulum and relocalization to cytoplasm and nucleus.
No effect on localization to the endoplasmic reticulum membrane.
Probable loss of interaction with HSP70 and loss of the ability to reduce PRKN aggregation.
Reduced affinity for heparin. Reduces homodimerization.
Strongly reduced affinity for heparin. Strongly reduced homodimerization.
Centriolar and ciliogenesis-associated protein HYLS1
In HLS1; altered subcellular localization, becomes localized to nuclear structures.
Found in a renal cell carcinoma case; somatic mutation.
Higher frequency in West Africans than in individuals of European ancestry; occurs with variants F-2153 and V-2984 only in individuals of European ancestry.
Higher frequency in West Africans than in individuals of European ancestry; occurs with variants V-2984 and G-3002 only in individuals of European ancestry.
In IGS1; decreases strongly the CBLIF binding affinity.
In IGS1; unknown pathological significance; results in intracellular retention of the mutant protein.
In PROCHOB; unknown pathological significance.
In a breast cancer sample; somatic mutation; may be associated with albuminuria and slightly increased glomerular filtration rate.
May be associated with albuminuria and slightly increased glomerular filtration rate.
Not found in West Africans; occurs with variants F-2153 and G-3002 only in individuals of European ancestry; associated with albuminuria in individuals of European ancestry and African Americans, both with and without diabetes; may be associated with increased risk of developing persistent microalbuminuria in individuals with type I diabetes.
Eukaryotic peptide chain release factor GTP-binding subunit ERF3B
Impairs interaction with UPF1 and PABPC1; when associated with A-55, K-56 and A-59.
Impairs interaction with UPF1 and PABPC1; when associated with K-52, A-55 and K-56.
Impairs interaction with UPF1 and PABPC1; when associated with K-52, K-56 and A-59.
Impairs interaction with UPF1 and PABPC1; when associated with K52, A-55, and A-59.
Putative phospholipase B-like 2 32 kDa form
Putative phospholipase B-like 2 45 kDa form
Abolishes phosphorylation by ROCK2; when associated with D-445.
Abolishes phosphorylation by ROCK2; when associated with D-480.
Coiled-coil domain-containing protein 178
DNA-directed RNA polymerases I, II, and III subunit RPABC2
Baculoviral IAP repeat-containing protein 2
Found in a patient with developmental delay/intellectual disability, neuromuscular and psychiatric symptoms; unknown pathological significance.
Found in two patients with developmental delay/intellectual disability, neuromuscular and psychiatric symptoms; unknown pathological significance.
Coiled-coil domain-containing protein 150
(Microbial infection) O-acetylthreonine; by Yersinia YopJ; alternate
Constitutive activation according to PubMed:8622669, but not to PubMed:8621675.
Dual specificity mitogen-activated protein kinase kinase 6
Abolishes localization to mitochondrion outer membrane.
Does not affect localization to mitochondrion outer membrane.
Rigor-like phenotype due to disruption of ATP-binding. Does not affect localization to mitochondrion.
Impairs SRA-mediated repression; when associated with 24-A-A-25.
Impairs SRA-mediated repression; when associated with A-62.
Impairs corepressor activity; when associated with 13-A-A-14.
Impairs corepressor activity; when associated with A-7.
SRA stem-loop-interacting RNA-binding protein, mitochondrial
In CDAN1B; no effect on gene expression and protein level; impaired erythroid cell differentiation; no effect on nuclear and cytoplasmic location.
In CDAN1B; reduced gene expression and protein level; impaired erythroid cell differentiation; increased S-phase of the cell-cycle; no effect on nuclear and cytoplasmic location.
In CDAN1B; unknown pathological significance.
In PCH2F; Almost complete loss of tRNA-intron endonuclease activity in vitro.
In PCH2F; Almost complete loss of tRNA-intron endonuclease activity in vitro; may affect protein levels.
tRNA-splicing endonuclease subunit Sen15
Seems to be associated with hyperandrogenism, polycystic ovary syndrome (PCOS) and systemic lupus erythematosus.
Tumor necrosis factor receptor superfamily member 1b, membrane form
Abolishes phosphorylation. Loss of binding YWHAS and YWHAZ. Localizes to the nucleus. No effect on kinase activity.
In CHDSKM; increases kinase activity; no effect on protein levels.
In MC1DN26; loss of function in complex I assembly; accumulation of several low and high molecular weight assembly intermediates is observed in patient fibroblasts.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial
Acidic leucine-rich nuclear phosphoprotein 32 family member E
In ANP32E-m1; abolished ability to interact with the H2A.Z/H2AZ1-H2B dimer.
In ANP32E-m2; abolished ability to interact with the H2A.Z/H2AZ1-H2B dimer.
Transcription elongation factor A protein 1
Cyclic AMP-dependent transcription factor ATF-5
Highly increases protein levels. No effect on protein stability enhanced by IL1B.
Increases protein levels. No effect on protein stability enhanced by IL1B.
No effect on protein levels. No effect on protein stability enhanced by IL1B.
Not phosphorylated; when associated with 92-A--A-94 and A-126.
Not phosphorylated; when associated with 92-A--A-94 and A-190.
Not phosphorylated; when associated with A-126 and A-190.
Golgin subfamily A member 6-like protein 1
Found in a patient with Joubert syndrome also carrying 2 mutations in MKS1 gene, a deletion in intron 15 and a missense mutation 'C-80'; unknown pathological significance.
Decreased transcriptional activation in response to type I interferon stimulation.
Decreased transcriptional activation in response to type I interferon stimulation. Decreased anti-viral immunity.
Does not affect transcriptional activation in response to type I interferon stimulation; does not affect anti-viral immunity.
Loss of transcriptional activation in response to type I interferon stimulation. Impaired anti-viral immunity.
In MLD-SAPB; juvenile; affects glycosylation at N-215.
In MLD-SAPB; reduces the intracellular activity of the protein significantly.
In PARK24; associated with disease susceptibility; affects the intracellular trafficking, resulting in endoplasmic reticulum retention; affects the intracellular trafficking, resulting in endoplasmic reticulum retention; cells carrying this variant show accumulation of autophagic vacuoles, impaired autophagic flux and alpha-synuclein/SNCA aggregation.
In PARK24; associated with disease susceptibility; affects the intracellular trafficking, resulting in endoplasmic reticulum retention; cells carrying this variant show accumulation of autophagic vacuoles, impaired autophagic flux and alpha-synuclein/SNCA aggregation.
Strongly decreases stimulation of cerebroside sulfate hydrolysis.
As a heterodimer with RXRA, abolishes transcriptional repression on DR1 and reduces transcriptional activation on DR5.
As a heterodimer with RXRA, abolishes transcriptional repression on DR1, reduces transcriptional activation on DR5 and binding affinity for DR1 and DR5 DNA elements.
As a heterodimer with RXRA, reduces binding affinity for DR5 DNA element and no change in binding to DR1. Reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5; when associated with E-365 and E-367. Reduces binding affinity for DR1 and DR5 DNA elements; when associated with E-120.
As a heterodimer with RXRA, reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5. Reduces binding affinity for DR1 and DR5 DNA elements; when associated with E-366.
As a heterodimer with RXRA, reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5. Reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5; when associated with E-365 and E-366.
As a heterodimer with RXRA, reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5. Reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5; when associated with E-366 and E-367.
Greatly reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with I-222 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and S-232.
In MCOPS12; increased transcriptional response to retinoic acid ligands.
In MCOPS12; increases transcriptional response to retinoic acid.
No effect on transcriptional activation in the absence of hormone.
Reduced transcriptional activation in the absence of hormone. Even greater reduction in transcriptional activation in the absence of hormone; when associated with D-223 or S-232. Great reduction in transcriptional activation in the absence of hormone; when associated with D-223 and S-232.
Reduced transcriptional activation in the absence of hormone. Some further reduction of transcriptional activity in the absence of hormone; when associated with I-222 or D-223. Great reduction in transcriptional activation in the absence of hormone; when associated with I-222 and D-223.
Reduces transcriptional repression on DR1 and reduced transcriptional activation on DR5; when associated with V-123 and E-369.
Reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5; when associated with E-369 and E-370.
Reduces transcriptional repression on DR1 and reduces transcriptional activation on DR5; when associated with V-123 and E-370.
Hematopoietic lineage cell-specific protein
Impairs phosphorylation by PLK4 and enhances ubiquitination of SASS6.
In CDG2T; loss of ApoC-III glycosylation.
In CDG2T; loss-of-funtion variant resulting in lack of ApoC-III and IgA1 glycosylation.
In CDG2T; loss-of-funtion variant resulting in lack of ApoC-III glycosylation; b.
Likely benign variant; does not affect ApoC-III glycosylation.
Polypeptide N-acetylgalactosaminyltransferase
Polypeptide N-acetylgalactosaminyltransferase 2
Polypeptide N-acetylgalactosaminyltransferase 2 soluble form
In LS; decrease in succinate dehydrogenase activity.
In MC2DN1; unknown pathological significance.
Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
In IMD70; uncertain pathological significance; strong decrease in protein expression.
Significant inhibition of interaction with AHR; partial decrease of AHR signaling induced by IVNS1ABP.
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like
Found in a patient with intellectual disability, no speech, facial and limbs dysmorphisms.
Produces non-cleavable protein which remains on centrosomes in late mitosis until its levels eventually drop in cells undergoing cytokinesis.
Stabilizes the C-terminal fragment produced by cleavage.
Found in a patient with progressive myoclonus epilepsy and developmental delay; unknown pathological significance.
In CASVDD; impaired regulation of current density and inactivation kinetics of N- and L-type calcium channels.
In CASVDD; unknown pathological significance.
Interchain (between alpha-2-2 and delta-2 chains)
Voltage-dependent calcium channel subunit alpha-2-2
Voltage-dependent calcium channel subunit alpha-2/delta-2
Voltage-dependent calcium channel subunit delta-2
Abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with A-55 and A-59.
Abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with A-55 and A-62.
Abrogates transcriptional activity and interaction with transactivation inhibition domain; when associated with A-59 and A-62.
In ADULT syndrome; confers novel transcription activation capacity on isoform 6.
In EEC3 and RHS; does not decrease the transcriptional activity of the isoform 5 on a TP53 reporter system but disrupts the dominant-negative activity of isoform 2 and isoform 5 on the transcriptional activity of TP53.
In EEC3; abolishes transcription activation.
In isoform 2, isoform 4, isoform 6, isoform 8, isoform 10 and isoform 12.
Increases methylation activity. Higher affinity for mono-methylated peptide than wild-type.
N-terminal Xaa-Pro-Lys N-methyltransferase 2
Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial
T-cell acute lymphocytic leukemia protein 2
MPV17 mitochondrial inner membrane protein like 2
Proline/serine-rich coiled-coil protein 1
Loss of phosphorylation. Reduced stimulation of CDK1 activity.
Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-481.
Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-484.
Abolishes chromosome-condensation activity; when associated with S-392.
Abolishes chromosome-condensation activity; when associated with S-395.
No effect on activity to regulate DNA replication and on condensin complex recruitment.
No nuclear localization; when associated with 304-N-S-305.
No nuclear localization; when associated with S-290.
Ubiquitin carboxyl-terminal hydrolase 42
General transcription factor IIH subunit 2
Reconstituted TFIIH complex lacks p62 and has no transcriptional activity.
Bridge-like lipid transfer protein family member 1
In ALKKUCS; unknown pathological significance.
RNA pseudouridylate synthase domain-containing protein 1
Putative sodium-coupled neutral amino acid transporter 11
Abolishes DNA-binding to the CDK1 promoter; when associated with Y-525.
Abolishes DNA-binding to the CDK1 promoter; when associated with Y-527.
Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2
Eukaryotic translation initiation factor 1A, Y-chromosomal
Constitutive mitochondrial location. Enhanced fiber formation with humanin.
In a Burkitt lymphoma; loss of homodimerization.
In a T-cell acute lymphoblastic leukemia cell line; loss of heterodimerization with Bcl-2 or Bcl-X(L).
Reduces interaction with BCL2L11, homooligomerization and triggering of apoptosis.
Strongly reduced interaction with MCL1, BCL2, BCL2L1 and BCL2L2. No effect on cytochrome c release and subsequent apoptosis triggered by etoposide.
Putative ATP-dependent RNA helicase DHX57
In BLS2; mild immunodeficiency; has residual MHC class II trans activation activity.
Strongly reduces GTP-binding and abolishes transactivation at MHC promoters.
28S ribosomal protein S21, mitochondrial
ER degradation-enhancing alpha-mannosidase-like protein 3
In CDG2V; unknown pathological significance.
In IMD13; impairs interaction with LCK; impairs LCK activation; induces LCK mislocalization.
Loss of phosphorylation; when associated with A-37 and A-39.
Loss of phosphorylation; when associated with A-37 and A-41.
Loss of phosphorylation; when associated with A-39 and A-41.
EP300-interacting inhibitor of differentiation 2B
Signal recognition particle 9 kDa protein
Biogenesis of lysosome-related organelles complex 1 subunit 3
B-cell antigen receptor complex-associated protein alpha chain
Increased phosphorylation of Y-188; when associated with A-197 and A-203.
Increased phosphorylation of Y-188; when associated with A-197 and V-209.
Increased phosphorylation of Y-188; when associated with A-203 and V-209.
In AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation.
In THPH12 and AHUS6; cells transfected with the mutant are less effective in converting C3b to iC3b on the cell surface after complement activation.
Serine/arginine repetitive matrix protein 2
Abolishes the targeting to mitochondrial outer membrane.
Diminishes interaction with PRKN in presence of PINK1. Abolishes phosphorylation by PINK1 and interaction with PRKN in presence of PINK1; when associated with Ala-111.
Diminishes interaction with PRKN in presence of PINK1. Abolishes phosphorylation by PINK1 and interaction with PRKN in presence of PINK1; when associated with Ala-442.
Does not affect its ability to cluster mitochondria; when overexpressed.
Does not affect the targeting to mitochondrial outer membrane.
Found in a patient with hereditary motor and sensory neuropathy; unknown pathological significance.
Found in a patient with hereditary motor neuropathy; unknown pathological significance.
Found in a patient with intermediate Charcot-Marie-Tooth disease; unknown pathological significance.
In CMT2A2A and CMT2A2B; decreased function in mitochondrial fusion; reduced homo-oligomerization; no effect on hetero-oligomerization with MFN1.
In CMT2A2A; also found in patients with an unclassified form of Charcot-Marie-Tooth disease; unknown pathological significance.
In CMT2A2A; requires 2 nucleotide substitutions.
In CMT2A2A; unknown pathological significance.
In CMT2A2B; unknown pathological significance.
In HMSN6A; severely reduced homo-oligomerization; no effect on hetero-oligomerization with MFN1.
Interacts with PRKN in absence of PINK1; when associated with Glu-111.
Interacts with PRKN in absence of PINK1; when associated with Glu-442.
Loss of function in promoting mitochondrial fusion.
Loss of phosphorylation; when associated with 41-P-Y-42 and 66-S-Y-67. Greatly decreases NEDD4-binding; when associated with 41-P-Y-42 and 66-S-Y-67. No effect on PTEN-binding; when associated with 41-P-Y-42 and 66-S-Y-67.
Loss of phosphorylation; when associated with 41-P-Y-42 and 75-S-Y-76. Greatly decreases NEDD4-binding; when associated with 41-P-Y-42 and 75-S-Y-76. No effect on PTEN-binding; when associated with 41-P-Y-42 and 75-S-Y-76.
Loss of phosphorylation; when associated with 66-S-Y-67 and 75-S-Y-76. Greatly decreases NEDD4-binding; when associated with 66-S-Y-67 and 75-S-Y-76. No effect on PTEN-binding; when associated with 66-S-Y-67 and 75-S-Y-76.
Diphosphorylated at Ser-21 and Ser-23, also called form S2.
Monophosphorylated at Ser-23, also called form S1.
In NEDHYMS; decreased protein stability; strong decreased editing activity.
In NEDHYMS; unknown pathological significance; altered ratio of alternative splicing.
In NEDHYMS; unknown pathological significance; mild decreased editing activity.
In COXPD23; unknown pathological significance.
tRNA modification GTPase GTPBP3, mitochondrial
In ZTTKS; unknown pathological significance; de novo mutation associated in cis with S-1637.
In ZTTKS; unknown pathological significance; de novo mutation associated in cis with Y-1843.
Abolishes kinase activity but does not affect expression levels or binding to RACK1.
In HOMG1; impairs heterodimer formation resulting in intracellular retention.
In HOMG1; loss of function; no effect on cell membrane localization.
No effect on function or cell membrane localization.
Significantly decreases autophosphorylation. Does not alter binding to RACK1 but prevents inhibition by RACK1.
Significantly decreases autophosphorylation. Does not alter binding to RACK1 or inhibition by RACK1.
Transient receptor potential cation channel subfamily M member 6
Spermidine/spermine N(1)-acetyltransferase-like protein 1
Chromodomain-helicase-DNA-binding protein 7
Found in a patient with cleft lip and palate; unknown pathological significance.
In CHARGES and HH5; has no effect on interaction with CHD8.
In CHARGES and HH5; unknown pathological significance.
In CHARGES; no effect on interaction with CHD8.
In CHARGES; unknown pathological significance.
In CHARGES; unknown pathological significance; has no effect on interaction with CHD8.
In HH5; phenotype consistent with Kallmann syndrome.
In HH5; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism.
In RILDBC1; has no defect in protein synthesis.
Constitutively interacts with YWHAZ; when associated with E-172.
Constitutively interacts with YWHAZ; when associated with E-461.
Found in a truncated form isolated from Caco-2 cells treated with butyrate.
Loss of function and loss of interaction with RAC1.
Loss of function and loss of interaction with RAC1. Loss of localization to membranes.
Loss of interaction with NOXO1 and NCF1. Loss of localization to membranes. Partial loss of function.
Loss of phosphorylation. Loss of interaction with YHAWZ; when associated with A-172.
Loss of phosphorylation. Loss of interaction with YHAWZ; when associated with A-461.
In isoform 3, isoform 5, isoform 6 and isoform 7.
Does not affect protein folding and binding to UGGT1 or UGGT2.
Abolishes phosphorylation by PKA; disrupts heterotrimer stability.
Fails to localize to plasma membranes and failed to activate Rho-dependent serum response factor-mediated transcription and actin stress fiber formation.
Guanine nucleotide-binding protein subunit alpha-13
Approximately 3-fold increased autophosphorylation.
Approximately 30-fold increased autophosphorylation (constitutively active mutant).
In HYC3; unknown pathological significance.
Loss of interaction with MAP1LC3C; when associated with A-544.
Loss of interaction with MAP1LC3C; when associated with A-547.
Loss of interaction with MAP1LC3C; when associated with A-577 and A-578.
Loss of interaction with MAP1LC3C; when associated with A-577 and A-581.
Loss of interaction with MAP1LC3C; when associated with A-578 and A-581.
Mucosal addressin cell adhesion molecule 1
Chromosome alignment-maintaining phosphoprotein 1
Down-regulates both proliferation of psoriatic T-cells and IFN-gamma production; suppresses keratinocyte growth when part of the altered peptide epitope S1.
Down-regulates both proliferation of psoriatic T-cells and IFN-gamma production; suppresses keratinocyte growth when part of the altered peptide epitope S4.
Down-regulates proliferation of psoriatic T-cells and IFN-gamma production when part of the altered peptide epitope S1.
Down-regulates proliferation of psoriatic T-cells and IFN-gamma production when part of the altered peptide epitope S2.
No significant effect on T-cell proliferation but can induce IFN-gamma production when part of the altered peptide epitope S2.
No significant effect on T-cell proliferation but reduces IFN-gamma production when part of the altered peptide epitope S2.
No significant effect on T-cell proliferation but reduces IFN-gamma production when part of the altered peptide epitope S4.
No significant effect on T-cell proliferation or IFN-gamma production when part of the altered peptide epitope S1.
Impaired MEK phosphorylation and autophosphorylation activities. No effect on KSR2 binding.
Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. Loss of IL1-stimulated MEK phosphorylation activity but not of IL1-stimulated autophosphorylation activity. No effect on KSR2 binding.
Loss of MEK phosphorylation activity and almost abolished autophosphorylation activity. No effect on KSR2 binding.
Mitogen-activated protein kinase kinase kinase 8
In GKAF; unknown pathological significance; homozygous patient fibroblasts have impaired ability to progress through the cell cycle; decreased protein abundance in patient fibroblasts.
Abolishes activation of serine/threonine-protein kinase activity and has only weak activity.
Abolishes autophosphorylation on tyrosine but still active on exogenous substrates.
Abolishes dependence to reducing agents; when associated with V-29; A-89; A-154; A-168; A-169; A-204; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-154; A-168; A-169; A-204; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-204 and A-286.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-204; and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-169; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-168; A-204; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-154; A-169; A-204; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-29; V-70; A-89; A-168; A-169; A-204; A-286 and A-339.
Abolishes dependence to reducing agents; when associated with V-70; A-89; A-154; A-168; A-169; A-204; A-286 and A-339.
Maternal embryonic leucine zipper kinase
Phosphomimetic mutant that has similar kinase activity as wild-type.
Strongly inhibits interaction with PPP1R8. Enhances enzymatic activity.
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6
In MYPBB; loss of interaction with CACNA1S.
SH3 and cysteine-rich domain-containing protein 3
In CILD22; loss of interaction with DNAAF11.
In CILD22; loss of interaction with DNAL1.
In CILD22; no loss of interaction with DNAAF11.
In non-small cell lung cancer cell lines.
Zinc finger MYND domain-containing protein 10
Conserved oligomeric Golgi complex subunit 5
Partial loss of phosphorylation; when associated with F-192 or with F-222.
Partial loss of phosphorylation; when associated with F-197. Complete loss of phosphorylation; when associated with F-222.
Partial loss of phosphorylation; when tested individually or when associated with F-197. Complete loss of phosphorylation; when associated with F-192.
Transmembrane and immunoglobulin domain-containing protein 2
Oxysterol-binding protein-related protein 6
25% decrease in enzyme activity; when associated with S-193. Abolishes enzyme activity; when associated with S-55; S-58 and S-193.
50% decrease in enzyme activity; when associated with S-55. 90% decrease in enzyme activity; when associated with S-193. Abolishes enzyme activity; when associated with S-55; S-190 and S-193.
50% decrease in enzyme activity; when associated with S-58. Abolishes enzyme activity; when associated with S-58; S-190 and S-193.
90% decrease in enzyme activity; when associated with S-58. 25% decrease in enzyme activity; when associated with S-190. Abolishes enzyme activity; when associated with S-55; S-58 and S-190.
Accelerates dephosphorylation of ERN1; when associated with A-193.
Accelerates dephosphorylation of ERN1; when associated with A-58.
Decreased hydroxymethylbilane synthase activity.
Found in a patient with unclear porphyria-related biochemical findings and abdominal pain; unknown pathological significance; does not affect hydroxymethylbilane synthase activity; does not affect Vmax; does not affect KM; does not affect thermal stability.
In AIP; 19% of wild-type deaminase activity.
In AIP; 46% wild-type deaminase activity; decreased enzyme stability.
In AIP; complete loss of deaminase activity.
In AIP; decreased deaminase activity due to defective enzyme-intermediate complexes turnover and regeneration of free enzyme molecules.
In AIP; decreased hydroxymethylbilane synthase activity; results in less than 5% of wild-type activity; 2-fold decrease of Vmax; 33-fold increase of KM.
In AIP; less than 1% of wild-type activity.
In AIP; less than 1% of wild-type deaminase activity.
In AIP; loss of hydroxymethylbilane synthase activity; 1% of wild-type activity; lower thermal stability than wild-type enzyme.
In AIP; loss of hydroxymethylbilane synthase activity; affects protein conformation; lower thermal stability than wild-type enzyme.
In AIP; loss of hydroxymethylbilane synthase activity; results in less than 1% of wild-type deaminase activity.
In AIP; severe decrease in deaminase activity.
In AIP; severe decrease of deaminase activity.
In AIP; unknown pathological significance.
In AIP; unknown pathological significance; decreased hydroxymethylbilane synthase activity; has 80% of wild-type deaminase activity.
In AIP; unknown pathological significance; decreased hydroxymethylbilane synthase activity; results in 30% of wild-type activity; 3-fold decrease of Vmax; normal KM; affects protein conformation.
In AIP; unknown pathological significance; has 80% of wild-type deaminase activity.
Loss of hydroxymethylbilane synthase activity.
Loss of ZDHH20-catalyzed palmitoylation. Shows only a slight reduction in the Vmax and a small increase in the Km towards palmitoyl-CoA in comparison with wild-type.
No effect on ZDHH20-catalyzed palmitoylation.
Activated at more negative voltages. No effect on inhibition by HMIMP.
Activated at more negative voltages. Slower rate of inactivation. Impaired inhibition by HMIMP. No effect on channel inhibition by Iberiotoxin.
Calcium-activated potassium channel subunit alpha-1
Decreased localization to the plasma membrane. Abolishes localization to the plasma membrane; when associated with A-118 and A-121.
Decreased localization to the plasma membrane. Abolishes localization to the plasma membrane; when associated with A-119 and A-121.
Found in a patient with epilepsy; unknown pathological significance; no effect on voltage-dependent sensitivity.
Found in a patient with epileptic encephalopathy; unknown pathological significance; no effect on voltage-dependent sensitivity.
Found in patient with epilepsy; unknown pathological significance.
In LIWAS; loss of voltage-gated potassium channel activity.
In PNKD3 and EIG16; increased sensitivity to voltage-dependent activation resulting in increased channel activity; no change in calcium sensitivity.
In PNKD3; may have a synergistic effect with ethanol in the triggering of symptoms.
Induces reduction in the coupling between calcium and channel opening.
Loss of heme-induced channel inhibition.
No effect in the coupling between calcium and channel opening.
No effect on activation voltage. No effect on inhibition by HMIMP.
Interleukin-1 receptor accessory protein-like 1
Abolished cholesterol O-acyltransferase activity.
Abolished ubiquitination and sterol-regulated stabilization.
Cysteine sulfenic acid (-SOH); alternate
Does not affect ubiquitination and sterol-regulated stabilization.
Does not affect ubiquitination and sterol-regulated stabilization; when associated with R-279.
Does not affect ubiquitination and sterol-regulated stabilization; when associated with R-54.
Glycyl cysteine thioester (Cys-Gly) (interchain with G-Cter in ubiquitin); alternate
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-100, R-102, R-108, R-242 and R-299.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-80, R-100, R-102, R-108 and R-242.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-80, R-100, R-102, R-108 and R-299.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-80, R-100, R-102, R-242 and R-299.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-80, R-100, R-108, R-242 and R-299.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-49, R-80, R-102, R-108, R-242 and R-299.
In K-null mutant; does not affect ubiquitination and sterol-regulated stabilization; when associated with R-80, R-100, R-102, R-108, R-242 and R-299.
Leucine-rich repeat and fibronectin type-III domain-containing protein 2
Queuine tRNA-ribosyltransferase catalytic subunit 1
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1
Radiation-inducible immediate-early gene IEX-1
Abolished phosphorylation by ATM and impaired ability to promote DNA repair.
In DKCB3; disrupts telomerase localization to Cajal bodies resulting in misdirection of telomerase RNA to nucleoli.
In DKCB3; shortened telomeres; disrupts telomerase localization to Cajal bodies resulting in misdirection of telomerase RNA to nucleoli.
In LAD3; unknown pathological significance; decreases cell adhesion in hematopoietic cells; requires 2 nucleotide substitutions.
Transcription initiation factor TFIID subunit 11
Impairs binding to S-adenosyl-L-methionine. Significantly reduces N-methyltransferase activity.
Significantly reduces N-methyltransferase activity.
Peptidyl-tRNA hydrolase 2, mitochondrial
Tumor necrosis factor receptor superfamily member 12A
Zinc finger and BTB domain-containing protein 9
Abolishes nuclear localization; when associated with A-482 and A-485.
Abolishes nuclear localization; when associated with A-482 and A-493.
Abolishes nuclear localization; when associated with A-485 and A-493.
Abolishes nuclear location. Decreases enzyme activity. Retains nuclear location and abolishes enzyme activity; when associated with R-378.
Catalytically inactive. Loss of serine binding. No effect on nuclear location.
Decreased enzyme activity. Abolishes DNA binding.
In NEDMAS; impaired serine-activation of enzyme resulting in a significant decrease in the first step of the aminoacylation reaction; reduced protein stability; reduced protein expression.
Mildly decreased enzyme activity. Nearly abolishes DNA binding.
Retains nuclear location and abolishes enzyme activity; when associated with V-383.
Renal cancer differentiation gene 1 protein
Abolishes thioester intermediate formation.
NEDD8-activating enzyme E1 catalytic subunit
No effect on NEDD8 adenylation or thioester intermediate formation; impairs NEDD8 transfer to UBE2M.
No effect on NEDD8 adenylation; impairs thioester intermediate formation.
Reduces affinity for UBE2M; when associated with A-192 and A-195.
Reduces affinity for UBE2M; when associated with A-192 and A-197.
Reduces affinity for UBE2M; when associated with A-195 and A-197.
Reduces affinity for UBE2M; when associated with A-214.
Reduces affinity for UBE2M; when associated with A-217.
Catalytically inactive but does not affect integrin binding. Impairs leukotriene B4 synthesis in activated neutrophils.
Complete loss of bactericidal activity; when associated with E-27 and E-30.
Complete loss of bactericidal activity; when associated with E-27 and E-35.
Impairs bactericidal activity; when associated with D-138.
Impairs bactericidal activity; when associated with E-122.
Impairs bactericidal activity; when associated with E-127.
Impairs bactericidal activity; when associated with E-128.
Impairs bactericidal activity; when associated with E-135.
Impairs bactericidal activity; when associated with E-57.
Impairs bactericidal activity; when associated with E-72 and E-73.
Impairs bactericidal activity; when associated with E-72 and E-77.
Impairs bactericidal activity; when associated with E-73 and E-77.
Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-120.
Moderately reduced integrin binding. Greatly reduced integrin binding but no effect on catalytic activity; when associated with E-94.
No effect on integrin binding; when associated with K-68.
No effect on integrin binding; when associated with S-49.
Reduces bactericidal activity to 18% against B.subtilis and to 12% against S.aureus. Complete loss of bactericidal activity; when associated with E-87 and E-99.
Reduces bactericidal activity to 20% against B.subtilis and to 10% against S.aureus. Complete loss of bactericidal activity; when associated with E-99 and E-104.
Reduces bactericidal activity to 20% against B.subtilis and to 4% against S.aureus. Complete loss of bactericidal activity; when associated with E-30 and E-35.
Reduces bactericidal activity to 25% against B.subtilis and to 10% against S.aureus. Complete loss of bactericidal activity; when associated with E-87 and E-104.
Endonuclease domain-containing 1 protein
In OPTB7; a patient with osteoclast-poor osteopetrosis.
In OPTB7; one patient with osteoclast-poor osteopetrosis.
In OPTB7; two patients with osteoclast-poor osteopetrosis.
In OPTB7; two siblings with osteoclast-poor osteopetrosis.
Tumor necrosis factor receptor superfamily member 11A
Abolishes signaling through accumulation of intracellular calcium and phosphoinositide; no effect in signaling through MAPK.
Decreases cell surface expression; when associate with A-222.
Decreases cell surface expression; when associated with A-30. Loss of sensitivity towards all tested proteases.
Increase of sensitivity towards tryptase.
Loss of palmitoylation; increases surface expression and internalization following trypsin activation, decreases sensitivity and intracellular calcium signaling, increases ERK activation through G(i) subunit alpha.
No defect in ligand-mediated receptor activation.
Proteinase-activated receptor 2, alternate cleaved 1
Proteinase-activated receptor 2, alternate cleaved 2
Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-363.
Reduces receptor desensitization and internalization, activates ERK1/2; when associated with A-366.
Severe reduction in ligand-mediated receptor activation.
Slight reduction in ligand-mediated receptor activation.
In MCOPCB10; dramatic reduction in retinol binding; has greater affinity for the STRA6 receptor.
Mitochondrial import receptor subunit TOM70
Unable to induce IRF3 activation upon Sendai virus infection. Loss of interaction with HSPA8 and HSP90AA1. No effect on mitochondrial location.
Decreased palmitoylation. Abolishes palmitoylation; when associated with S-264.
Decreased palmitoylation. Abolishes palmitoylation; when associated with S-265.
In HDBSCC; normal location at the cell membrane.
In HDBSCC; the mutant is retained in the endoplasmic reticulum.
No effect on inflammasome activation upon dsRNA-binding.
Does not change transcriptional repression activity.
In WT6; inhibits transcriptional repression activity.
Inhibits transcriptional repression activity.
Loss of interaction with BTRC. Reduced ubiquitination. Decreased proteasomal degradation in G2. Decreased average time from nuclear envelope breakdown to anaphase onset. Increased number of lagging chromosomes and chromosome bridges in anaphase and prematurely separated sister chromatids. Reduced MAD2 levels.
Abolished ability to bind DNA and abolished ability to promote class switch recombination (CSR) in B-cells.
Abolished interaction with PCNA. Cells are hypersensitive to ionizing radiations.
Cells are hypersensitive to ionizing radiations. Abolished ability to form a covalent cross-link with DNA. Abolished binding to single-stranded DNA (ssDNA).
Cells are hypersensitive to ionizing radiations. Abolished ability to form a covalent cross-link with DNA. Does not affect single-stranded DNA (ssDNA)-binding. Does not affect ability to promote class switch recombination (CSR) in B-cells.
Strongly reduced binding to single-stranded DNA.
Thiazolidine linkage to a ring-opened DNA abasic site
Abolished association with BTRC without affecting protein stability.
In CNM6; unknown pathological significance.
In SFMMP; mild destabilization of the protein.
In an ovarian endometrioid sample; somatic mutation.
Loss of kinase activity. Does not affect ability to activate EIF2AK4/GCN2 in response to mild ribosome collision.
Mimics phosphorylation; impaired ribosome-binding.
Mitogen-activated protein kinase kinase kinase 20
Slight loss of autophosphorylation activity.
Cyclic AMP-dependent transcription factor ATF-3
De novo variant found in a patient with childhood apraxia of speech; unknown pathological significance.
In breast cancer; loss of CDK6 interaction.
Complete loss of interaction with TAPBP, resulting in impaired PLC assembly and antigen presentation.
Impairs allosteric coupling of peptide transport to ATP hydrolysis, converting the unidirectional active pump into a passive bidirectional nucleotide-gated facilitator. Inactive in peptide transport when associated with 'A-638' of TAP2.
In a lung cancer cell line deficient in MHC class I presentation.
In allele TAP1*02:01, allele TAP1*03:01, allele TAP1*04:01 and allele TAP1*x.
In allele TAP1*02:01, allele TAP1*04:01 and allele TAP1*x.
EF-hand calcium-binding domain-containing protein 9
Vacuolar protein-sorting-associated protein 25
Electrogenic aspartate/glutamate antiporter SLC25A12, mitochondrial
In DEE39; decreased antiporter activity; significant loss in ability to transport aspartate or glutamate; no effect on localization to mitochondrial inner membrane; no effect on protein abundance.
In DEE39; loss of antiporter activity; unable to transport aspartate or glutamate; no effect on localization to mitochondrial inner membrane; no effect on protein abundance.
Glycylpeptide N-tetradecanoyltransferase 2
In DEE5; could form a heterodimer with SPTBN1 but the heterodimer is thermally unstable; suggests a dominant negative effect.
Spectrin alpha chain, non-erythrocytic 1
In a bladder carcinoma NOS sample; somatic mutation.
No effect on focal adhesion subcellular localization. Does not affect colocalization with F-actin.
No effect on localization with actin. Decreases localization in focal adhesion. Fails to regulate focal adhesion dynamics. Decreases cell migration.
Abolishes enzyme activity. Unable to mediate serine depalmitoleoylation of WNT proteins.
Palmitoleoyl-protein carboxylesterase NOTUM
Abolishes localization to the nuclear envelopee; abolishes its localization to the nuclear envelope; impairs localization of SUN1 and EMD to the nuclear envelope.
Impairs organization of the nuclear envelope; abolishes its localization to the nuclear envelope; impairs localization of SUN1 and EMD to the nuclear envelope.
Found in individuals with delayed sleep phase syndrome; has higher frequency in affected individuals than in healthy controls; unknown pathological significance.
Cation channel sperm-associated auxiliary subunit TMEM249
Killer cell lectin-like receptor subfamily F member 1
Abolishes PKB/AKT1-mediated phosphorylation. Repressed transactivation.
Abolishes interaction with ASXL1 and NCOA1.
Abrogates interaction with NCOR1 or NCOR2. Increased affinity for NCOR1 and NCOR2 in the presence of BMS493. Increased transcriptional activity in the presence of agonist and decreased activity in the presence of neutral antagonist.
Abrogates sumoylation in the presence or absence of ATRA and primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-166; R-171 and R-399.
Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-166 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-399.
Cytoplasmic in the absence of ATRA and reduced transcriptional activity in the presence of ATRA. Low sumoylation levels in the presence of ATRA; when associated with R-399. Nuclear localization and enhanced transcriptional activity; when associated with R-171 and R-399. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-171 and R-399.
Impairs interaction with ASXL1 and NCOA1; when associated with Q-412.
Impairs interaction with ASXL1 and NCOA1; when associated with Q-415.
In the absence of ATRA, abolishes sumoylation and is mainly nuclear. In the presence of ATRA, some sumoylation, cytoplasmic location, reduced transcriptional activity and no SENP6 binding. Low sumoylation levels in the presence of ATRA and nuclear location in the absence of ATRA; when associated with R-166 or with R-171. Primarily nuclear localization and enhanced ATRA-mediated transcriptional activity; when associated with R-147; R-166 and R-171.
No effect on PKB/AKT1-mediated phosphorylation. No repression of transactivation.
No effect on PKB/AKT1-mediated phosphorylation. Repressed transactivation.
No effect on heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, no increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-369.
No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-219.
No effect on heterodimerization with RARA. On ATRA treatment, localizes to the nucleus, and increased protein levels; when associated with A-369.
Some inhibition of heterodimerization with RARA. On ATRA treatment, localizes to both nucleus and cytoplasm, increase in protein levels, and decrease in RARA-mediated transcriptional activity; when associated with E-219.
Sterile alpha motif domain-containing protein 3
In DYT32; unknown pathological significance.
Vacuolar protein sorting-associated protein 11 homolog
In allele HA-1H; induction of CTL recognition for epitope HA-1.
In CBG deficiency; Leuven; decreased cortisol-binding affinity.
In CBG deficiency; Lyon; decreased cortisol-binding affinity.
Ciliary-associated calcium-binding coiled-coil protein 1
50% decrease in NAD and NADP-dependent dehydrogenase specific activity. Reduced affinity for magnesium.
80% decrease in NAD-dependent dehydrogenase specific activity. 18% decrease in NADP-dependent dehydrogenase specific activity. Reduced affinity for magnesium.
82% decrease in NAD-dependent dehydrogenase specific activity. 65% decrease in NADP-dependent dehydrogenase specific activity. Reduced affinity for magnesium.
84% decrease in NAD-dependent dehydrogenase specific activity. 36% increase in NADP-dependent dehydrogenase specific activity. Reduced affinity for magnesium.
Almost complete loss of NAD-dependent dehydrogenase specific activity. 50% decrease in NADP-dependent dehydrogenase specific activity.
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Complete loss of NAD and NADP-dependent dehydrogenase specific activity.
Significant loss of NAD and NADP-dependent dehydrogenase specific activity.
Abolishes binding to H3K4me3; when associated with A-43. Abolishes binding to H3K4me3; when associated with A-65.
Abolishes binding to H3K4me3; when associated with A-50.
Abolishes histone methyltransferase activity.
Impairs phosphorylation by CDK1 and dissociation from chromatin when cells enter mitosis; when associated with A-120.
Impairs phosphorylation by CDK1 and dissociation from chromatin when cells enter mitosis; when associated with A-69.
In MRXSSD; abolishes histone methyltransferase activity; reduces transcriptional activation activity.
Reduces transcriptional activation activity.
Phosphomimetic mutant; enhances kinase activity.
Calcium-binding and coiled-coil domain-containing protein 1
In IMD82; constitutively active protein tyrosine kinase activity.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
WD repeat and FYVE domain-containing protein 2
Zinc finger CCHC domain-containing protein 18
In CDG2F; results in decreased CMP-sialic acid transmembrane transporter activity when expressed in a heterologous system; does not affect localization to Golgi apparatus.
In a colorectal cancer sample; somatic mutation; no effect Wnt signlaing upon RSPO1-binding.
Leucine-rich repeat-containing G-protein coupled receptor 6
Chloride intracellular channel protein 2
In MRXS32; results in stimulation of RYR channels activity with channels remaining open for longer times; the mutation may impair insertion of the protein into the membrane to form a functioning ion channel.
In COXPD13; the mutation alters multimerization of the protein.
In DFNB70; results in a hypofunctional protein leading to disturbed enzyme trimerization and impaired mitochondrial RNA import.
Inhibits poly(A) polymerase and RNA degradation activities. Does not inhibit the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity.
Inhibits poly(A) polymerase and RNA degradation activities. Inhibits the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity.
Polyribonucleotide nucleotidyltransferase 1, mitochondrial
Stimulates in vitro poly(A) polymerase activity. Inhibits RNA degradation activity. Does not inhibit the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity.
Stimulates in vitro poly(A) polymerase activity. Inhibits RNA degradation activity. Inhibits the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity.
Myb/SANT-like DNA-binding domain-containing protein 2
In isoform 3, isoform 4, isoform 6 and isoform 11.
In isoform 5, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 11.
Long-chain fatty acid transport protein 2
Strongly reduced the ubiquitination directing activity of the protein.
Abolishes both sumoylation and repression; when associated with R-779. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-554 and R-779.
Abolishes both sumoylation and repression; when associated with R-804. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-554 and R-804.
Abolishes interaction with CBX5; when associated with E-488.
Abolishes interaction with CBX5; when associated with E-490.
Complete loss of the PHD finger-mediated stimulatory effect on sumoylation. Loss of binding UBE2I.
Disrupts the interaction with ZNF350 and amost completely relieves the transcription repressive effect of sumoylated TRIM28.
Enhances Dox-induced CDKN1A/p21 promoter activation. Decreased sumoylation with or without Dox-treatment.
Greatly reduced interaction with PPP1CA.
Greatly reduced sumoylation. Little further effect on sumoylation; when associated with A-653 and/or A-668.
Greatly reduced sumoylation. Little further effect on sumoylation; when associated with A-668 and/or A-709.
Increased interaction with PPP1CA. Greatly decreased phosphorylation on S-824.
Little effect on sumoylation. Little further effect on sumoylation; when associated with A-653 and/or A-709.
Moderately reduces sumoylation and repression. Abolishes both sumoylation and repression; when associated with R-575. Relieves the repressor activity on Dox-induced GADD45A transcription and 2-fold increase in phosphorylation at Ser-824; when associated with R-779 and R-804.
Modestly reduced sumoylation and repression. Abolishes both sumoylation and repression; when associated with R-554.
Modestly reduces sumoylation and repression.
No effect on interaction with PPP1CA nor on sumoylation levels. Decreased sumoylation levels; when associated with D-440 and D-824.
No effect on interaction with PPP1CA nor on sumoylation levels. Decreased sumoylation levels; when associated with D-501 and D-824.
Phosphoserine; by ATM and ATR and dsDNA kinase
Reduces nuclear localization activity of ZNF268; when associated with A-65.
Reduces nuclear localization activity of ZNF268; when associated with A-68.
Some reduced sumoylation and repression.
Some reduction in interaction with PPP1CA.
Suppresses Dox-induced CDKN1A/p21 promoter activation. No effect on sumoylation levels. Decreased sumoylation levels; when associated with D-440 and D-501.
Transcription intermediary factor 1-beta
In NPHS2; requires 2 nucleotide substitutions.
In NPHS2; unknown pathological significance.
Lipocln_cytosolic_FA-bd_dom domain-containing protein
Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial
Zinc finger CCCH domain-containing protein 10
Inactive as a heme oxygenase but active as a peroxidase.
CREB-regulated transcription coactivator 1
In GDMN; unknown pathological significance.
In GDMN; unknown pathological significance; Reduces cleavage efficiency in in vitro time course.
Ubiquitin-associated and SH3 domain-containing protein A
Disintegrin and metalloproteinase domain-containing protein 8
RecQ-mediated genome instability protein 1
Abolishes homodimerization and RNA binding; when associated with A-306.
Abolishes homodimerization and RNA binding; when associated with A-310.
Abolishes interaction with DDX6; when associated with A-204.
Abolishes interaction with DDX6; when associated with A-206.
In MRT50; does not enhance DCP2 decapping activity.
Loss of function. Loss of targeting to the clathrin-coated pits and vesicles. Loss of interaction with DNM2, RRAGB and RRAGC. No effect on localization to the plasma membrane.
Inactive serine/threonine-protein kinase PLK5
Abolishes binding to ECD, EFTUD2, RPB1, TELO2 and UBR5.
Abolishes binding to KPNA2 and impairs binding to KPNB1, IPO7 and TMPO1; when associated with E-192.
Abolishes binding to KPNA2 and impairs binding to KPNB1, IPO7 and TMPO1; when associated with E-196.
Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-166.
Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-175.
Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-225.
Abolishes binding to KPNA2, KPNB1 and IPO7 and impairs binding to TMPO1; when associated with E-229.
Increases protein stability and half-life, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-100.
Increases protein stability and half-life, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-104.
Increases protein stability, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-92.
Increases protein stability, nuclear accumulation and repressor activity on E-cadherin/CDH1 promoter; when associated with A-96.
Increases protein stability. Does not affect repressor activity on E-cadherin/CDH1 promoter.
Impairs hormone binding and ligand-dependent conformational changes.
In GRTHD; impairs hormone binding and ligand-dependent conformational changes.
Inhibits homodimer formation on a minimal response element (in vitro).
Modestly inhibits homodimer formation on a minimal response element (in vitro).
Abolishes interaction with CHMP1B; diminishes interaction with IST1.
Abolishes interaction with CHMP6, no effect on interaction with CHMP1A.
Defective in ATP-binding. Causes membrane association. Induces vacuolation of endosomal compartments and impairs cholesterol sorting. Inhibits HIV-1 release. Greatly diminishes localization to punctate class E compartments and partially restores HIV-1 release; when associated with D-64. Greatly diminishes localization to punctate class E compartments; when associated with D-173.
Defective in ATP-hydrolysis. Causes membrane association. Induces vacuolation of endosomal compartments and impairs cholesterol and protein sorting. Inhibits HIV-1 release. Increases binding to CHMP1.
Found in a patient with a CIMDAG-like intellectual disability syndrome; unknown pathological significance.
Found in a patient with non-specific intellectual disability; unknown pathological significance.
Greatly diminishes localization to punctate class E compartments and partially restores HIV-1 release; when associated with Q-173.
Greatly diminishes localization to punctate class E compartments; when associated with Q-173.
In CIMDAG; has a dominant negative effect on the regulation of endosomal size resulting in enlarged endosomal vacuoles; patient cells also have abnormal nuclear envelope morphology and primary cilium defects; no effect on protein abundance in patient cells.
In CIMDAG; has a dominant negative effect on the regulation of endosomal size resulting in enlarged endosomal vacuoles; patient cells also have abnormal nuclear envelope morphology and primary cilium defects; no effect on protein abundance in patient cells; patient-derived induced erythroblasts show defective cytokinesis.
In CIMDAG; patient peripheral red blood cells show abnormal CD71 expression indicating defective endosomal trafficking.
In CIMDAG; unknown pathological significance.
Modestly reduces interaction with CHMP6.
Vacuolar protein sorting-associated protein 4A
Glycosyltransferase 8 domain-containing protein 2
Translation machinery-associated protein 7
N-linked (GlcNAc...) (keratan sulfate) asparagine
Complete loss of sumoylation; when associated with R-252 and R-253.
Complete loss of sumoylation; when associated with R-252 and R-256.
Complete loss of sumoylation; when associated with R-253 and R-256.
Endoplasmic reticulum-Golgi intermediate compartment protein 2
Insulin-like growth factor-binding protein-like 1
In SPG5A; unknown pathological significance.
In NEDLBA; almost complete loss of phosphatase activity in an in vitro assay; decreased interaction with PP2A subunit A PPP2R1A/PPP2R1B; strongly decreased interaction with PP2A subunit B components PPP2R2A and PPP2R3A; increased interaction with PP2A subunit B component STRN3; no effect on interaction with PP2A subunit B components PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D and PPP2R5E.
In NEDLBA; almost complete loss of phosphatase activity in an in vitro assay; strong decrease in C-terminal methylation; no effect on the interaction with PP2A subunit A PPP2R1A/PPP2R1B; decreased interaction with PP2A subunit B components PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E and PPP2R3A; no effect on interaction with PP2A subunit B component PPP2R2A.
In NEDLBA; decreased phosphatase activity in an in vitro assay; no effect on C-terminal methylation; no effect on the interaction with PP2A subunit A PPP2R1A/PPP2R1B; no effect on interaction with PP2A subunit B components.
In NEDLBA; decreased phosphatase activity in an in vitro assay; no effect on the interaction with PP2A subunit A PPP2R1A/PPP2R1B; decreased interaction with PP2A subunit B component PPP2R5D; increased interaction with PP2A subunit B component STRN3; no effect on interaction with other PP2A subunit B components.
In NEDLBA; decreased phosphatase activity in an in vitro assay; no effect on the interaction with PP2A subunit A PPP2R1A/PPP2R1B; increased interaction with PP2A subunit B component STRN3; no effect on interaction with other PP2A subunit B components.
In NEDLBA; increased phosphatase activity in an in vitro assay; no effect on C-terminal methylation; decreased interaction with PP2A subunit A PPP2R1A/PPP2R1B; loss of interaction with PP2A subunit B components PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D and PPP2R5E; no effect on interaction with PP2A subunit B components PPP2R2A and PPP2R3A.
In NEDLBA; loss of phosphatase activity in an in vitro assay; complete loss of interaction with PP2A subunit A PPP2R1A/PPP2R1B; interacts with alpha4/IGBP1; loss of interaction with PP2A subunit B components.
In NEDLBA; loss of phosphatase activity in an in vitro assay; strong decrease in C-terminal methylation; decreased interaction with PP2A subunit A PPP2R1A/PPP2R1B; loss of interaction with PP2A subunit B component PPP2R2A; decreased interaction with PP2A subunit B components PPP2R5A, PPP2R5B, PPP2R5E, PPP2R3A and STRN3.
In NEDLBA; may be expressed at very low levels, if any.
In NEDLBA; no effect on phosphatase activity in an in vitro assay; no effect on the interaction with PP2A subunit A PPP2R1A/PPP2R1B; no effect on interaction with PP2A subunit B components.
In NEDLBA; severe decrease in phosphatase activity in an in vitro assay; strong decrease in C-terminal methylation; decreased interaction with PP2A subunit A PPP2R1A/PPP2R1B; loss of interaction with PP2A subunit B components PPP2R2A, PPP2R5A, PPP2R5B, PPP2R5E, PPP2R3A and STRN3; decreased interaction with PP2A subunit B components PPP2R5C and PPP2R5D.
In NEDLBA; unknown pathological significance.
Loss of binding to PP2A B-alpha regulatory subunit.
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
Guanine nucleotide-binding protein-like 3
Abolishes interaction with PPP1CB and ability to regulate myosin PP1 activity.
Abolishes kinase activity and ability to induce senescence.
Abrogates phosphorylation by PKB/AKT1. Does not affect ability to induce senescence.
Prevents phosphorylation and activation by STK11/LKB1 complex. Abolishes ability to induce senescence.
Thiosulfate sulfurtransferase/rhodanese-like domain-containing protein 3
Loss of autophosphorylation and of endoribonuclease activity. Inhibition of growth arrest.
No effect on dimerization. No effect on interaction with P4HB; when associated with S-148 and S-332.
No effect on dimerization. Weakens dimer; when associated with S-148. No effect on interaction with P4HB; when associated with S-109 and S-148.
No effect on dimerization. Weakens dimer; when associated with S-332. Abolishes interaction with PDIA6. Prolonged splicing of XBP1, probably due to prolonged activation of PDIA6. Inhibits formation of oxidized multimeric forms of ERN1 in response to ER stress. No effect on interaction with P4HB; when associated with S-109 and S-332.
Serine/threonine-protein kinase/endoribonuclease IRE1
Found in patients with female infertility; unknown pathological significance.
NACHT, LRR and PYD domains-containing protein 2
Cytoplasmic and nuclear localization. Reduced transcriptional activity of HIF1A as for wild type.
Eliminates hydroxylase activity on a HIF1A peptide.
Leads to expression of isoform p40 only.
Leads to expression of isoform p43 only.
Abolished interaction with PEX5 and translocation to peroxisomes in response to reactive oxygen species (ROS).
Decreased phosphorylation of target proteins.
Found in B-cell non-Hodgkin lymphoma; unknown pathological significance.
Found in T-prolymphocytic leukemia; unknown pathological significance.
Found in a patient with breast cancer; unknown pathological significance.
Found in a patient with early-onset breast cancer; unknown pathological significance.
Found in a patient with familial breast cancer; unknown pathological significance.
Found in a patient with familial pancreatic cancer; also found in a lung adenocarcinoma sample; unknown pathological significance; decreased phosphorylation of target proteins.
Found in a patient with familial pancreatic cancer; unknown pathological significance.
Found in patients with familial pancreatic cancer; also found in a lung adenocarcinoma sample; unknown pathological significance.
Found in patients with familial pancreatic cancer; also found in a small cell lung cancer sample; unknown pathological significance.
Found in patients with familial pancreatic cancer; unknown pathological significance.
In AT, B-cell chronic lymphocytic leukemia and familial cancer patients; no effect on phosphorylation of target proteins.
In AT, B-cell chronic lymphocytic leukemia, breast cancer patients and familial cancer patients; no effect on phosphorylation of target proteins.
In AT; also found in B-cell chronic lymphocytic leukemia and T-prolymphocytic leukemia; may be associated with increased risk for breast cancer; decreased phosphorylation of target proteins.
In AT; also found in B-cell non-Hodgkin lymphoma; increases protein abundance.
In AT; also found in T-prolymphocytic leukemia and T-cell acute lymphoblastic leukemia; lack of phosphorylation of target proteins.
In AT; also found in T-prolymphocytic leukemia and mantle cell lymphoma; lack of phosphorylation of target proteins.
In AT; also found in T-prolymphocytic leukemia; lack of phosphorylation of target proteins.
In AT; associated with T-cell acute lymphoblastic leukemia.
In AT; associated with lymphoma; decrease phosphorylation of target proteins; increases protein abundance.
In AT; associated with preleukemic T-cell proliferation; decreased phosphorylation of target proteins.
In AT; decreased phosphorylation of target proteins.
In AT; decreased protein abundance; loss of DNA damage induced protein autophosphorylation.
In AT; lack of phosphorylation of target proteins.
In AT; loss of DNA damage induced protein autophosphorylation.
In AT; might be associated with susceptibility to cancer.
In AT; mild; decreased phosphorylation of target proteins.
In AT; requires 2 nucleotide substitutions.
In AT; unknown pathological significance.
In AT; unknown pathological significance; increases protein abundance.
In AT; unknown pathological significance; no effect on phosphorylation of target proteins.
In AT; unknown pathological significance; reduces protein abundance.
In B-cell chronic lymphocytic leukemia; unknown pathological significance; no effect on phosphorylation of target proteins.
In T-prolymphocytic leukemia and B-cell chronic lymphocytic leukemia.
In T-prolymphocytic leukemia; also found in a patient with early-onset breast cancer; unknown pathological significance.
In T-prolymphocytic leukemia; also in a lung adenocarcinoma sample; somatic mutation.
In T-prolymphocytic leukemia; somatic mutation.
In a renal papillary cancer sample; somatic mutation.
Loss of DNA damage-inducible acetylation. Retains constitutive kinase activity, but blocks DNA damage-induced kinase activation. Disrupts dimer and abolishes S-1981 autophosphorylation.
Loss of IR-induced S-1893 autophosphorylation. Reduced correction of cell cycle checkpoint defects and DNA-repair activity. No effect on S-367 nor S-1981 autophosphorylation.
Loss of IR-induced S-1981 autophosphorylation. Reduced correction of cell cycle checkpoint defects and DNA-repair activity. No effect on S-367 nor S-1893 autophosphorylation. No dimer disruption.
Loss of IR-induced S-367 autophosphorylation. Reduced correction of cell cycle checkpoint defects and DNA-repair activity. No effect on S-1893 nor S-1981 autophosphorylation.
Loss of phosphorylation of target proteins.
May contribute to breast cancer; lack of phosphorylation of target proteins.
Might contribute to B-cell chronic lymphocytic leukemia.
Mimics acetylation, preventing dephosphorylation and subsequent ATM deactivation during the late stage of DNA damage response.
No effect on phosphorylation of target proteins.
Retains DNA damage-inducible acetylation and S-1981 autophosphorylation.
Ferredoxin-fold anticodon-binding domain-containing protein 1
Reduced ability to stimulate KMT2A methyltransferase activity in association with WDR5 and ASH2L.
Significant reduction in its ability to stimulate KMT2A methyltransferase activity in association with WDR5 and ASH2L.
Arrests retrograde ERGIC/cis-Golgi-to-ER transport at an early step and causes disassembly of the Golgi and disassociation of COP1 from membranes.
Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1
Increases interaction with COPG1 and PNPLA2.
Inhibits Golgi membrane recruitment of GGA1, GGA2 and GGA3; generates misprocessing of PSAP.
Prevents 2-DG-induced Golgi disassembly.
Loss of homodimerization; when associated with S-136.
Loss of homodimerization; when associated with S-138.
No effect on its haemagglutinating activity.
RNA polymerase II elongation factor ELL3
In NEDMABA; unknown pathological significance.
In isoform 2, isoform 6, isoform 8 and isoform 10.
No effect on endoplasmic reticulum location.
Transcription elongation factor A protein-like 5
Mitochondrial import inner membrane translocase subunit TIM14
Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-56. Disrupts nuclear localization.
Disrupts nuclear localization and does not bind KPNA2, KPNA4, KPNA1; when associated with A-57. Disrupts nuclear localization.
Distributed in cytoplasm. Fails to promote cell proliferation. No binding to KPNA2, KPNA4 and KPNA1.
In MRXSC; unknown pathological significance.
Glycosyltransferase 8 domain-containing protein 1
In a patient with Bardet-Biedl syndrome compound heterozygous for mutations in BBS12.
In a patient with Meckel syndrome compound heterozygous for mutations in CC2D2A.
WD repeat-containing and planar cell polarity effector protein fritz homolog
Abolishes HUWE1 binding. Does not affect oligomerization.
HUWE1-associated protein modifying stress responses
Reduces HUWE1 binding. Blocks oligomerization. Rapid proteasomal degradation.
In CMS23; reduced rates of citrate transport.
In D2L2AD; disease phenotype may include decreased activity of mitochondrial respiratory chain complex V.
In D2L2AD; no protein detected by Western blot in patient fibroblasts; severely reduced rates of citrate transport.
In D2L2AD; reduced rates of citrate transport.
In D2L2AD; severely reduced rates of citrate transport.
In D2L2AD; unknown pathological significance; very mild decrease of citrate transport rates.
Tricarboxylate transport protein, mitochondrial
Coiled-coil domain-containing protein 18
95% reduction in activity; strong reduction of receptor binding.
Abolishes binding to Link domain of TNFAIP6.
Loss of dimerization; slight reduction of activity.
E3 ubiquitin-protein ligase Itchy homolog
Greatly reduced phosphorylation on T-cell stimulation and in the presence of FYN. Increased ITCH-mediated Ub conjugation and degradation of JUNB.
Loss of ubiquitin protein ligase activity. Results in altered endosomal sorting and reduced degradation of CXCR4. Unable to inhibit MAVS-induced activation of INFB.
No effect on phosphorylation on T-cell stimulation nor in the presence of FYN.
Found in a patient with hypothalamic hamartoma; unknown pathological significance.
Probable disease-associated variant found in a patient with non-syndromic sensorineural hearing loss.
U3 small nucleolar RNA-associated protein 14 homolog A
Activated RNA polymerase II transcriptional coactivator p15
Does not affect the subcellular location.
Membrane association; releases autoinhibition.
Actin, cytoplasmic 1, N-terminally processed
In DJO; modifies cell response to latrunculin A.
N-acetylaspartate; in Actin, cytoplasmic 1, N-terminally processed
Weak methylation by a A-256 or V-256 SETD3 mutant. High methylation by a F-256 and A-274 SETD3 mutant.
Iron-sulfur cluster assembly 2 homolog, mitochondrial
Abolishes interaction with PYM1 leading to increase EJC association with spliced mRNAs; when associated with R-68; K-73 and R-117.
Abolishes interaction with PYM1 leading to increase EJC association with spliced mRNAs; when associated with R-68; R-72 and K-73.
Abolishes interaction with PYM1 leading to increase EJC association with spliced mRNAs; when associated with R-68; R-72 and R-117.
Abolishes interaction with PYM1 leading to increase EJC association with spliced mRNAs; when associated with R-72; K-73 and R-117.
Complete loss of nonsense-mediated decay activity.
Impaired nonsense-mediated decay activity.
Slightly reduced nonsense-mediated decay activity.
Putative ATP-dependent RNA helicase TDRD12
Decreased APP processing by the gamma-secretase complex.
Decreased expression levels, and decreased stimulation of presenilin endoproteolysis.
Increased expression at the cell membrane.
Induces a N-linked glycosylation on N-8.
No effect on APP processing by the gamma-secretase complex.
Constitutively active. Interacts with PARD6 proteins and GOPC.
Cytochrome c1, heme protein, mitochondrial
Abolishes endoribonuclease activity and increases RNA-binding activity.
Abolishes endoribonuclease activity without affecting RNA-binding activity.
Strongly impairs endoribonuclease activity without affecting RNA-binding activity.
Oxidoreductase-like domain-containing protein 1
Phosphomimetic mutant able to partially restore focused bipolar spindles to PLK1-depleted cells that otherwise possess aberrant spindles with diffuse or multiple gamma-tubulin signals.
Phosphomimetic mutant; abolishes the intramolecular interaction between the DENN domain and the C-terminus of the protein.
Decreased calmodulin modulator function.
Loss of the calmodulin modulator function.
No effect on the calmodulin modulator function.
Uncharacterized protein encoded by LINC03043
In AVSD2; associated with disease susceptibility.
Protein phosphatase 1 regulatory subunit 3F
About 50% loss of CSK-mediated inhibition.
CMT1A duplicated region transcript 4 protein
Iroquois-class homeodomain protein IRX-1
Can be associated with lower folate and higher homocysteine levels.
Loss of glycosylation. Abolishes enzyme activity.
Loss of glycosylation. Reduces enzyme activity.
Loss of glycosylation. Severely reduced enzyme activity.
Inactive ubiquitin carboxyl-terminal hydrolase 54
Complete loss of glyceraldehyde oxidoreductase activity.
Reduced glyceraldehyde oxidoreductase activity.
G-protein coupled receptor family C group 5 member C
Abolishes stress granule assembly and correct localization in dcp1 bodies.
Cytoplasmic polyadenylation element-binding protein 1
In ATFB15; fails to accumulate at various foci of the nuclear envelope and is diffusely distributed in the cytoplasm; shows significantly reduced permeability of the nuclear envelope compared to wild-type.
Decreased interaction with ITCH and no effect on interaction with EPN1; when associated with A-151.
Decreased interaction with ITCH and no effect on interaction with EPN1; when associated with A-197.
Endosomal transmembrane epsin interactor 1
In SPGF55; unknown pathological significance; decreased protein expression in homozygous patient sperm.
In IMD73A; dominant-negative mutant; binds GDP, but not GTP; inhibits oxidase activation and superoxide anion production in vitro.
In IMD73B; gain-of-function variant; exhibits impaired GAP-mediated GTP hydrolysis, resulting in sustained GTP association and prolonged RAC2-driven activation of downstream effectors; when transfected into cells, shows increased basal reactive oxygen species production following stimulation by PMA compared to cells transfected with wild-type; increased interaction with PAK1, compared to wild-type.
In IMD73B; unknown pathological significance; cells transfected with this variant show higher production of reactive oxygen species compared to wild-type; potential gain-of-function variant.
In IMD73B; unknown pathological significance; increased interaction with PAK1 compared to wild-type; potential gain-of-function variant.
In IMD73C; strong decrease in protein expression.
Ras-related C3 botulinum toxin substrate 2
Induces a strong reduction in phosphorylation but is still sensitive to H(2)O(2).
Increases in kcat with GMP as substrate.
Leads to aggregation. Increases in kcat with GMP as substrate.
Nuclear envelope pore membrane protein POM 121
MEF2-activating motif and SAP domain-containing transcriptional regulator
Abolishes interaction with HSP90AB1; when associated with D-40. No effect on interaction with PGR.
Abolishes interaction with HSP90AB1; when associated with D-77. No effect on interaction with PGR.
Abolishes interaction with HSP90AB1; when associated with E-33. No effect on interaction with PGR.
Abolishes interaction with HSP90AB1; when associated with E-70. No effect on interaction with PGR.
In OOHE; unknown pathological significance.
Complement C1q tumor necrosis factor-related protein 8
Coiled-coil domain-containing protein 30
Actin, gamma-enteric smooth muscle, intermediate form
Found in a severe infantile gastrointestinal motility disorder; unknown pathological significance.
In MMIHS5; interferes with proper polymerization into thin filaments leading to impaired contractility of the smooth muscle.
In MMIHS5; interferes with proper polymerization into thin filaments.
In VSCM1; interferes with proper polymerization into thin filaments.
In VSCM1; unknown pathological significance.
Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-51); by Vibrio toxins RtxA and VgrG1
Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-271); by Vibrio toxins RtxA and VgrG1
N-acetylglutamate; in Actin, gamma-enteric smooth muscle
Slightly decreased methylation by SETD3.
In variant Michigan-1; confers enhanced esterase activity and an additional zinc binding site.
Abolishes sumoylation by SUMO1. Increased IFN-gamma-mediated transactivation.
Decreased transcriptional activation. No effect on basal sumoylation. No enhancement of sumoylation on MAPK stimulation. No PRKCD-induced apoptosis. Upon IFNB induction, phosphorylated at Y-701 but not at S-708.
Enhances STAT1 nuclear translocation and interferon (IFN)-stimulated gene (ISG) expression in response to IFN-beta stimulation. Reduces viral load in infected cultured cells.
In IMD31A; affects both phosphorylation and DNA-binding activity; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27.
In IMD31A; affects the DNA-binding activity of the protein.
In IMD31A; impairs tyrosine phosphorylation; results in impaired STAT1-mediated cellular response to IFN-gamma and interleukin-27.
In IMD31A; loss of GAF and ISGF3 activation; impairs the nuclear accumulation of GAF but not of ISGF3 in heterozygous cells stimulated by IFNs; affects phosphorylation of the protein.
In IMD31B; disrupts transactivation activity in response to IFNG.
In IMD31B; found in an infant who died of a viral-like illness associated with complete STAT1 deficiency.
In IMD31B; not deleterious in terms of most STAT1 functions; causes abnormal splicing out of exon 8 from most mRNAs thereby decreasing protein levels by approximately 70%.
In IMD31C; gain of function mutation associated with increased STAT1 phosphorylation due to impaired nuclear dephosphorylation.
In IMD31C; gain of function; increases STAT1 phosphorylation due to impaired nuclear dephosphorylation; increases transactivation activity in response to IFNG.
In IMD31C; gain of function; increases basal STAT1 phosphorylation levels which are 10-20 fold higher than controls after IFNG stimulation.
In IMD31C; gain of function; increases phosphorylation in response to IFNG and IFNA due to a loss of dephosphorylation.
In IMD31C; gain of function; increases phosphorylation in response to IFNG, IFNA and IL27 due to a loss of dephosphorylation.
In IMD31C; gain of function; increases transactivation activity in response to IFNG.
Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-657.
Loss of ADP-ribosylation and increased Tyr-701 phosphorylation; when associated with Q-705.
No change in enhancement of MAPK-induced sumoylation.
No change in enhancement of MAPK-induced sumoylation. Basal interaction with PIAS1. Interaction with PIAS1 increased on MAPK stimulation.
No effect on IFN-alpha-induced STAT1 phosphorylation and nuclear translocation.
No effect on basal sumoylation. Enhances sumoylation in the presence of MAPK stimulation. Phosphorylated at S-708 upon IFNB induction.
Not phosphorylated at S-708 upon IFNB induction.
Not phosphorylated at Y-701 upon IFNB induction.
Phosphorylated at Y-701 upon IFNB induction.
Signal transducer and activator of transcription 1-alpha/beta
Strongly reduced IFN-alpha-induced STAT1 phosphorylation and nuclear translocation. Does not affect ability to homodimerize.
Major facilitator superfamily domain-containing protein 6
Loss of arylsulfatase activity and loss of ability to modulate apoptosis.
At homozygosity may be associated with Leber congenital amaurosis in some populations.
Changes the substrate specificity from GTP to ATP.
Fails to become activated by GUCA1A and by GUCA1B. Does not affect the binding to RP3.
In CACD1; unknown pathological significance.
In CORD6; decreases basal and GUCA1A-induced guanylate cyclase activity; inhibition by RD3 is less effective; does not affect endoplasmic reticulum membrane localization.
In CORD6; loss basal and GUCA1A-induced guanylate cyclase activity; does not affect endoplasmic reticulum membrane localization.
In LCA1; does not affect basal guanylate cyclase activity; reduces GUCA1A-induced guanylate cyclase activity.
In LCA1; increases basal and GUCA1A-induced guanylate cyclase activity; inhibition by RD3 is less effective; does not affect endoplasmic reticulum membrane localization.
In LCA1; loss of basal and GUCA1A-induced guanylate cyclase activity; does not affect endoplasmic reticulum membrane localization.
In LCA1; requires 2 nucleotide substitutions.
In LCA1; severely impairs basal and GUCA1A induced guanylate cyclase.
In LCA1; severely impairs basal and GUCA1A-induced guanylate cyclase activity.
In LCA1; unknown pathological significance.
Affects the nuclear location of the C-terminal fragment generated by PSEN1.
DXXLL motif involved in the interaction with GGA1
In AD; unknown pathological significance.
In AD; unknown pathological significance; loss of interaction with APP amyloid-beta peptides, hence reduced turnover of APP amyloid-beta peptides in cells.
Loss of interaction with GGA1 and PACS1. No effect on interaction with APP. Affects subcellular location, by causing increased localization to recycling endosomes. Increased APP processing by alpha-secretase, resulting in increased levels of soluble APP-alpha and C83 APP fragments. Decreased APP processing by beta-secretase, resulting in reduced levels of C99 APP fragment.
Loss of interaction with GGA1 and PACS1. No effect on interaction with APP. Affects subcellular location, increasing localization at the cell surface, possibly due to drastically decreased endocytosis. Impaired Golgi apparatus - endosome sorting. Increased amyloidogenic APP processing by beta-secretase, resulting in increased levels of soluble APP-beta and amyloid-beta protein 40 and 42. Loss of APOA5 internalization.
No effect on endocytosis. Affects LPL sorting to endosomes.
No effect on endocytosis. Decreased Golgi apparatus - endosome sorting.
No effect on the interaction with HSPA12A.
Potential nuclear localization signal for the C-terminal fragment generated by PSEN1
Strong decrease in interaction with HSPA12A.
Strong reduction in Golgi apparatus - endosome sorting. Loss of interaction with AP-1 complex.
Ubiquitin carboxyl-terminal hydrolase 17-like protein 21
Associated with susceptibility to obesity; induces a 10.4% reduction of activity (P = 0.03) when compared to the wild-type enzyme.
In PC1 deficiency; in vitro the mutation markedly impairs the catalytic activity of the enzyme; however intracellular trafficking of this mutant enzyme appears normal; retains some autocatalytic activity even though it is completely inactive on other substrates.
In PC1 deficiency; prevents processing of pro-PCSK1 and leads to its retention in the endoplasmic reticulum.
Oxysterol-binding protein-related protein 11
Constitutively active and highly phosphorylated on S-338, inhibited by PPP5C. Reduced kinase activity; when associated with 338-A-A-339. Constitutively active and non-inhibited by PPP5C; when associated with 338-D-E-339.
In CMD1NN; shows a mild increase in kinase activity.
In CMD1NN; shows impaired kinase activity and reduced MAPK3 activation with this mutation.
In NS5 and LPRD2; shows in vitro greater kinase activity and enhanced ERK activation than wild-type.
In NS5 and LPRD2; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type.
In NS5; has reduced or absent kinase activity.
In NS5; shows greater kinase activity and enhanced MAPK1 activation than wild-type.
In NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type.
In an ovarian serous carcinoma sample; somatic mutation; increased ERK activation.
In hypertrophic cardiomyopathy; unknown pathological significance.
Increased kinase activity but can still be inhibited by PPP5C; when associated with D-491.
Increased kinase activity but can still be inhibited by PPP5C; when associated with D-494.
Loss of methylation. Increased stability and catalytic activity in response to EGF treatment.
Non-inhibited by PPP5C. Constitutively active and non-inhibited by PPP5C; when associated with 340-D-D-341.
Phosphoserine; by PAK1, PAK2, PAK3 and PAK5
RAF proto-oncogene serine/threonine-protein kinase
Reduced kinase activity; when associated with 340-D-D-341.
Ubiquinone biosynthesis protein COQ9, mitochondrial
Calcium homeostasis endoplasmic reticulum protein
Found in a patient with intellectual disability, dysmorphic features, hypertension and diabetes; unknown pathological significance.
In SCA45; unknown pathological significance.
MTRF1L release factor glutamine methyltransferase
In PVNH8; decreased interaction with GGA3.
In PVNH8; unknown pathological significance.
Inhibits GTP hydrolysis. Coatomer proteins recruitment to the Golgi membrane and formation of coated vesicles are normal. However, Golgi transport is severely reduced due to impaired vesicle uncoating.
Decreases interaction with SH2D1A and INPP5D 2-fold, reduced T-cell response.
In COXPD34; results in decreased mitochondrial protein synthesis and reduced levels of respiratory complexes; MRPS7 mRNA and protein levels are reduced.
Increased chitinase activity; when associated with D-45 and M-61.
Increased chitinase activity; when associated with D-45 and N-47.
Increased chitinase activity; when associated with N-47 and M-61.
Loss of chitinase activity. No effect on protection against apoptosis or on AKT1 activation.
Acquires the capacity to efficiently repair N1-methyladenine adduct in dsDNA.
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3
Decreases activity against N1-methyladenine.
Decreases activity towards ssDNA by 25%. Loss of activity towards dsDNA.
Loss of activity against N1-methyladenine.
Strongly increases activity towards dsDNA, possibly by facilitating access to the active site.
In EXT2; no effect on oligomeric complex formation with EXT1.
In SSMS; decreased protein abundance; levels of the EXT2-interacting protein NDST1 are abolished in patient cells.
Zinc finger and SCAN domain-containing protein 18
Nutritionally-regulated adipose and cardiac enriched protein homolog
Slightly increased deconjugation activity.
NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2
Steroidogenic acute regulatory protein, mitochondrial
Transmembrane emp24 domain-containing protein 4
Impairs formation of heterotetramers with MAP2K1, but not the formation of heterodimers.
O-linked (Gal...) hydroxylysine; alternate
O-linked (Gal...) hydroxylysine; partial
In isoform 2, isoform 4, isoform 6 and isoform 7.
Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2
In MCPH23; impairs mitotic chromosome compaction.
>50% Reduction of wt heteromeric current; ratio of 1:1 and 1:1:2.
Abolishes currents without reducing channel protein expression.
Found in patients with benign familial infantile seizures; unknown pathological significance.
Has no statistically significant effect on the current or biophysical properties of the heteromeric channel.
In BFNS2; about 50% reduction of wild-type heteromeric current; ratio of 1:1; or 20%; ratio of 1:1:2.
In BFNS2; reduces the maximal heteromeric current by 40% with no alteration in voltage dependence of activation or deactivation kinetics.
In BFNS2; unknown pathological significance.
Potassium voltage-gated channel subfamily KQT member 3
Rare variant; found in a patient with rolandic epilepsy and additional features such as mild developmental delay and abnormal behavior; unknown pathological significance.
In CILD34; loss of expression in patient cells; increased proteasome-mediated degradation; no effect on homodimerization.
Protein transport protein Sec61 subunit gamma
No effect on ceramide hydrolase activity.
28S rRNA (cytosine-C(5))-methyltransferase
Abolished methyltransferase activity without affecting nucleolar localization; when associated with S-308.
Abolished methyltransferase activity without affecting nucleolar localization; when associated with S-359.
C2 calcium-dependent domain-containing protein 4B
In BSVD1; associated with ocular anomalies of variable severity in some patients.
In BSVD1; diffuse small vessel disease of the brain associated with Axenfeld-Rieger anomaly and leukoencephalopathy.
In HANAC; requires 2 nucleotide substitutions.
In ICH; the mutant protein is retained intracellularly and is not secreted normally.
In isoform 2, isoform 3, isoform 5 and isoform 9.
Found in a patient with Joubert syndrome also carrying a deletion in MKS1 intron 15 and a missense mutation in TCTN3 gene 'P-95'; unknown pathological significance.
In MKS1; no rescue of ciliation defects in an MKS1-knockdown cell line.
In MKS1; unknown pathological significance.
In MKS1; unknown pathological significance; decreased primary cilia formation in starved fibroblasts from a patient also carrying a mutation potentially affecting splicing; complete rescue of ciliation defects in an MKS1-knockdown cell line; no effect on the localization to the transition zone.
In MKS1; unknown pathological significance; no defect of primary cilia formation in starved fibroblasts from a patient also carrying E-317; no effect on the localization to the transition zone.
In MKS1; unknown pathological significance; no defect of primary cilia formation in starved fibroblasts from a patient also carrying a deletion of S-372; no effect on the localization to the transition zone.
In MKS1; unknown pathological significance; no effect on primary cilia formation in starved fibroblasts from a patient also carrying a mutation creating a frameshift and a premature stop codon; partial rescue of ciliation defects in an MKS1-knockdown cell line; no effect on the localization to the transition zone.
Complete loss of SCFA-induced G protein-coupled receptor activity.
Complete loss of acetate-induced G protein-coupled receptor activity.
No effect on SCFA-induced G protein-coupled receptor activity.
Partial loss of SCFA-independent constitutive G protein-coupled receptor activity.
Partial loss of SCFA-induced G protein-coupled receptor activity.
Partial loss of propionate-induced G protein-coupled receptor activity.
In FGS4; does not reveal significant alterations induced by the mutation substitution; causes a partial skipping of exon 2 of the protein.
Probable disease-associated variant found in a patient with epilepsy and pontocerebellar hypoplasia.
UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 7
In PKDYS1; loss of dopamine:sodium symporter activity.
N-acetylthreonine; in Ragulator complex protein LAMTOR4, N-terminally processed
Ragulator complex protein LAMTOR4, N-terminally processed
In HPC2; does not affect the enzymatic activity.
In HPC2; higher frequency in prostate cancer cases.
In HPC2; risk factor for disease development; does not affect the enzymatic activity.
Decreases interaction with histone H3K4me0.
In isoform 2, isoform 3, isoform 4, isoform 6, isoform 9, isoform 12, isoform 13, isoform 14, isoform 15, isoform 16, isoform 21, isoform 22 and isoform 23.
In isoform 5, isoform 14, isoform 15, isoform 16, isoform 17, isoform 18, isoform 20, isoform 21 and isoform 23.
In isoform 5, isoform 7, isoform 8, isoform 10, isoform 12, isoform 13, isoform 14, isoform 15, isoform 16, isoform 17, isoform 18 and isoform 22.
In isoform 6, isoform 7, isoform 8, isoform 9, isoform 11, isoform 13, isoform 16, isoform 19, isoform 22 and isoform 23.
Increases interaction with histone H3K4me0.
Loss of binding to DBN1. Loss of cytoplasmic localization.
Abolishes plasma membrane targeting and nuclear localization.
Decreases plasma membrane targeting and nuclear localization.
In isoform 1b, isoform 1d, isoform 2b and isoform 2d.
In isoform 1c, isoform 1d, isoform 2c and isoform 2d.
In isoform 2a, isoform 2b, isoform 2c and isoform 2d.
Oxysterol-binding protein-related protein 3
Reduces VAPA binding. Abolishes association with endoplasmic reticulum.
28S ribosomal protein S25, mitochondrial
In COXPD50; severe reduction of MRPS25 protein levels resulting in destabilization of the entire small ribosomal subunit and a decrease of mitochondrial translation rate; causes oxidative phosphorylation defects in patient cells.
Does not affect interaction with histone H3.
Impairs interaction with histone H3. Reduces association to chromatin. Does not rescued histone H3 'Lys-79' dimethylation (H3K79me2) levels in MLLT10-depleted cells. Does not rescued DOT1L-target genes in MLLT10-depleted cells.
STE20/SPS1-related proline-alanine-rich protein kinase
Associated with S-409 in a MPS4A patient.
In MPS4A; associated with M-67 in a patient.
In MPS4A; mild/intermediate/severe form.
In MPS4A; mild/severe/intermediate form.
In MPS4A; severe form; common mutation; found in patients with Irish-British ancestry.
Tumor necrosis factor receptor superfamily member 6B
Loss of phosphorylation, no loss of interaction with PPP3CA and PPP3R1, reduced ability to inhibit calcineurin and increased protein half-life; alone or when associated with A-163.
Loss of phosphorylation, no loss of interaction with PPP3CA and PPP3R1, reduced ability to inhibit calcineurin and increased protein half-life; alone or when associated with A-167.
No loss of phosphorylation and no effect on protein half-life; alone or when associated with E-163.
No loss of phosphorylation and no effect on protein half-life; alone or when associated with E-167.
No effect on microtubule localization and MAPRE1 binding; when associated with 373-N-N-374.
No effect on microtubule localization and MAPRE1 binding; when associated with 461-N-N-462.
17-beta-hydroxysteroid dehydrogenase type 2
Processed cysteine-rich motor neuron 1 protein
Decreased metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Decreased metalloendopeptidase activity without effect on protein stability.
In SCAR30; decreased function in degradation of amyloid-beta protein 40; decreased metalloendopeptidase activity towards different substrates including an amyloid-beta peptide derivative; decreased protein levels in patient tissues; no effect on mitochondrial localization.
In SCAR30; strongly decreased metalloendopeptidase activity towards amyloid-beta protein 40 and amyloid-beta protein 42.
Loss of localization to the mitochondrion.
Loss of metalloendopeptidase activity towards an amyloid-beta peptide derivative.
Loss of metalloendopeptidase activity. Loss of activity towards an amyloid-beta peptide derivative.
No effect on metalloendopeptidase activity towards an amyloid-beta peptide derivative.
No loss of metalloendopeptidase activity under oxidizing conditions.
Loss of function; when associated with A-132; A-136; A-145; A-148; A-149; A-221 and A-224.
Loss of function; when associated with A-132; A-136; A-145; A-148; A-149; A-221 and A-225.
Loss of function; when associated with A-132; A-136; A-145; A-148; A-149; A-224 and A-225.
Loss of function; when associated with A-132; A-136; A-145; A-148; A-221; A-224 and A-225.
Loss of function; when associated with A-132; A-136; A-145; A-149; A-221; A-224 and A-225.
Loss of function; when associated with A-132; A-136; A-148; A-149; A-221; A-224 and A-225.
Loss of function; when associated with A-132; A-145; A-148; A-149; A-221; A-224 and A-225.
Loss of function; when associated with A-136; A-145; A-148; A-149; A-221; A-224 and A-225.
Zinc-regulated GTPase metalloprotein activator 1C
Loss of enzymatic activity, no loss of B3GNT8-binding.
N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2
Leucine-rich repeat and fibronectin type-III domain-containing protein 4
In mtEFHD1; abolished ability to enhance mitoflash activity; when associated with A-103; A-139 and K-150.
In mtEFHD1; abolished ability to enhance mitoflash activity; when associated with A-103; K-114 and A-139.
In mtEFHD1; abolished ability to enhance mitoflash activity; when associated with A-103; K-114 and K-150.
In mtEFHD1; abolished ability to enhance mitoflash activity; when associated with K-114; A-139 and K-150.
B-cell CLL/lymphoma 7 protein family member A
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-149 and D-152.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-149 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-138, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-137, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-130, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-127, D-137, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-123, D-130, D-137, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-116, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-115, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Marked reduction in RAC1-binding, loss of increase in RAC1 activity and of dorsal ruffles formation in response to PDGF treatment; when associated with D-116, D-123, D-127, D-130, D-137, D-138, D-139, D-145, D-148, D-149, D-152 and D-157.
Psoriasis susceptibility 1 candidate gene 1 protein
Non-structural maintenance of chromosomes element 1 homolog
UDP-glucose:glycoprotein glucosyltransferase 1
In MYP21; unknown pathological significance.
Protein-lysine methyltransferase METTL21C
Does not inhibit apolipoprotein B secretion.
Does not inhibit triglyceride transfer activity and apolipoprotein B secretion.
Does not inhibit triglyceride transfer activity.
In ABL; does not reduce interaction with P4HB/PDI and APOB; inhibits triglyceride transfer activity.
In ABL; no loss on localization to the endoplasmic reticulum; does not reduce interaction with APOB; inhibits interaction with P4HB/PDI; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein B secretion.
In ABL; no loss on localization to the endoplasmic reticulum; does not reduce interaction with P4HB/PDI; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein B secretion.
In ABL; no loss on localization to the endoplasmic reticulum; inhibits triglyceride transfer activity.
In ABL; no loss on localization to the endoplasmic reticulum; reduces interaction with P4HB/PDI; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein B secretion.
In ABL; unknown pathological significance; does not reduce interaction with P4HB/PDI and APOB; does not reduce triglyceride transfer activity.
In ABL; unknown pathological significance; does not reduce interaction with P4HB/PDI and APOB; reduces triglyceride transfer activity.
Inhibits triglyceride transfer activity.
Microsomal triglyceride transfer protein large subunit
No loss on localization to the endoplasmic reticulum and does not reduce interaction with APOB or P4HB/PDI, does partially reduce phospholipid or triglyceride transfer activity and apolipoprotein B secretion.
No loss on localization to the endoplasmic reticulum and does not reduce interaction with APOB, but inhibits interaction with P4HB/PDI, phospholipid or triglyceride transfer activity and apolipoprotein B secretion.
No loss on localization to the endoplasmic reticulum, does not reduce interaction with APOB or P4HB/PDI, partially inhibits triglyceride transfer activity, does not inhibit phospholipid transfer activity and apolipoprotein B secretion.
No loss on localization to the endoplasmic reticulum. Does not inhibit triglyceride transfer activity.
No loss on localization to the endoplasmic reticulum. Inhibits triglyceride transfer activity.
No loss on localization to the endoplasmic reticulum; does not reduce interaction with P4HB/PDI; reduces phospholipid or triglyceride transfer activity; does not inhibit apolipoprotein B secretion.
Strongly reduces triglyceride transfer activity.
Calcium-binding and spermatid-specific protein 1
POU domain, class 3, transcription factor 2
Found in a male with undermasculinised genitalia and intra-abdominal testes; unknown pathological significance.
In PAPPAS; also responsible for ischiocoxopodopatellar syndrome in heterozygous carriers; no detectable protein expression in homozygous patient cells.
Loss of geranylgeranylation and association to membranes. Loss of interaction with NS5A, PIK3R1 and PIK3R2. No effect on interaction with PTPN13.
In IDD; requires 2 nucleotide substitutions.
Catalytically inactive. Unable to autocleave procathepsin L.
Found in patients with orofacial clefting; unknown pathological significance.
In allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4.
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform
Partial loss of sumoylation. Almost complete loss of sumoylation, partial loss of transcription repression, no effect on subcellular location, loss of rDNA silencing; when associated with R-20.
Partial loss of sumoylation. Almost complete loss of sumoylation, partial loss of transcription repression, no effect on subcellular location, loss of rDNA silencing; when associated with R-512.
Abolishes integrin-mediated interaction with BCAR1 and BCAR3 and reduces interaction between BCAR1 and CRK and, BCAR1 and SRC. Abolishes integrin-induced SRC-mediated tyrosine phosphorylation of BCAR1. Abolishes integrin-mediated recruitment of BCAR1, BCAR3, CRK and PTPRA to focal adhesions. Reduces integrin-mediated activation and membrane recruitment of RAC1 and CDC42.
Receptor-type tyrosine-protein phosphatase alpha
Abolishes BCL10-mediated but not RIPK2-mediated ubiquitination. Important decrease in the ubiquitination level; when associated with R-285. No change in the ubiquitination level; when associated with R-115 or R-224.
Abolishes MARCH2F-mediated K48-linked ubiquitination and subsequent suppression of antiviral and antibacterial innate immune response.
Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity.
Complete loss of cleavage by HAV protease 3c.
Decreases ubiquitination and abolishes nuclear export.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin and interchain with MARCHF2)
Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation.
Greatly impairs tandem ubiquitin binding.
Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329.
Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336.
Important decrease in the ubiquitination level; when associated with R-399.
In EDAID1; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding.
In IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation.
In IMD33; impairs tandem ubiquitin binding.
In IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation.
In IP; only 46.3% of the activation obtained with the wild-type protein.
In IP; shows the same luciferase activity as the control.
MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked).
No change in the ubiquitination level; when associated with R-399.
No effect on MARCH2F-mediated K48-linked ubiquitination.
No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation.
Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. No effect on MARCH2F-mediated K48-linked ubiquitination.
Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309.
In MCPH19; unknown pathological significance.
Decreased uridine transport. Normal localization to the cell membrane.
Lower concentrative capacity and altered sodium binding capacity.
Reduced transport of inosine and thymidine.
Interchain (between non-catalytic and catalytic chains)
Transmembrane protease serine 11D catalytic chain
Transmembrane protease serine 11D non-catalytic chain
Loss of FURIN-mediated proteolytic processing in HEK293 cells, however processing in HL1 cells, likely mediated by CORIN, is only slightly reduced. Loss of CORIN-mediated processing in HL1 cells; when associated with A-102 and A-105.
Loss of FURIN-mediated proteolytic processing in HEK293 cells, however processing in HL1 cells, likely mediated by CORIN, is only slightly reduced. Loss of CORIN-mediated processing in HL1 cells; when associated with A-99 and A-105.
No effect on proteolytic processing in HEK293 or HL1 cells. Loss of CORIN-mediated processing in HL1 cells; when associated with A-99 and A-102.
Prevents O-glycosylation at this residue. Decreased extracellular levels of NPPB due to decreased stability after secretion whereas extracellular levels of brain natriuretic peptide 32 is increased. In HEK293 cells, proteolytic processing by CORIN or FURIN is reduced but in HL1 cells proteolytic processing is not affected.
Signal transducer and activator of transcription 5A
In isoform 2, isoform 3, isoform 5, isoform 6, isoform 7 and isoform 8.
Does not affect IL6 induced phosphorylation. Does not affect the interaction with SYK.
Does not affect the interaction with SYK.
Germinal center-associated signaling and motility protein
Prevents IL6 induced phosphorylation. Does not affect the interaction with SYK.
Abolishes repression by activated ErbB2/ErbB3; when associated with D-105.
Abolishes repression by activated ErbB2/ErbB3; when associated with D-87.
Enhances repression by activated ErbB2/ErbB3; when associated with A-105.
Enhances repression by activated ErbB2/ErbB3; when associated with A-87.
Found in a patient with a 46,XY disorder of sex development; unknown pathological significance; no change in positive regulation of DNA-binding transcription factor activity.
Found in a patient with a 46,XY disorder of sex development; unknown pathological significance; shows a higher positive regulation of DNA-binding transcription factor activity.
Found in a patient with a 46,XY disorder of sex development; unknown pathological significance; shows increased positive regulation of DNA-binding transcription factor activity.
In ODG8; completely inactive in positive regulation of DNA-binding transcription factor activity.
In IDDM20; decreased function in positive regulation of DNA-templated transcription.
In MODY3; abolishes interaction with PCBD1 and DNA.
In MODY3; no effect on interaction with PCBD1 and DNA.
In MODY3; reduces transcription activation by about 50%.
In MODY3; reduces transcription activation by about 80%.
In NIDDM; loss of function in positive regulation of DNA-templated transcription.
In a black African with an atypical form of diabetes; also in an individual with hepatic adenoma and familial early-onset diabetes.
In a hepatic adenoma sample; somatic mutation.
In a hepatic multiple adenoma sample; somatic mutation.
In a hepatocellular carcinoma sample; somatic mutation.
In late-onset NIDDM; also in an individual with hepatic hyperplasia and familial early-onset diabetes.
In late-onset NIDDM; low penetrance; unknown pathological significance.
No significant effect on transcription activation.
Reduces transcription activation by 70%.
Reduces transcription activation by 75%.
Strong association with NIDDM susceptibility; unique to the Canadian Oji-Cree population.
Cerebellar degeneration-related protein 2-like
Reduces guanine exchange factor activity by over 90%.
In PRAAS3; decreased protein maturation; changed proteasome assembly; poor incorporation into 20S and 26S proteasomes.
In PRAAS3; digenic inheritance; patient also carries a mutation in PSMB8; no effect on protein abundance; changed proteasome assembly; poor incorporation into 20S and 26S proteasomes.
Restores G(i) alpha binding and GDI activity of the GoLoco 2 domain.
A disintegrin and metalloproteinase with thrombospondin motifs 18
Probable inactive ribonuclease-like protein 13
In HSCR4; risk factor associated with disease susceptibility.
Probable ATP-dependent RNA helicase DDX20
Abolishes interaction with RNA polymerase II complex subunits; when associated with A-100.
Abolishes interaction with RNA polymerase II complex subunits; when associated with A-105.
Abolishes interaction with RNA polymerase II complex subunits; when associated with A-136.
Abolishes interaction with RNA polymerase II complex subunits; when associated with A-140.
Putative RNA polymerase II subunit B1 CTD phosphatase RPAP2
Calcium-independent phospholipase A2-gamma
Loss of polyubiquitination of PCNA. Impairs interaction with SHPRH.
Leucine zipper putative tumor suppressor 3
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1
Almost completely abolishes nuclear localization.
Causes conformational change of N-terminal residues and decreased sensitivity towards AMP with lack of conversion to the inactive T-state in the presence of AMP.
Greatly reduces affinity towards Ca(2+) and slightly reduces affinity towards Mg(2+).
Greatly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
In CORLK; decreased activity; decreased sensitivity to allosteric inhibition by AMP; decreased thermal stability.
Minor reduction in nuclear localization.
No effect on kinetic properties and interaction with ALDOA.
No effect on kinetic properties but decreases binding to ALDOA.
Reduces sensitivity to AMP; when associated with E-21 and C-180.
Reduces sensitivity to AMP; when associated with E-21 and M-178.
Reduces sensitivity to AMP; when associated with M-178 and C-180.
Reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
Significantly reduces nuclear localization.
Slightly reduces sensitivity to inhibition by AMP and Ca(2+) and activation by Mg(2+). Decreases binding to ALDOA.
Splicing regulatory glutamine/lysine-rich protein 1
Abolishes autocleavage; when associated with A-1161 and A-1210.
Abolishes autocleavage; when associated with A-1161 and A-1281.
Abolishes autocleavage; when associated with A-1181 and A-1210.
Abolishes autocleavage; when associated with R-1178; E-1181; R-1207 and E-1210. Does not affect the protease function.
Abolishes phosphorylation at this site, as well as the negative regulation due to phosphorylation.
Does not affect autocleavage. Does not affect the protease function.
Strongly reduces autocleavage at this site, but enhances autocleavage at site 1. Does not affect the protease function.
Immunoglobulin lambda-like polypeptide 1
In DEE88; decreased protein expression; increased levels of glutamate and glycerol-3-phosphate.
Associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes; found in patients with Leber congenital amaurosis, Senior-Loken syndrome, Joubert syndrome and Bardet-Biedl syndrome; abrogates interaction with RPGR.
In JBTS7; affects interaction with NPHP4.
In JBTS7; also in a patient with Leber congenital amaurosis; affects interaction with NPHP4.
In JBTS7; seems not to affect interaction with NPHP4.
In a patient with Leber congenital amaurosis.
In a patient with Meckel-Gruber like syndrome also carrying L-220 and V-280 in TTC21B; also found in patients with Leber congenital amaurosis and a patient with Bardet-Biedl syndrome.
In patients with Leber congenital amaurosis.
In NPHS18; decreased function in nephrogenesis; unable to fully rescue morpholino-induced nephrogenesis defects in Xenopus.
In NPHS18; loss of function in nephrogenesis; unable to rescue morpholino-induced nephrogenesis defects in Xenopus.
In NPHS18; loss of function in nephrogenesis; unable to rescue morpholino-induced nephrogenesis defects in Xenopus; decreased interaction with NUP107.
Ras GTPase-activating-like protein IQGAP2
Cilia- and flagella-associated protein 418
Abolished delipidation by ATG4 family proteins.
Decreased interaction with Legionella effector RavZ.
Impaired localization to autophagosomes.
Increased interaction with WDFY3/ALFY, no effect on SQSTM1-binding; when associated with K-26 and D-57.
Increased interaction with WDFY3/ALFY, no effect on SQSTM1-binding; when associated with K-26 and Y-27.
Increased interaction with WDFY3/ALFY, no effect on SQSTM1-binding; when associated with Y-27 and D-57.
Microtubule-associated proteins 1A/1B light chain 3B
No processing of precursor. No lipidation. Decreases C18 ceramide binding.
Endogenous retrovirus group 3 member 1 Env polyprotein
In ATFB9; has a gain-of-function effect on the channels.
In LQT7; loss of function and dominant-negative effect in current.
In LQT7; loss of function mutation acting in a dominant-negative manner.
In LQT7; there is loss of function when the mutant is expressed alone and a dominant-negative effect when expressed with wild-type channels; channel trafficking and assembly are not affected.
Abolished binding to CLINT1. Abnormal subcellular localization restricted to late endosomes and lysosomes.
Abolished binding to CLINT1. Rescued binding to CLINT1 E-146 mutant.
Vesicle transport through interaction with t-SNAREs homolog 1B
Found in a patient with a severe neurological disorder; unknown pathological significance; reduced protein expression due to protein instability; protein misfolding; formation of nuclear puncta in some cells; loss of activation of HSPA1A, HSPA6 and DHRS2.
Reduced protein expression and formation of nuclear puncta in some cells.
Long-chain fatty acid transport protein 3
In HALP1; reduced secretion into plasma.
Reduces cholesteryl ester transfer by 60%.
Reduces triglyceride transfer 10-fold. No effect on cholesteryl ester transfer.
Reduces triglyceride transfer 10-fold. Slight reduction of cholesteryl ester transfer.
Reduces triglyceride transfer 5-fold. Slight reduction of cholesteryl ester transfer.
Reduces triglyceride transfer and cholesteryl ester transfer 5-fold.
Leukocyte immunoglobulin-like receptor subfamily A member 5
Fibronectin type III domain-containing protein 5
Histone-lysine N-trimethyltransferase SMYD5
Trafficking protein particle complex subunit 4
Increases ROS levels induced by neurotoxins.
Thioredoxin reductase-like selenoprotein T
Processed zona pellucida sperm-binding protein 4
Abolishes ability to ubiquitinate KDM4A.
Does not affect ability to bind ubiquitin and localization to DSBs sites, while it abolishes E3 ligase activity; when associated with S-16.
Does not affect ability to bind ubiquitin and localization to DSBs sites, while it abolishes E3 ligase activity; when associated with S-19.
Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes.
Does not affect ubiquitin-binding but impairs recruitment to DSBs.
Impairs ability to form foci following ionizing radiation and impaired binding to 'Lys-63'-linked ubiquitin.
Still able to bind 'Lys-63'-linked ubiquitin.
Mannosyl-oligosaccharide 1,2-alpha-mannosidase IB
Abolishes nuclear localization; when associated with 66-A-A-67.
Abolishes nuclear localization; when associated with 91-A-A-92.
In isoform 2A, isoform 2B and isoform 2C.
Nuclear receptor subfamily 1 group I member 2
Decreases the already low catalytic activity.
Increases activity with phosphotyrosine; when associated with A-105.
Increases activity with phosphotyrosine; when associated with V-107.
Abolishes BTK-mediated transcriptional activation. Abolishes BTK-mediated phosphorylation and impairs BTK-mediated transcriptional activation; when associated with F-248 and F-503.
Abolishes BTK-mediated transcriptional activation. Abolishes BTK-mediated phosphorylation and impairs BTK-mediated transcriptional activation; when associated with F-398 and F-503.
Impairs BTK-mediated transcriptional activation. Abolishes BTK-mediated phosphorylation and impairs BTK-mediated transcriptional activation; when associated with F-248 and F-398.
No change on BTK-mediated transcriptional activation.
In SKDEAS; unknown pathological significance.
In SKDEAS; unknown pathological significance; slightly decreased protein expression;.
CKLF-like MARVEL transmembrane domain-containing protein 5
Inter-alpha-trypsin inhibitor heavy chain H6
In JBTS3; alters interaction with HAP1 and NPHP1; loss of NPHP1AHI1(2):NPHP1(2) tetramers; loss of localization at cilium basal body and cell-cell junctions; loss of positive modulation of classical Wnt signaling; decreased interaction with CTNNB1.
In JBTS3; loss of localization at cilium basal body and cell-cell junctions.
In JBTS3; loss of localization at the primary cilium; loss of positive modulation of classical Wnt signaling; no effect on interaction with CTNNB1.
Pleckstrin homology domain-containing family F member 1
In SPGF56; unknown pathological significance.
Does not inhibit the interaction with TBCD and rescues the TBCD-induced microtubule destruction.
Does not inhibit the interaction with TBCD and rescues the TBCD-induced microtubule destruction. Reduces interaction with ARL2BP. Inhibits accumulation of STAT3 in the nucleus.
Does not reduce interaction with ARL2BP.
In MRCS1; decreased interaction with UNC119; decreased interaction with ARL2BP; changed cellular respiration; decreased ATP production.
Induces cell cycle arrest, reduces ability to form microtubules and centrosome fragmentation. Inhibits the interaction with TBCD and does not rescue the TBCD-induced microtubule destruction. Interacts with ARL2BP and PDE6D.
Reduces interaction with ARL2BP. Inhibits the interaction with TBCD and rescues the TBCD-induced microtubule destruction.
Loss of lactase activity. No effect on phlorizin hydrolase activity. No effect on localization to the plasma membrane.
No effect on lactase activity. Decreased phlorizin hydrolase activity. No effect on localization to the plasma membrane.
Nucleophile; for phlorizin hydrolase/Glycosylceramidase activity
Proton donor; for phlorizin hydrolase/Glycosylceramidase activity
Monocyte differentiation antigen CD14, membrane-bound form
Monocyte differentiation antigen CD14, urinary form
Causes dislocation from the centrosome; when associated with L-50.
Causes dislocation from the centrosome; when associated with L-59.
Putative aspartate aminotransferase, cytoplasmic 2
Decreases alpha-1,4-glucosidase activity toward long oligomaltose substrates having four to seven D-glucose residues.
Decreases alpha-1,4-glucosidase activity toward maltose.
Loss of alpha-1,4-glucosidase activity toward maltose.
Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase
In PAICSD; unknown pathological significance; no effect on protein abundance; decreased phosphoribosylaminoimidazole carboxylase activity; decreased phosphoribosylaminoimidazolesuccinocarboxamide synthase activity.
Loss of phosphoribosylaminoimidazole carboxylase activity.
No effect on phosphoribosylaminoimidazole carboxylase activity.
In CUGS; unknown pathological significance.
Prevents autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part.
Reduces autocatalytic cleavage and generation of Myelin regulatory factor, N-terminal part.
Delivered to both at the cell surface and in vesicles of melanocytic and non-melanocytic cells. Strongly delivered at the cell surface of melanocytic and non-melanocytic cells; when associated with 329-A-A-330.
In OA1; abnormal distribution of melanosomes; Not delivered at the cell surface of melanocytic and non-melanocytic cells.
In OA1; not delivered at the cell surface of melanocytic and non-melanocytic cells.
In OA1; results in altered glycosylation pattern and subcellular localization consistent with protein retention in the endoplasmic reticulum.
In OA1; results in altered glycosylation pattern and subcellular localization consistent with protein retention in the endoplasmic reticulum; lacks G protein-activation abilities.
Mostly delivered at the cell surface of melanocytic and non-melanocytic cells. Strongly delivered at the cell surface of melanocytic and non-melanocytic cells; when associated with 224-A-A-225.
lysosomal/melanosomal membrane localization signal
In early-onset obesity; Japanese population; loss of methylation and repressor activity.
In early-onset obesity; Japanese population; loss of repressor activity.
In early-onset obesity; Japanese population; slight decrease of repressor activity.
In early-onset obesity; Japanese population; strong decrease of repressor activity.
Nuclear receptor subfamily 0 group B member 2
Found in patient with Joubert syndrome; unknown pathological significance.
CLK4-associating serine/arginine rich protein
In DFNB36; irregular microvillar organization.
In DFNB36; severe phenotype; severe impairment of microvillar elongation; espin is less efficiently targeted to the microvilli and accumulates in the nucleus.
In DFNB36; sporadic case with mild phenotype; unknown pathological significance.
In USH1M; results in impaired elongation of microvilli and stereocilia consistent with a loss of function in parallel actin filament bundle assembly; retains localization to microvilli and stereocilia.
Loss of targeting to microvilli. Impaired microvillar elongation.
No effect on localization to microvilli. No effect on microvillar elongation.
Abolishes interaction with YWHAB; when associated with A-237.
Abolishes nuclear export; when associated with A-132.
Abolishes nuclear export; when associated with A-136.
Found in a patient with closed spina bifida; sporadic case; unknown pathological significance.
Found in a patient with craniorachischisis; sporadic case; unknown pathological significance.
Found in a patient with encephalocele; sporadic case; unknown pathological significance.
Impairs interaction with YWHAB. Abolishes interaction with YWHAB; when associated with A-827.
In NTD; does not affect interaction with DVL2; does not affect subcellular location; results in reduced RHOA and JNK activation.
In NTD; uncertain pathological significance; does not affect interaction with DVL2; does not affect subcellular location; increases RHOA activation but decreases the ability to activate JNK.
In TBS2; the mutant protein is stable and expressed.
Partial nuclear accumulation upon LMB treatment.
Coiled-coil domain-containing protein 80
In GAMOS7; decreased function in nephrogenesis; unable to fully rescue morpholino-induced nephrogenesis defects in Xenopus; decreased protein amount detected by Western blot in patient cells; affects exon 4 splicing resulting in decreased levels of wild-type mature transcript; impairs assembly of nuclear pore complex.
In GAMOS7; unknown pathological significance.
In NPHS11; decreased function in nephrogenesis; unable to fully rescue morpholino-induced nephrogenesis defects in Xenopus; decreased interaction with NUP133.
In NPHS11; decreased interaction with NUP133; changed localization to the nuclear pore with relocalization to the cytoplasm.
In NPHS11; no effect on interaction with NUP133; no effect on localization to the nuclear pore.
In NPHS11; unknown pathological significance.
Abolished association with the cell membrane, leading to impaired activation of receptor tyrosine kinase ALK.
Abolished interchain disulfide bond without affecting homodimerization.
Reduced affinity for receptor tyrosine kinases ALK and LTK.
Slightly reduced affinity for receptor tyrosine kinase LTK.
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform
YjeF N-terminal domain-containing protein 3
Almost complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with F-566.
Complete loss of PAK6 activation by MAP2K6/MAPKK6; when associated with A-165.
In SPGF38; unknown pathological significance.
Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein
Reduced tyrosine phosphorylation and reduced binding of SH2D1B. Loss of phosphorylation and loss of binding of SH2D1A and SH2D1B; when associated with F-279.
Reduced tyrosine phosphorylation, reduced binding of SH2D1B and loss of binding of SH2D1A.
MyoD family inhibitor domain-containing protein
Abolishes sumoylation. No change in nuclear location nor on protein stability. Increased AP1 transactivation activity when heterodimerized with cJUN.
Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-362.
Increased protein stability. Increased MOS/MAPK-mediated transforming ability and no change in sumoylation levels; when associated with D-374.
Loss of activation of phospholipid synthesis; when associated with E-10.
Loss of activation of phospholipid synthesis; when associated with E-30.
Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-374.
No change in sumoylation levels. Loss of protein stability. Reduced MOS/MAPK-mediated transforming ability; when associated with A-362.
No effect on Tyr-phosphorylation. Loss of endoplasmic reticulum localization in quiescent cells.
Overall loss of Tyr-phosphorylation, including that of Y-10 phosphorylation. Localizes to the endoplasmic reticulum in quiescent cells. Activates phospholipid synthesis in growing cells.
Overall loss of Tyr-phosphorylation, including that of Y-30 phosphorylation. Localizes to the endoplasmic reticulum in quiescent cells. Activates phospholipid synthesis in growing cells.
Phosphoserine; by MAPK1, MAPK3 and RPS6KA3
Ankyrin repeat domain-containing protein 55
Does not affect protein localization to Golgi apparatus. Prevents myristoylation in vitro.
In DMC; results in protein mis-localization and aggregation.
In SMC1; does not affect protein localization.
In ICF4; unknown pathological significance.
In ENS-MECP2; uncertain pathological significance.
In MRXS13; impairs interaction with ATRX and abolishes ATRX recruitment to heterochromatin.
In MRXS13; unknown pathological significance.
In RTT; abolishes interaction with TBL1X and TBL1XR1.
In RTT; abolishes interaction with TBL1X.
In RTT; also in a patient with Angelman syndrome and some typical RTT features.
In RTT; impairs interaction with ATRX and abolishes ATRX recruitment to heterochromatin.
In RTT; unknown pathological significance.
Probable disease-associated variant found in a patient with drug-resistant epilepsy with intellectual disability, parkinsonism and other neurologic symptoms.
In BLS; loss of sequence-specific DNA binding; loss of transcriptional activity.
In BLS; no effect on protein abundance; no effect on sequence-specific DNA binding; enhances transcriptional activity toward TG and TPO genes.
In BLS; without choanal atresia; no effect on protein abundance; no effect on localization to the nucleus; decreased sequence-specific DNA binding; decreased transcriptional activity.
In NMTC4; increased cell growth; increased cell migration; associated with increased expression of the WNT5A gene.
In congenital hypothyroidism; loss of sequence-specific DNA binding; loss of transcriptional activity.
In congenital hypothyroidism; slightly decreased sequence-specific DNA binding to the TPO promoter; 0.5 fold decreased transcriptional activity.
In congenital hypothyroidism; with absence of thyroid agenesis; loss of sequence-specific DNA binding; loss of transcriptional activity.
Abolishes interaction with PSMD4; when associated with A-9.
Abolishes interaction with PSMD4; when associated with T-49.
Impairs UBL-UBA domain interaction and enhances ubiquitin-binding; when associated with Glu-10.
Impairs UBL-UBA domain interaction and enhances ubiquitin-binding; when associated with Glu-47.
Impairs UBL-UBA domain interaction and enhances ubiquitin-binding; when associated with Glu-77.
Increases interaction with PSMD1 and PSMC1.
No effect on UBL-UBA domain interaction.
UV excision repair protein RAD23 homolog A
Deamidated glutamine; by Photorhabdus PAU_02230
Decreased affinity for CCDC88C and PLCD4.
Guanine nucleotide-binding protein G(i) subunit alpha-3
Increased affinity for PLCD4. No effect on binding to CCDC88C.
Disintegrin and metalloproteinase domain-containing protein 17
In NEDSSWI; decreased deoxyhypusine synthase activity.
In NEDSSWI; loss of deoxyhypusine synthase activity.
Loss of covalent intermediate formation and deoxyhypusine synthesis.
Reduces covalent intermediate formation and deoxyhypusine synthesis by 99.5%. Retains low spermidine cleavage activity.
Reduces spermidine binding by 98%. Loss of covalent intermediate formation and deoxyhypusine synthesis.
Reduces spermidine binding by 98%. Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate.
Reduces spermidine binding by 98%. Strongly reduced formation of covalent intermediate.
Strongly reduced NAD and spermidine binding. Reduced activity.
Strongly reduced NAD binding. No effect on enzyme activity.
Strongly reduced NAD binding. Strongly reduced activity.
Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate.
Strongly reduced spermidine binding. Reduced activity.
In OI5; correlates with reduced expression and barely detectable secretion of SERPINF1.
Interferon-induced transmembrane protein 5
Coiled-coil domain-containing protein 85A
ATP-dependent 6-phosphofructokinase, platelet type
Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe
In SCDO3; not localized to the correct compartment of the cell; unable to modulate Notch signaling in a cell-based assay; enzymatically inactive.
In DIAR4; attenuated NEUROG3 function in vivo.
Abolished GlcNAcylation by E.coli NleB1. Abolished ability to self-oligomerize. Strongly reduced GlcNAcylation by S.typhimurium Ssek1; when associated with A-245.
Strongly reduced GlcNAcylation by S.typhimurium Ssek1; when associated with A-235.
Tumor necrosis factor receptor type 1-associated DEATH domain protein
Leukocyte immunoglobulin-like receptor subfamily A member 2
Does not affect tyrosine phosphorylation; does not affect interaction with RASA1.
In CMAVM2; highly decreased tyrosine phosphorylation; highly decreased interaction with RASA1.
In CMAVM2; loss of tyrosine phosphorylation; loss of interaction with RASA1.
In CMAVM2; the mutant protein is not detected by Western blot; loss of localization to cell membrane.
In CMAVM2; unknown pathological significance.
Loss of catalytic activity. Fails to block TGF-beta-mediated anti-proliferative signal in tumor cells.
Mas-related G-protein coupled receptor member F
Decreased sterol transport; probable decreased expression due to nonsense-mediated decay.
Steroid transmembrane transporter SLC22A24
Induces a mild reduction in enzyme activity.
Does not abolish the effect on actin stress fibers but moderates its capability to induce membrane protrusions.
40S ribosomal protein S5, N-terminally processed
N-acetylmethionine; in 40S ribosomal protein S5; alternate
N-acetylthreonine; in 40S ribosomal protein S5, N-terminally processed
In POF7; without adrenal failure; partial loss of activity.
In SPGF8 and POF7; activity levels similar to wild-type.
In SPGF8; impairs transactivational activity.
In SRXY3 and SRXX4; decreased transactivator activity; loss of DNA binding, at least to some known consensus target sequences; no effect on nuclear location.
In SRXY3, SRXX4 and AINR; decreased transactivator activity; no effect on nuclear location.
In SRXY3; loss of DNA-binding; significantly decreased transactivator activity.
In SRXY3; without adrenal failure; markedly impaired transcriptional activity.
Loss of sumoylation; when associated with R-194.
Loss of transactivation; when associated with A-440.
Loss of transactivation; when associated with F-436.
Reduced transactivation. Strongly reduced transactivation; when associated with E-341.
Reduced transactivation. Strongly reduced transactivation; when associated with F-344.
Putative inactive deoxyuridine 5'-triphosphate nucleotidohydrolase-like protein FLJ16323
Interchain (between alpha-2-3 and delta-3 chains)
Voltage-dependent calcium channel subunit alpha-2-3
Voltage-dependent calcium channel subunit alpha-2/delta-3
Voltage-dependent calcium channel subunit delta-3
Protein phosphatase 1 regulatory subunit 1B
Abolishes dimerization; when associated with N-56; E-59 and 62-D-E-63.
Abolishes dimerization; when associated with S-54; E-59 and 62-D-E-63.
Abolishes dimerization; when associated with S-54; N-56 and 62-D-E-63.
Abolishes dimerization; when associated with S-54; N-56 and E-59.
Abolishes interaction with CHMP2A and assembly into helical tubes in vitro; when associated with D-59; D-168 and D-169.
Abolishes interaction with CHMP2A and assembly into helical tubes in vitro; when associated with D-62; D-168 and D-169.
Abolishes interaction with VPS4A and STAMBP.
Impairs HIV-1 release; when associated with 24-S-A-25.
Impairs HIV-1 release; when associated with S-28.
Impairs interaction with VPS4A and STAMBP.
Induces assembly with CHMP2A into helical tubes in vitro and slightly enhances inhibition of HIV-1 budding in vivo. Abolishes interaction with CHMP2A and assembly into helical tubes in vitro; when associated with D-59 and D-62.
Induces assembly with CHMP2A into helical tubes in vitro; when associated with D-48.
Induces assembly with CHMP2A into helical tubes in vitro; when associated with D-64. Enhances inhibition of HIV-1 budding in vivo; when associated with D-168 and D-169.
Ankyrin repeat and death domain-containing protein 1A
Acyl-coenzyme A synthetase ACSM2A, mitochondrial
Abolishes inhibition of LIRE1 retrotransposition.
Serine/threonine-protein phosphatase 1 regulatory subunit 10
In PCH7; reduced protein levels; decreased function in snRNA 3'-end processing.
Zinc finger SWIM domain-containing protein 1
Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B
Keratinocyte differentiation-associated protein
Not sumoylated; when associated with R-102 and R-228.
Not sumoylated; when associated with R-102 and R-281.
Not sumoylated; when associated with R-228 and R-281.
Plasminogen activator inhibitor 1 RNA-binding protein
Impairs preautophagosomal localization; when associated with T-242.
Impairs preautophagosomal localization; when associated with T-243.
In IDDSSA; altered autophagosome assembly shown in patient cells.
WD repeat domain phosphoinositide-interacting protein 2
28S ribosomal protein S18c, mitochondrial
Associated with a pro-atherogenic phenotype.
Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase
Drastically decreased ACBD3-binding. No effect on C10ORF76-, nor RAB11B-binding.
Drastically decreased C10ORF76- and RAB11B-binding. 6-fold increase in ACBD3-binding.
No effect on ACBD3-, C10ORF76-, nor RAB11B-binding.
Small decrease in C10ORF76-binding. No effect on ACBD3-, nor RAB11B-binding.
Associated with poor response to eculizumab in PNH patients.
Mitochondrial import inner membrane translocase subunit Tim29
In UCMD1; fibroblasts with the mutation assembled and secreted normal collagen VI microfibrils; cell adhesion of heterozygous Arg-284 fibroblasts is markedly decreased but can be rescued by the addition of normal collagen VI.
Probable disease-associated variant found in a patient with limb-girdle muscular dystrophy.
Cell cycle checkpoint control protein RAD9A
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-375 and A-380.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-375 and A-387.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-341; A-380 and A-387.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-328; A-375; A-380 and A-387.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-277; A-341; A-375; A-380 and A-387.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-272; A-328; A-341; A-375; A-380 and A-387.
Complete loss of phosphorylation and no loss of interaction with the 9-1-1 complex; when associated with A-277; A-328; A-341; A-375; A-380 and A-387.
In EORVA; decreased transcriptional activity and impaired nuclear localization.
Abolished lysine-myristoylation, leading to decreased localization to membranes.
Constitutively active. Inhibits filopodia formation and dendritic branching.
Constitutively inactivated. Fails to associate with membranes. Does not inhibit filopodia formation.
Reduced affinity for receptor tyrosine kinase LTK.
Protein phosphatase 1 regulatory subunit 14B
Abolishes binding to SRC. Does not abolish phosphorylation by SRC. Abolishes phosphorylation by SRC; when associated with F-228 and F-302.
Decreased binding to PTK2/FAK1; when associated with A-127.
Decreased binding to PTK2/FAK1; when associated with A-130.
Decreased binding to PTK2/FAK1; when associated with A-57.
Decreased binding to PTK2/FAK1; when associated with A-60.
Enhanced translation of mRNAs containing poly-A leaders.
In DEmut; abolishes association with the ribosome and ability to initiate the ribosome quality control (RQC).
N-acetylthreonine; in Guanine nucleotide-binding protein subunit beta-2-like 1, N-terminally processed
No effect on binding to SRC. Abolishes binding to PTK2/FAK1 and reduces cell adhesion and foci formation.
No effect on binding to SRC. Abolishes phosphorylation by SRC; when associated with F-228 and F-246.
No effect on binding to SRC. Does not abolish phosphorylation by SRC. Abolishes phosphorylation by SRC; when associated with F-246 and F-302.
Phosphothreonine; by viral VacV B1 kinase
Receptor of activated protein C kinase 1
Receptor of activated protein C kinase 1, N-terminally processed
Decreased enzyme activity with sphingomyelin and para-nitrophenylphosphorylcholine.
Decreased enzyme activity; when associated with E-271.
Decreased enzyme activity; when associated with E-343.
Ectonucleotide pyrophosphatase/phosphodiesterase family member 7
Loss of enzyme activity with sphingomyelin.
Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-146 and Q-168.
Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-121; Q-168 and Q-267.
Strongly reduces N-glycosylation and enzyme activity; when associated with Q-100; Q-146; Q-168 and Q-267.
Strongly reduces N-glycosylation and enzyme activity; when associated with Q-121; Q-146; Q-168 and Q-267.
Monocyte to macrophage differentiation factor 2
Sodium-dependent noradrenaline transporter
Abolishes interaction with ARRB2; when associated with A-302.
Abolishes interaction with ARRB2; when associated with A-332. Diminishes interaction with ARRB2.
Killer cell immunoglobulin-like receptor 2DL1
In NEDDFAC; unknown pathological significance.
Abolishes heterodimerization with RXRA, DNA binding and transactivation activity.
Abolishes heterodimerization with RXRA. No DNA binding.
No effect on heterodimerization with RXRA nor on DNA binding and transactivation activity.
No effect on heterodimerization with RXRA nor on DNA binding.
Peroxisome proliferator-activated receptor alpha
Prevents DNA binding but no effect on heterodimerization with RXRA.
Reduced heterodimerization with RXRA. Reduced DNA binding.
In XDAT; partially disrupts the interaction with ZFPM1.
In XDAT; severe impairment of ZFPM1 binding and erythroid differentiation in vitro.
In XDAT; stronger loss of affinity than of G-218-GATA1 for ZFPM1 and disturbed GATA1 self-association.
In XLTT; does not affect ZFPM1 binding; reduced affinity to palindromic GATA sites; supports erythroid maturation less efficiently than wild-type GATA1.
Increase of dissociation rate from bound DNA.
Putative cleavage and polyadenylation specificity factor subunit 4-like protein
Hydroxysteroid dehydrogenase-like protein 2
Found in a patient with congenital bilateral cataract; unknown pathological significance.
Found in a patient with congenital pediatric onset cataracts; unknown pathological significance.
Gly-cisPro motif, important for rejection of L-amino acids
In DEE64; also found in a patient with Rett syndrome-like phenotype.
In DEE64; decreased proteasomal degradation; does not affect interaction with CUL3.
In DEE64; reduced RHOBTB2 proteasomal degradation; does not affect interaction with CUL3.
Results in decreased interaction with CUL3.
Rho-related BTB domain-containing protein 2
Decreases the recruitment within caveola.
Markedly decreases the recruitment within caveola.
Abolished stearoylation in response to S.flexneri infection.
Does not affect stearoylation in response to S.flexneri infection.
Abolishes inhibition of cAMP production in response to melanocortin receptor stimulation.
May play a role in obesity in an age-dependent manner; apparently no effect on activity.
39S ribosomal protein L27, mitochondrial
Sperm acrosome membrane-associated protein 1
ATP synthase-coupling factor 6, mitochondrial
In HA-GPID; Strongly reduced glucose-6-phosphate isomerase activity.
In HA-GPID; severe form with neurological deficits; GPI Homburg.
In HA-GPID; unknown pathological significance.
In ARLIAK; severely decreased transport of succinate, 2-oxoglutarate and N-acetylaspartate.
In ARLIAK; unable to transport succinate, 2-oxoglutarate and N-acetylaspartate.
Carotenoid-cleaving dioxygenase, mitochondrial
Abolishes methylcytosine dioxygenase activity.
In BEFAHRS; decreases methylcytosine dioxygenase activity.
In BEFAHRS; unknown pathological significance; no effect on methylcytosine dioxygenase activity.
In CEP; frequent mutation in Western countries; severe phenotype; loss of enzymatic activity, when tested in vitro.
In CEP; less than 2% wild-type activity.
In CEP; less than 5% wild-type activity.
In CEP; loss of enzymatic activity, when tested in vitro.
In CEP; mild phenotype; high residual activity.
In CEP; mild phenotype; less than 2% wild-type activity.
In CEP; mild phenotype; strong decrease in enzymatic activity, when tested in vitro; may affect thermal stability.
In CEP; moderately-severe phenotype; less than 2% wild-type activity.
In CEP; severe cutaneous lesions; less than 3% wild-type activity.
In CEP; severe phenotype; no detectable activity.
In CEP; the effect on catalytic activity is controversial.
1-aminocyclopropane-1-carboxylate synthase-like protein 1
Leucine-rich repeat-containing protein 14
Protein phosphatase 2C-like domain-containing protein 1
In GCLEB; enhanced autocatalytic cleavage.
In KCS2; enhanced autocatalytic cleavage.
In PIPmt; affects subcellular localization. Impaired PCNA stability and chromatin binding. Does not affect protease activity.
Strongly decreased single-stranded DNA-binding.
Defects in GTP hydrolysis. Does not affect the interaction with VAMP8 in response to starvation. Does not affect the interaction with TMED10.
Defects in GTP-binding. Abolishes the interaction with VAMP8 in response to starvation. Abolishes the interaction with TMED10.
In DEE100; unknown pathological significance.
Neuronal acetylcholine receptor subunit beta-3
Class E basic helix-loop-helix protein 40
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3)
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1, SUMO2 and SUMO3); alternate
Loss of interaction with BMAL1 and E-box binding. Significant reduction in its repressor activity against the CLOCK-BMAL1 heterodimer.
Loss of repressor activity against NR0B2.
No effect on its interaction with BMAL1 or its repressor activity against the CLOCK-BMAL1 heterodimer. Significant reduction in E-box binding.
No loss of repressor activity against NR0B2.
Partial loss of sumoylation. Complete loss of sumoylation; when associated with R-159.
Partial loss of sumoylation. Complete loss of sumoylation; when associated with R-279.
Complete loss of SIAH1-mediated degradation.
Complete loss of nuclear sublocalization.
Fails to influence alternative splicing of CD44, NRXN2 and NRXN3.
KH domain-containing, RNA-binding, signal transduction-associated protein 3
Probable polypeptide N-acetylgalactosaminyltransferase 8
Coenzyme Q-binding protein COQ10 homolog B, mitochondrial
Catechol O-methyltransferase domain-containing protein 1
Leucine-rich repeat-containing protein 15
Does not affect myristoylation; when associated with A-4. Loss of myristoylation; when associated with A-2. Loss of palmitoylation; when associated with A-4. Reduces cell membrane localization.
Does not affect myristoylation; when associated with A-8. Loss of myristoylation; when associated with A-2. Loss of palmitoylation; when associated with A-8. Reduces cell membrane localization.
In a cancer; unknown pathological significance.
Loss of CAND1-, CUL1-, CUL3- and RBX1-binding. Loss of function of inhibition of DCUN1D1-mediated CUL1 neddylation, but no effect on localization at the cell membrane; when associated with N-241 and N-271. Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5, CAND1 and RBX1; when associated with A-241 and A-271. Does not affect both nucleus and cytoplasm localization; when associated with A-241 and A-271. Loss of interaction with CUL3; when associated with A-241 and A-271.
Loss of CAND1-, CUL1-, CUL3- and RBX1-binding. Loss of function of inhibition of DCUN1D1-mediated CUL1 neddylation, but no effect on localization at the cell membrane; when associated with N-241 and R-265.
Loss of CAND1-, CUL1-, CUL3- and RBX1-binding. Loss of function of inhibition of DCUN1D1-mediated CUL1 neddylation, but no effect on localization at the cell membrane; when associated with R-265 and N-271.
Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CALD1 and RBX1; when associated with A-241 and R-265. Does not affect both nucleus and cytoplasm localization; when associated with A-241 and R-265. Loss of interaction with CUL3; when associated with A-241 and A-271.
Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5, CAND1 and RBX1; when associated with R-265 and A-271. Does not affect both nucleus and cytoplasm localization; when associated with R-265 and A-271. Loss of interaction with CUL3; when associated with R-265 and A-271.
No effect on CAND1-, CUL1-, CUL3- and RBX1-binding.
No effect on CAND1-, CUL1-, CUL3- and RBX1-binding. Loss of localization at the cell membrane. Loss of function of inhibition of DCUN1D1-mediated CUL1 neddylation. Loss of myristoylation. Loss of myristoylation; when associated with A-4. Loss of myristoylation; when associated with A-8. Loss of palmitoylation. Affects cell membrane localization, and localizes throughout the cytoplasm. Does not relocalizes CUL3 to the cell membrane.
Does not affect level of auto-AMPylation.
Slightly decreased N-glycosylation. Abolished N-glycosylation; when associated with Q-275.
Strongly decreased N-glycosylation. Abolished N-glycosylation; when associated with Q-446.
In CANDF8; abolishes homotypic interactions with the SEFIR domain of IL17RA, IL17RB and IL17RC; does not affect homodimerization; does not affect SEFIR-independent interactions with other proteins.
In PSORS13; there is a reducing binding of this variant to TRAF6.
Abolishes interaction with U4 snRNA. Abolishes interaction with the 7-methylguanosine cap of RNA molecules. No effect on interaction with SMN complex.
Abolishes interaction with U4 snRNA. No effect on interaction with the isolated 7-methylguanosine cap that is normally part of RNA molecules. No effect on interaction with 80S ribosomes.
Abolishes interaction with the isolated 7-methylguanosine cap that is normally part of RNA molecules.
In NEDCAM; impaired function in spliceosomal snRNP assembly; decreased protein abundance; decreased protein stability; decreased interaction with DDX20; decreased interaction with GEMIN4.
In NEDCAM; unknown pathological significance.
No effect in interaction with U4 snRNA. No effect on interaction with SMN complex.
Strongly decreases interaction with U4 snRNA. No effect on interaction with the isolated 7-methylguanosine cap that is normally part of RNA molecules. Abolishes interaction with 80S ribosomes.
Abolishes location at the cell membrane; when associated with A-663 and A-675.
Abolishes location at the cell membrane; when associated with A-675 and 722-A--A-729.
Loss of translocation to sites of contact between the endoplasmic reticulum and the cell membrane.
No effect on translocation to sites of contact between the endoplasmic reticulum and the cell membrane.
EARP and GARP complex-interacting protein 1
Decreases androsterone dehydrogenase activity; when associated with F-176.
Decreases androsterone dehydrogenase activity; when associated with R-180.
Abolishes change in ion selectivity in the presence of subphysiological K(+) levels.
Abolishes channel activity and formation of disulfide-linked homodimers.
Converts the electrically silent channel that is present at the cell membrane to an active channel.
Converts the electrically silent channel that is present at the cell membrane to an active channel. No effect on retention in recycling endosomes.
Decreases channel activity and abolishes inhibition by acidification of the extracellular medium.
Does not increase the low intrinsic channel activity.
Impairs selectivity for K(+) ions and increases permeability to Na(+) ions, both at pH 7.4 and at pH 6.
Increases channel activity, and has only a minor effect on the inhibition by acidification of the extracellular medium.
Increases channel activity. Strongly increases channel activity; when associated with S-146.
Increases channel activity. Strongly increases channel activity; when associated with S-261.
No effect on intracellular retention in recycling endosomes.
Slightly decreases the increased permeability to Na(+) ions at pH 6.
Strongly decreases activity of homodimeric channels and of heterodimeric channels formed with KCNK3 and with KCNK9. No effect on location at the cell membrane.
Strongly increases location at the cell membrane.
Abolishes interaction with S-adenosyl-L-methionine.
Confers a WRAD-dependent gain-of-function histone H3 dimethylation activity. Converts H3K4me1 into H3K4me2.
Loss of polyisoprenoid diphosphate phosphatase activity.
Polyisoprenoid diphosphate/phosphate phosphohydrolase PLPP6
Kelch repeat and BTB domain-containing protein 2
Abolished protein-lysine deacetylase activity in vitro.
Putative protein-lysine deacylase ABHD14B
Kazal-type serine protease inhibitor domain-containing protein 1
In OFD5; markedly reduced expression in fibroblasts compared to wild-type protein; impaired SHH signaling in SAG-treated fibroblasts.
Probable ATP-dependent RNA helicase DDX59
Loss of interaction with ANK3. Intracellular retention; when associated with A-420 and A-421.
Partial loss of interaction with ANK3. Intracellular retention; when associated with A-419 and A-420.
Partial loss of interaction with ANK3. Intracellular retention; when associated with A-419 and A-421.
Associated with exfoliation syndrome in the presence of D-153.
Associated with exfoliation syndrome in the presence of L-141.
Lysine tyrosylquinone (Lys-Tyr); alternate
In POF2B; disrupts binding to nonmuscle actin filaments; abolishes tight junction localization; altered ciliogenesis and cystogenesis.
Disrupt trimer formation, 50-fold reduction in E3 ligase activity.
In AS; unknown pathological significance.
In DEEAH and NEDDISH; unknown pathological significance.
In DEEAH; impaired TNFA-induced activation of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-induced apoptosis; decreased EGF internalization.
In DEEAH; unknown pathological significance.
In NEDDISH; impaired TNFA-induced activation of the MAP kinases ERK1/2; enhanced susceptibility to TNFA-induced apoptosis; decreased EGF internalization.
In NEDDISH; unknown pathological significance.
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6 and isoform 8.
In isoform 3, isoform 5, isoform 6 and isoform 8.
In isoform 4, isoform 5, isoform 6 and isoform 8.
MAP kinase-activating death domain protein
Abolishes binding to heparin, lipid A, lysozyme and DNA.
Associated with lower plasma lactoferrin concentrations.
Decreased antibacterial activity against Gram-positive bacteria; seems to reduce susceptibility to localized juvenile periodontitis; associated with increased plasma lactoferrin concentrations and possibly with susceptibility to coronary artery stenosis.
Destabilizes iron binding significantly.
Disrupts anion binding site and destabilizes iron binding.
Greatly impairs binding to heparin, lipid A, lysozyme and DNA. Impairs antibacterial activity.
Impairs binding to heparin, lipid A, lysozyme and DNA.
Impairs iron binding and changes domain closure.
In TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity.
In TAM1; increased calcium-dependent susceptibility to proteolytic degradation; decreased calcium-dependent aggregation; decreased calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; no effect of the ability to inhibit store-operated calcium entry (SOCE) activity; muscle fibers with the mutation have significantly decreased calcium-dependent sensitivity to caffeine.
In TAM1; no effect on calcium-dependent susceptibility to proteolytic degradation; increased moderately calcium-dependent aggregation; increased moderately calcium-dependent polymerization; no effect on subcellular localization; no effect on the subcellular localization of STIM1; decreased calcium content of intracellular stores; loss of the ability to inhibit store-operated calcium entry (SOCE) activity.
In VMCQA; no effect on calcium-dependent susceptibility to proteolytic degradation; increased calcium-dependent aggregation; causes impaired polymerization of the protein; no effect on subcellular localization; decreased calcium content of sarcoplasmic reticulum stores; reduced sarcoplasmic reticulum calcium release during excitation-contraction coupling.
ATP-binding cassette sub-family C member 5
SLIT-ROBO Rho GTPase-activating protein 3
Chromatin modification-related protein MEAF6
In PC deficiency; mild; strongly reduced pyruvate carboxylase activity.
Loss of tetramerization and enzyme activity, resulting in an inactive homodimer.
Abolished cleavage by granzyme A (GZMA), preventing release of the N-terminal moiety (Gasdermin-B, N-terminal) and ability to induce pyroptosis in target cells of cytotoxic T-cells and natural killer (NK) cells.
Does not prevent cleavage by granzyme A (GZMA).
Alters substrate specificity of group B transferase.
Alters substrate specificity so that both UDP-N-acetyl-D-galactosamine and UDP-galactose are utilized.
Decreases specific activity of group B transferase almost to zero.
Fucosylglycoprotein alpha-N-acetylgalactosaminyltransferase soluble form
Histo-blood group ABO system transferase
In allele Bel01; loss of manganese binding and reduced catalytic activity.
In group B transferase; lower-level protein expression and intracellular cytoplasmic mislocation.
Ectonucleoside triphosphate diphosphohydrolase 3
Increase of ATPase activity, decrease of ADPase activity.
Increase of activity, especially the ATP hydrolysis.
Loss of ATPase activity, increase of ADPase activity.
Found in a patient with intellectual disability, seizures, mild hypotonia and no speech.
Decreased activity toward linear ubiquitin.
Decreased affinity for linear diubiquitin.
In AIPDS; decreased stability; impaired ability to mediate deubiquitination of linear polyubiquitin chains; increased NF-kappa-B signaling; does not affect ability to interact with RNF31.
In AIPDS; slightly impaired ability to mediate deubiquitination of linear polyubiquitin chains; does not affect ability to interact with RNF31.
Results in strong reduction of kcat while not affecting KM.
Stabilizes H-339 in the active conformation, generating a more reactive enzyme.
Strongly reduced interaction with RNF31.
Cilia- and flagella-associated protein 58
In SPGF49; results in loss of mutant protein; results in axonemal abnormalities.
In SPGF49; unknown pathological significance.
Abolishes sumoylation, abolishes interaction with HDAC1, increases TP53 coactivation and promotes polyubiquitination.
Binds to the tau stem-loop-containing RNA. Inhibits tau exon 10 inclusion and RNA cleavage. Does not inhibit interaction with RBM4.
Probable ATP-dependent RNA helicase DDX5
Transmembrane gamma-carboxyglutamic acid protein 3
Abolishes Monooxygenase activity and impairs ability to control docking and fusion of exocytic carriers.
In MICAL-3NLSMut; abolishes nuclear localization.
Ankyrin repeat domain-containing protein 50
Rare variant found in Diamond-Blackfan anemia patients; unknown pathological significance.
In FHEIG; gain-of-function variant resulting in highly increased basal potassium currents; impaired sensitivity to arachidonic acid.
Increases basal level of channel activity and decreases further activation by pressure, but has little effect on further activation by arachidonic acid.
Strongly increases basal level of channel activity, decreases further activation by pressure and abolishes further activation by arachidonic acid.
von Willebrand factor D and EGF domain-containing protein
Ankyrin repeat domain-containing protein 13D
Does not affect D-fructose or D-glucose transport.
Solute carrier family 2, facilitated glucose transporter member 5
Brain-enriched guanylate kinase-associated protein
Found in prostate cancer samples; unknown pathological significance.
In PC; rare variant associated with disease susceptibility.
Abolishes in vitro enzyme activity; when associated with A-473.
Abolishes in vitro enzyme activity; when associated with A-477.
Decreased enzyme activity. Impairs protein stability.
Decreased protein stability. Decreased enzyme activity.
In MDDGA3; found on the same allele as Q-311; unknown pathological significance.
In MDDGA3; specific activity abolished in the membrane bound form but not the soluble form.
In MDDGA3; specific activity abolished of the membrane bound form but not the soluble form.
In MDDGC3; normal enzyme activity but altered kinetic properties.
In RP76; no effect on protein abundance; reduced acetylglucosaminyltransferase activity.
In RP76; reduced acetylglucosaminyltransferase activity.
Moderately increased enzyme activity. Decreased affinity for N-acetylglucosamine.
Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2
C-Jun-amino-terminal kinase-interacting protein 4
In GPIBD17; decreased expression of GPI-anchored proteins, including FCGR3B/CD16B and CD55, in patient's granulocytes.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit H
Abolishes formation and extrusion of tubulo-vesicular structures and decreases lysosomal exocytosis when overexpressed.
Abolishes interaction with PDCD6 and decreases formation of aberrant endosomes upon overexpression.
Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-15.
Abolishes localization to lysosomes and leads to expression at the cell membrane; when associated with A-577.
Dileucine internalization motif; mediates AP2 complex-dependent internalization
Dileucine motif; mediates targeting to lysosomes
Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with K-144.
Disrupts tetrameric assembly and abolishes lysosomal localization; when associated with S-146.
Does not prevent proteolytic cleavage but changes cleavage pattern.
Fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells.
In ML4; affects channel activity; abolishes Fe(2+) permeability.
In ML4; decreases formation and extrusion of tubulo-vesicular structures when overexpressed; disrupts tetrameric assembly; abolishes lysosomal localization.
In ML4; does not affect channel activity; affects channel inhibition by low pH; impairs Fe(2+) permeability.
In ML4; fails to localize to late endosomes; abolishes Fe(2+) permeability; disrupts tetrameric assembly; abolishes lysosomal localization.
In ML4; mild psychomotor involvement; does not affect channel activity; affects channel inhibition by low pH; still localizes to late endosomes.
In ML4; still localizes to late endosomes; fails to rescue defect of lactosylceramide traffic through the late endocytic pathway in ML4 patient cells; minor effect on formation and extrusion of tubulo-vesicular structures when overexpressed.
Mediates localization to the plasma membrane and strong inwardly rectifying current.
Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-111 and Q-114.
Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-111 and Q-115.
Modulates inhibition by Ca(2+) at different pH levels but does not abolish channel inward rectification; when associated with Q-114 and Q-115.
Modulates ion conduction; when associoated with C-110 and C-112.
Modulates ion conduction; when associoated with C-110 and C-113.
Modulates ion conduction; when associoated with C-112 and C-113.
Processed zona pellucida sperm-binding protein 1
Abolishes expression of A-type isoforms.
Abolishes expression of B-type isoforms.
Abolishes expression of C-type isoforms; when associated with I-86 and I-90.
Abolishes expression of C-type isoforms; when associated with I-86 and I-98.
Abolishes expression of C-type isoforms; when associated with I-90 and I-98.
Abolishes expression of D-type isoforms; when associated with I-316 and I-331.
Abolishes expression of D-type isoforms; when associated with I-316 and I-336.
Abolishes expression of D-type isoforms; when associated with I-331 and I-336.
Abolishes phosphorylation and enhances transcriptional activation.
Abolishes phosphorylation. Does not affect translocation to the nucleus following ligand stimulation. Increases protein half-life and transcriptional repressor activity. Alters repertoire of regulated genes. Increases cell death.
Decrease in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-480; A-494 and A-495.
Decrease in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-492; A-494 and A-495.
Decrease in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-494. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 and A-494.
Decrease in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-495. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 and A-495.
Decreases dimerization and transactivation by dexamethasone; when associated with S-602.
Decreases transactivation by dexamethasone by 95%.
Does not affect the activity of isoform Alpha-C3.
Does not affect translocation to the nucleus following ligand stimulation.
Enhances transactivation activity; does not affect transrepression activity; may increase sensitivity to exogenously administered glucocorticoids; may contribute to central obesity in men and show lack of association with other risk factors for coronary heart disease and diabetes mellitus.
In GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant.
In GCCR; decreased DNA-binding and transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type.
In GCCR; interferes with translocation to the nucleus and thereby strongly reduces transcription activation; is equally impaired in nuclear export; acts as dominant negative mutant.
In GCCR; loss of DNA-binding and of transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type.
In GCCR; loss of dexamethasone-binding, dexamethasone-induced translocation to the nucleus and of transactivation activity.
In GCCR; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding.
In GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant.
In GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding.
In GCCR; unknown pathological significance; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding.
In GCCR; unknown pathological significance; reduces transactivation and transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not impair DNA binding.
In GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding.
In isoform Beta, isoform Beta-B, isoform Beta-2 and isoform GR-A beta.
In isoform GR-A alpha and isoform GR-A beta.
In pseudohermaphroditism; female with hypokalemia due to glucocorticoid resistance; 6-fold reduction in binding affinity compared with the wild-type receptor.
Increases solubility. No effect on transactivation by dexamethasone.
Reduces activation mediated by ligand binding domain; when associated with A-585.
Reduces activation mediated by ligand binding domain; when associated with A-590.
Reduces activity of isoform Alpha-C3 by half.
Reduces expression of target genes IGFBP1 and IRF8.
Reduces transactivation activity; does not affect transrepression activity.
Reduces transactivation by the ADA complex.
Reduces transcription activation activity of isoform Alpha-C3 by half.
Reduces transcription activation activity of isoform Alpha-C3 by half. Suppresses apoptosis-inducing activity of isoform Alpha-C3. Impairs recruitment of selected coregulators onto DNA binding sites.
Slightly reduces sumoylation. Inhibits the stimulatory effect of RWDD3 on its transcriptional activity.
Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-277.
Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-293.
Strongly reduces transactivation by the ADA complex.
Strongly reduces transactivation by the ADA complex; when associated with A-194 and F-225.
Strongly reduces transactivation by the ADA complex; when associated with A-194 and V-224.
Strongly reduces transactivation by the ADA complex; when associated with L-235.
Strongly reduces transactivation by the ADA complex; when associated with V-224 and F-225.
Strongly reduces transactivation by the ADA complex; when associated with V-236.
Variant of uncertain significance; associated in cis with A-321 and S-766 in one individual; doubles transactivation potential.
Variant of uncertain significance; associated in cis with D-72 and A-321 in one individual; doubles transactivation potential.
Variant of uncertain significance; associated in cis with D-72 and S-766 in one individual; doubles transactivation potential.
Abolishes the decapping activity on incomplete m7G cap mRNAs; when associated with A-236.
Abolishes the decapping activity on incomplete m7G cap mRNAs; when associated with A-253.
Impaired subcellular location, leading to localization both in cytoplasm and nucleus.
General transcription factor 3C polypeptide 1
Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase
May act as disease modifier and exacerbate clinical severity in patients with a congenital disorder of glycosylation; slightly decreased function as shown by rescue experiments of defective glycosylation in an alg6-deficient S.cerevisiae strain.
Cyclic nucleotide-gated olfactory channel
Transcription termination factor 3, mitochondrial
Found as heterozygous variant in a patient with Bardet-Biedl syndrome; hypomorphic variant in vitro.
In ACLS; atypical phenotype; unknown pathological significance.
In ACLS; may affect splicing; hypomorphic mutation in vitro.
In BBS; the patient also carries homozygous mutation R-390 in BBS1; may affect splicing; hypomorphic variant in vitro.
In BBS; the patient is a compound heterozygote for a truncating mutation and mutation R-390 in BBS1; hypomorphic variant in vitro.
In BBS; the patient is a compound heterozygote for two frameshift mutations in BBS9; hypomorphic variant in vitro.
In JBTS12; found in a patient with Joubert syndrome that also carries mutations L-358 and T-833 in TMEM67.
Rare variant found in a patient with Bardet-Biedl syndrome also carrying a frameshift mutation in BBS10 and variant P-293 in BBS7.
Amyloid-beta A4 precursor protein-binding family A member 3
Glutamate receptor-interacting protein 2
Amiloride-sensitive sodium channel subunit alpha
In BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents.
In BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents.
In PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents.
Results in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an increased risk for ischemic cerebrovascular events.
Significant decrease of amiloride-sensitive sodium currents.
Significant increase of amiloride-sensitive sodium currents.
Fails to activate interleukin-1 beta production.
Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337.
Impairs DNA binding; when associated with A-160; A-K162; A-163; A-198; A-204. Impairs DNA binding; when associated with A-160; A-162; A-163; A-198; A-204; A-244; A-251; A-309; A-311; A-355 and A-337.
Found in a patient with cohesinopathy; unknown pathological significance.
Abolishes interaction with histone monoubiquitinated H2B without affecting the interaction with H2A.
Abolishes phosphorylation at this position.
Does not affect symoylation; when associated with A-19; A-31; A-52 and A-61.
Does not affect symoylation; when associated with A-9; A-19; A-31 and A-52.
Does not affect symoylation; when associated with A-9; A-19; A-31 and A-61.
Does not affect symoylation; when associated with A-9; A-19; A-52 and A-61.
Does not affect symoylation; when associated with A-9; A-31; A-52 and A-61.
Impairs localization to DNA damages sites; when associated with A-92; S-113 and A-117.
Impairs localization to DNA damages sites; when associated with S-88; S-113 and A-117.
Impairs the selectivity for 'K-63'-linked ubiquitin.
Impairs ubiquitin-binding and localization to DNA damages sites; when associated with S-88; A-92 and A-117.
Impairs ubiquitin-binding and localization to DNA damages sites; when associated with S-88; A-92 and S-113.
Increases the selectivity for 'K-63'-linked ubiquitin.
Not associated with susceptibility to breast cancer.
Slightly impairs the selectivity for 'K-63'-linked ubiquitin.
Strongly reduces ubiquitin binding via UIM 1.
Strongly reduced metal-dependent interaction with integrin; when associated with A-141.
Strongly reduced metal-dependent interaction with integrin; when associated with A-42.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-491; A-497; A-528; A-534 and A-574.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-491; A-497; A-528; A-534 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-491; A-497; A-528; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-491; A-497; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-491; A-528; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-458; A-497; A-528; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-452; A-491; A-497; A-528; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-426; A-458; A-491; A-497; A-528; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-420; A-452; A-458; A-491; A-497; A-528; A-534; A-574 and A-581.
Abolishes the ability to bind promoter of BMP target genes; when associated with A-426; A-452; A-458; A-491; A-497; A-528; A-534; A-574 and A-581.
In NPHP14; found at homozygosity in two siblings with nephronophthisis, cerebellar vermis hypoplasia and situs inversus.
In CRJS; constitutive activation of the smoothened signaling pathway.
In basal cell carcinoma and ameloblastoma samples; somatic mutation; constitutive activation of the smoothened signaling pathway.
In basal cell carcinoma samples; somatic mutation.
Abolishes deubiquitination by USP9X and increases interaction with MTOR. No effect on interaction with SIN1.
Phosphothreonine; by GSK3-alpha and GSK3-beta
Reduced GSK3-mediated phosphorylation, reduced interaction with FBXW7, reduced FBXW7-mediated ubiquitination and increased stability.
Peptidyl-glycine alpha-amidating monooxygenase
EH domain-binding protein 1-like protein 1
60% reduction in phosphatase activity towards PtdIns(3,4,5)P3.
700-fold reduction in phosphatase activity towards PtdIns(3,4,5)P3. Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation.
75% reduction in phosphatase activity towards PtdIns(3,4,5)P3.
75% reduction in phosphatase activity towards PtdIns(3,4,5)P3. Modest reduction in phosphatase activity towards PtdIns(3,4)P2.
85% reduction in phosphatase activity towards PtdIns(3,4,5)P3.
Cytoplasmic; when associated with E-13. Shows less tumor suppressive ability; when associated with E-13.
Does not affect the ability to inhibit AKT/PKB activation.
Does not reduce phosphatase activity towards PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
Does not reduce phosphatase activity towards PtdIns(3,4,5)P3.
Expression is restricted to isoform alpha.
Foun in a patient with macrocephaly, ventriculomegaly, vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia and other limb defects; unknown pathological significance.
In CWS1 and LDD; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In CWS1 and endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
In CWS1 and glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In CWS1; loss of interaction with NOP53; decreased phosphorylation at S-380; decreased stability; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P3.
In CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes.
In CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In CWS1; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
In CWS1; no lipid phosphatase activity but retains protein phosphatase activity; retains ability to inhibit focal adhesion formation.
In CWS1; phosphatase-dead protein with neither lipid nor protein phosphatase activity.
In CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4 but PtdIns(3,4,5)P3 phosphatase activity is similar to wild-type.
In CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4.
In CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
In CWS1; reduced phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes; predominantly nuclear.
In CWS1; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In GLM2; the patient also suffered from benign meningioma; not capable of inducing apoptosis; induced increased cell proliferation; led to high constitutive AKT1 activation which could not be increased further by stimulation with insulin.
In a patient with prostate cancer; reduced phosphatase activity towards PtdIns(3,4,5); shifts its activity from phosphatidylinositol phosphate 3-phosphatase to phosphatidylinositol phosphate 5-phosphatase; disrupts PI3K/ATK signaling; reduced cell migration.
In breast cancer; severely reduced protein phosphatase activity.
In endometrial cancer; loss of protein phosphatase activity.
In endometrial hyperplasia; loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains ability to bind phospholipid membranes.
In endometrial hyperplasia; reduced phosphatase activity towards PtdIns(3,4,5)P3; mildly reduced tumor suppressor activity; reduced ability to inactivate AKT/PKB.
In glioblastoma; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In glioblastoma; reduced tumor suppressor activity; loss of interaction with NOP53; decreased phosphorylation at S-380; decreased stability; loss of phosphatase activity towards Ins(1,3,4,5)P4; reduced ability to inactivate AKT/PKB; retains ability to bind phospholipid membranes.
In glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4.
In glioblastoma; severely reduced protein phosphatase activity; loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
In glioma; loss of protein phosphatase activity.
In glioma; reduced tumor suppressor activity; fails to inactivate AKT/PKB.
In glioma; retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes.
In malignant melanoma; somatic mutation.
In one patient with clinical findings suggesting hamartoma tumor syndrome.
In prostate cancer; no effect on protein phosphatase activity; reduced phosphatase activity towards Ins(1,3,4,5)P3 but retains PtdIns(3,4,5)P3 phosphatase activity.
Loss of DLG1-, MAGI2-, MAGI3- and MAST2-binding. Decrease of protein stability.
Loss of DLG1-, MAGI2-, MAGI3-, MAST1-, MAST2- and MAST3-binding.
Loss of DLG1-binding. No effect on MAGI2- and MAST2-binding.
Loss of phosphatase activity towards Ins(1,3,4,5)P3.
Loss of phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3.
Loss of phosphatase activity towards Ins(1,3,4,5)P4.
Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains ability to bind phospholipid membranes.
Loss of phosphatase activity towards Ins(1,3,4,5)P4; retains the ability to bind phospholipid membranes.
Loss of protein phosphatase activity. Unable to inhibit focal adhesion formation.
No effect on MAGI2-, MAST2- and DLG1-binding.
Nuclear. Cytoplasmic; when associated with E-289. Shows less tumor suppressive ability; when associated with E-289.
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains PtdIns(3,4,5)P3 phosphatase activity.
Reduced phosphatase activity towards Ins(1,3,4,5)P4; retains phosphatase activity towards PtdIns(3,4,5)P3.
Reduced phosphatase activity towards PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(3)P.
Reduces growth suppression activity and promotes anchorage-independent growth. Reduces binding to phospholipid membranes in vitro; phosphatase activity towards PtdIns(3,4,5)P3 is not affected.
Reduces the growth suppression activity and cells show anchorage-independent growth. Reduces binding to phospholipid membranes in vitro. Phosphatase activity towards PtdIns(3,4,5)P3 is not affected.
Retains Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 phosphatase activity; retains ability to bind phospholipid membranes.
Retains phosphatase activity towards Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3; retains the ability to bind phospholipid membranes.
Significantly lower phosphatase activity, reduced protein stability and decreased growth-inhibitory effect.
SUMO interaction motif 1 (SIM); mediates the binding to polysumoylated substrates
SUMO interaction motif 2 (SIM); mediates the binding to polysumoylated substrates
Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-293.
Abolishes MAPK14-mediated phosphorylation. No effect on MAPK7-mediated phosphorylation; when associated with A-300.
Abolishes sumoylation. Enhanced transcriptional activity.
No change in transactivational activation for isoforms with or without the beta domain.
No effect on MAPK14-mediated phosphorylation. Abolishes MAPK7-mediated phosphorylation and reduces transactivation activity.
No effect on sumoylation. No effect on transcriptional activity.
No effect on transcriptional activation.
Probable disease-associated variant found in a patient with infantile onset epileptic encephalopathy and autism spectrum disorder.
Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-252.
Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-239 and R-264.
Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-234; R-252 and R-264.
Reduced acetylation. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-119; R-239; R-252 and R-264.
Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-116; R-234; R-239; R-252 and R-262.
Reduced acetylation. Further reduction in acetylation; when associated with R-119. Complete loss of acetylation, 15% less transactivation activity and slightly reduced DNA binding; when associated with R-119; R-234; R-239; R-252 and R-262.
Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with N-273 and N-275.
Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-273.
Reduced transcriptional activation. Completely abolishes transcriptional activation; when associated with Q-272 and N-275.
CB1 cannabinoid receptor-interacting protein 1
Heterochromatin protein 1-binding protein 3
No effect on the regulation of STING1-mediated innate immune response.
Protein mono-ADP-ribosyltransferase PARP15
Reduces catalytic activity 20-fold. Abolishes activity; when associated with Y-559 and A-560.
Slightly reduces catalytic activity. Abolishes activity; when associated with Y-559 and C-604.
Decreases nuclear localization and ubiquitination of NF-kappa-B subunit RELA.
In ovarian cancer and renal cell carcinoma cell lines.
Increases diffused cytoplasm localization, loss of interaction with ACTB and colocalization with nuclear F-actin, decreases COMMD1 protein stability and ubiquitination of NF-kappa-B subunit RELA and decreases focal adhesion (FA) disassembly and cell migration; when associated with 122-A-A-123.
Increases diffused cytoplasm localization, loss of interaction with ACTB and colocalization with nuclear F-actin, decreases COMMD1 protein stability and ubiquitination of NF-kappa-B subunit RELA and decreases focal adhesion (FA) disassembly and cell migration; when associated with 65-A-A-66.
Increases nuclear and diffused cytoplasm localization, decreases interaction with MAP1A, alters actin cytoskeleton organization and decreases focal adhesion (FA) disassembly and cell migration.
Decreased anion selectivity. Increased permeabilities not only for chloride, but also for sodium and thiocyanate. No effect on transepithelial resistance.
Decreased anion selectivity. No effect on transepithelial resistance.
Decreased transepithelial resistance and anion selectivity.
Decreased transepithelial resistance and anion selectivity. Higher permeability to chloride, sodium and also to larger anions, including pyruvate, nitrate, and thiocyanate.
Decreased transepithelial resistance, no effect on anion selectivity.
Increased transepithelial resistance. Loss of anion selectivity in favor of cation (sodium) selectivity.
Increased transepithelial resistance. No effect on localization to cell-cell junctions.
Loss of anion selectivity. Strongly increased permeabilities not only for chloride, but also for sodium and the larger anions, including pyruvate, nitrate and thiocyanate. No effect on localization to cell-cell junctions.
No effect on channel formation ability. Loss of anion selectivity in favor of cation selectivity. No effect on transepithelial resistance.
No effect on transepithelial resistance, nor on anion selectivity. Elevated permeabilities not only for chloride, but also for sodium and the larger anions, including pyruvate, nitrate and thiocyanate.
No effect on transepithelial resistance, nor on anion selectivity. Increased permeability for thiocyanate.
Reduced channel formation ability. Increased transepithelial resistance. Loss of anion selectivity in favor of cation selectivity.
Strongly reduced channel formation ability. Increased transepithelial resistance. Loss of anion selectivity in favor of cation selectivity.
Complete loss of interaction with PPIA/CYPA.
In LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability.
Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
Decreases in vitro phosphorylation by PKC.
Loss of phosphorylation and interaction with ERBB3 and HUWE1.
No effect on in vitro phosphorylation by PKC.
No effect on phosphorylation and loss of nucleolar localization.
Autophosphorylated but displays limited spermine-induced ATPase activity and lacks spermine-induced dephosphorylation.
In KRS; decreased ATPase activity; no effect on stability; no effect on location.
In KRS; decreased protein stability; increased degradation by proteasome; novel location to endoplasmic reticulum; loss of lysosomal membrane location; impaired autophagosome-lysosome fusion; impaired degradation of protein aggregates.
In KRS; decreased protein stability; loss of autophosphorylation; increased degradation by proteasome; novel location to endoplasmic reticulum; loss of lysosomal membrane location; impaired autophagosome-lysosome fusion; impaired degradation of protein aggregates.
In KRS; found in two affected brothers also carrying C-481 in FBXO7; decreased protein stability; increased degradation by proteasome; novel location to endoplasmic reticulum; loss of ATPase activity; loss of autophosphorylation.
In KRS; no effect on stability; no effect on location; decreased ATPase activity.
In KRS; some patients manifest neuropathologic findings suggestive of neuronal ceroid lipofuscinosis.
In KRS; the mutant protein is retained in the endoplasmic reticulum.
In KRS; unknown pathological significance.
In KRS; unknown pathological significance; associated in cis with Phe-441 in one individual.
In KRS; unknown pathological significance; associated in cis with Thr-1069 in one individual.
In SPG78; no effect on protein stability; loss of autophosphorylation; loss of lysosomal location; loss of ATPase activity.
In a patient with early onset Parkinson disease and KRS; decreased ATPase activity; no effect on autophosphorylation; no effect on stability; no effect on location.
Loss of ATPase function, autophosphorylation and protection against mitochondrial stress.
Reduced spermine-induced ATPase activity and lack of spermine-induced dephosphorylation.
Reduced spermine-induced ATPase activity.
Found in a family with global developmental delay and myopathic hypotonia; unknown pathological significance.
Disrupts interaction with INPP5D/SHIP-1 and PTPN11/SHP-2, no effect on interaction with SH2D1A.
Disrupts interaction with SH2D1A; when associated with A-279.
Disrupts interaction with SH2D1A; when associated with A-325.
Disrupts interaction with SH2D1A; when associated with F-281.
Disrupts interaction with SH2D1A; when associated with F-327.
No effect on interaction with INPP5D/SHIP-1, PTPN11/SHP-2 and SH2D1A.
No effect on interaction with PTPN11/SHP-2 and SH2D1A.
Signaling lymphocytic activation molecule
In ILD2; the mutant protein is retained in the endoplasmic reticulum and is not secreted.
In ILD2; unknown pathological significance; impaired secretion.
In allele 1A(1), allele 1A(3) and allele 1A(4).
Pulmonary surfactant-associated protein A2
In SRTD3; unknown pathological significance.
Probable disease-associated variant found in short rib-polydactyly syndrome 3/6; digenic inheritance; the patient also carries a mutation in NEK1.
39S ribosomal protein L21, mitochondrial
Does not inhibit interaction with APBB1.
Probable disease-associated variant found in patients with familial dilated cardiomyopathy; impairs the formation of SCF complex; reduced ubiquitination of cellular proteins.
Significantly increases nuclear localization.
Completely blocks endoproteolytic processing; when associated with A-226. Completely processed after 6 days of expression, and releases a C-terminal fragment with similar electrophoretic mobility to that obtained by processing wild-type myocilin; when associated with A-226.
Impairs endoproteolytic processing; when associated with A-226. Completely processed after 6 days of expression, and released a C-terminal fragment with similar electrophoretic mobility to that obtained by processing wild-type myocilin; when associated with A-226.
In GLC1A and GLC3A; the GLC3A patient also carries mutation H-368 in CYP1B1 suggesting digenic inheritance.
In GLC1A; forms homomultimeric complexes that migrate at molecular weights larger than their wild-type counterparts; these mutant complexes remain sequestered intracellularly.
In GLC1A; heterozygote specific phenotype.
In GLC1A; incomplete penetrance; inhibits endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum.
In GLC1A; induces stress fiber formation in only 5% of cells.
In GLC1A; inhibits endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum.
In GLC1A; no effect on protein stability.
In GLC1A; severe form; inhibits endoproteolytic processing; produced the highest inhibition of the endoproteolytic processing; mainly accumulates as insoluble aggregates inside the endoplasmic reticulum; inhibits neurite outgrowth.
In GLC1A; unknown pathological significance.
In GLC1A; unknown pathological significance; no significant effect on protein stability.
Loss of higher molecular weight isoform.
Reduced processing. Impairs endoproteolytic processing; when associated with A-229 or A-230. Completely processed after 6 days of expression, and releases a C-terminal fragment with similar electrophoretic mobility to that obtained by processing wild-type myocilin; when associated with A-229 or A-230.
Slightly increases endoproteolytic processing.
Abolishes phosphatase activity. Enhances interaction with NEDD9.
In JMML; also in myelodysplastic syndrome.
In JMML; increases protein tyrosine phosphatase activity against CDC73.
In LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73.
In NS1 and JMML; JMML patient also shows growth retardation and pulmonic stenosis.
In NS1 and LPRD1; does not affect subcellular location; decreases protein tyrosine phosphatase activity against CDC73.
In NS1; also found in myelodysplastic syndrome.
In NS1; also in Noonan patients manifesting juvenile myelomonocytic leukemia.
In NS1; increases MAPK signaling; increased protein tyrosine phosphatase activity.
In NS1; increases MAPK signaling; increases protein tyrosine phosphatase activity; changed substrate selectivity for GAB1.
In NS1; some patients also manifest giant cell lesions of bone and soft tissue.
In NS1; unknown pathological significance.
In acute myeloid leukemia; requires 2 nucleotide substitutions.
Tyrosine-protein phosphatase non-receptor type 11
Mediator of RNA polymerase II transcription subunit 14
Reduced DNA-binding and ability to repress transcription without affecting interaction with SRF. No effect on interaction with DVL2.
50% decrease in scramblase activity in presence of Ca2+, and 40% decrease in scramblase activity in presence of Mg2+.
Abolishes interaction with CNOT7; when associated with Y-1209.
Abolishes interaction with CNOT7; when associated with Y-1257.
CCR4-NOT transcription complex subunit 1
Impairs interaction with CNOT7; when associated with E-1208 and E-1218.
Impairs interaction with CNOT7; when associated with E-1208 and Y-1212.
Impairs interaction with CNOT7; when associated with Y-1212 and E-1218.
In VIBOS; uncertain pathological significance.
2'-5'-oligoadenylate synthase-like protein
Completely abolishes enzyme activity. No change in subcellular location.
Phosphatidylcholine:ceramide cholinephosphotransferase 1
Carnitine O-palmitoyltransferase 1, brain isoform
In SPG73; alters protein conformation; dominant negative mutation.
39S ribosomal protein L34, mitochondrial
In MKS14; unknown pathological significance.
Thioredoxin domain-containing protein 15
Abolishes interaction with CBX3; when associated with A-1003.
Abolishes interaction with CBX3; when associated with A-1005.
Abolishes interaction with CBX5; when associated with E-1003.
Abolishes interaction with CBX5; when associated with E-1005.
In CDLS1; benign variant; no effect on interaction with SCC4.
In CDLS1; no effect on interaction with SCC4.
In CDLS1; strongly inhibits interaction with SCC4.
In CDLS1; unknown pathological significance.
TRAF-type zinc finger domain-containing protein 1
Armadillo repeat-containing X-linked protein 4
Aurora kinase A and ninein-interacting protein
Leukocyte immunoglobulin-like receptor subfamily B member 5
Found in a patient with features of Robinow syndrome; unknown pathological significance.
In OMOD2; also found in a patient with features of Robinow syndrome.
Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members
Probable disease-associated variant found in a patient with features of Robinow syndrome.
Strongly reduced interaction with C.difficile toxin TcdB.
Does not affect localization to centromeres.
Calcium/calmodulin-dependent protein kinase type 1D
U3 small nucleolar ribonucleoprotein protein MPP10
650 fold decrease in antiviral activity.
Selenocysteine-specific elongation factor
Abolishes ATPase activity, dominantly inhibits the TA protein insertion pathway.
Unable to bind DNA; when associated with A-510 and A-657. Still able to bind DNA; when associated with A-657.
Unable to bind DNA; when associated with A-510 and A-688. Still able to bind DNA; when associated with A-688.
Unable to bind DNA; when associated with A-657 and A-688.
In breast pleomorphic lobular sample; somatic mutation.
In cancer cells, may be associated with accelerated disease progression and increased tumor cell motility, possibly due to increased stability of the protease MMP14; leads to phosphorylation at residue Y-390, resulting in prolonged FGFR4 activity; increases interaction with STAT3, resulting in STAT3 phosphorylation and signaling activation..
Associated with Japanese cedar pollinosis.
Gamma-aminobutyric acid receptor subunit rho-2
Calcium/calmodulin-dependent protein kinase II inhibitor 1
Abolished K63-deubiquitinase activity; decreased inhibition of NF-kappa-B; no impact on interaction with TBK1, OPTN and SQSTM.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-441.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-439 and E-444.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-436; E-441 and E-444.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-432; E-439; E-441 and E-444.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-422; E-436; E-439; E-441 and E-444.
Abolishes deubiquitination of TRAF2; when associated with E-418; E-432; E-436; E-439; E-441 and E-444.
Abolishes deubiquitination of TRAF2; when associated with E-422; E-432; E-436; E-439; E-441 and E-444.
In FTDALS8; increased K63-deubiquitinase activity; increased inhibition of NF-kappa-B; no impact on interaction with TBK1, OPTN and SQSTM.
In FTDALS8; unknown pathological significance.
Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-441.
Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-439 and A-444.
Loss of phosphorylation; when associated with A-418; A-422; A-432; A-436; A-441 and A-444.
Reduced phosphorylation; when associated with A-418; A-432 and A-436. Loss of phosphorylation; when associated with A-418; A-432; A-436; A-439; A-441 and A-444.
Reduced phosphorylation; when associated with A-422; A-432 and A-436. Loss of phosphorylation; when associated with A-422; A-432; A-436; A-439; A-441 and A-444.
Slightly reduced phosphorylation; when associated with A-432. Reduced phosphorylation; when associated with A-418; A-422 and A-432. Loss of phosphorylation; when associated with A-418; A-422; A-432; A-439; A-441 and A-444.
Slightly reduced phosphorylation; when associated with A-436. Reduced phosphorylation; when associated with A-418; A-422 and A-436. Loss of phosphorylation; when associated with A-418; A-422; A-436; A-439; A-441 and A-444.
Ubiquitin carboxyl-terminal hydrolase CYLD
Protein phosphatase 1 regulatory subunit 3B
Zinc finger CCHC domain-containing protein 2
Putative uncharacterized protein LINC02908
Acetyl-coenzyme A synthetase 2-like, mitochondrial
Bromo adjacent homology domain-containing 1 protein
Nuclear cap-binding protein subunit 2-like
Homeodomain-interacting protein kinase 1
Loss of kinase activity and impaired MAP3K5-JNK inactivation.
Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-440 and R-1203.
Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-440 and R-556.
Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-317; R-556 and R-1203.
Nuclear subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-25; R-440; R-556 and R-1203.
Reduced sumoylation and cytoplasmic subcellular location. Impaired sumoylation and cytoplasmic subcellular location; when associated with R-317; R-440; R-556 and R-1203.
Glutamate receptor-interacting protein 1
Rho guanine nucleotide exchange factor 4
Transcription initiation factor TFIID subunit 4
Myb/SANT-like DNA-binding domain-containing protein 1
Calcium and integrin-binding family member 4
Pleckstrin homology domain-containing family A member 3
Reduces interaction with IRF4 and transcriptional activation.
In ARVD9; unknown pathological significance.
In ARVD9; unknown pathological significance; decreased interaction with DSP.
In ARVD9; unknown pathological significance; decreased protein stability; decreased interaction with DSP; does not affect subcellular location to the desmosomes.
May be associated with increased susceptibility to arrhythmogenic right ventricular cardiomyopathy.
Reduces phosphorylation of S-82 by MARK3. Reduces interaction with MARK3.
In OORS; defective GPI anchor biosynthesis in homozygous patient cells.
Phosphatidylinositol-glycan biosynthesis class F protein
In allele FMO2*2A; loss of monooxygenase activity.
Probable E3 ubiquitin-protein ligase DTX3
In CHIDG; reduced recombination activity.
V(D)J recombination-activating protein 2
Immunoglobulin-like domain-containing receptor 1
In DFNB42; loss of interaction with MARVELD2; loss of tight junction location.
In DFNB42; no effect on interaction with MARVELD2; loss of tight junction location.
In DFNB42; uncertain pathological significance; no effect on interaction with MARVELD2; no effect on tight junction location.
Abolishes interaction with PRKAR2B and impairs TNFRSF1A release.
Brefeldin A-inhibited guanine nucleotide-exchange protein 2
Disturbs membrane organization at the TGN, impairs association of the AP-1 complex and GGA1 with the TGN membranes.
In PVNH2; unknown pathological significance.
Lymphocyte antigen 6 complex locus protein G6c
In FPVEPD; may affect microtubules stability.
Coiled-coil domain-containing protein 38
In RP18; reduces phosphorylation; impairs binding to PRPF4; impairs self-association; affects interaction with the U4/U5/U6 tri-snRNP complex; does not affect global pre-mRNA splicing.
U4/U6 small nuclear ribonucleoprotein Prp3
Endogenous retrovirus group V member 1 Env polyprotein
DNA repair and recombination protein RAD54-like
Defect in homologous recombination (HR).
In a breast cancer sample; invasive ductal.
Promotes homologous recombination (HR), but causes RAD51 removal from chromatin.
Unable to rescue the MMS-sensitive phenotype of S cerevisiae rad54delta cells.
Defective in regulation of transcriptional elongation.
Enhances interactions with CDK9 and RNA polymerase II and enhances transcriptional elongation; when associated with A-681 and A-698.
Enhances interactions with CDK9 and RNA polymerase II and enhances transcriptional elongation; when associated with A-696 and A-698.
Enhances transcriptional elongation. Enhances interactions with CDK9 and RNA polymerase II and enhances transcriptional elongation; when associated with A-681 and A-696.
Increases promoter association and enhances transcriptional elongation; when associated with K-681 and K-696.
Increases promoter association and enhances transcriptional elongation; when associated with K-681 and K-698.
Increases promoter association and enhances transcriptional elongation; when associated with K-696 and K-698.
Omega-N-methylarginine; by PRMT1 and PRMT5; alternate
Loss of function in inducing TLR2 degradation.
In LCA5; unknown pathological significance.
ADP-ribosylation factor-binding protein GGA1
Abolishes interaction with ARF1 and RABEP1.
Abolishes interaction with ARF1, UBC and TSG101.
Abolishes interaction with IGF2R. No effect on the interaction with SORL1.
Abolishes interaction with RABEP1 and UBC.
Abolishes interaction with RABEP1, UBC and TSG101.
Increased interaction with IGF2R. Reduced phosphorylation. No effect on the interaction with SORL1.
Carcinoembryonic antigen-related cell adhesion molecule 3
Loss of phosphorylation and 30% reduction in bacterial uptake. More than 60% reduction in bacterial uptake and loss of RAC1 stimulation; when associated with F-230.
Loss of phosphorylation and 30% reduction in bacterial uptake. More than 60% reduction in bacterial uptake and loss of RAC1 stimulation; when associated with F-241.
In XLID98; de novo dominant mutation found in females; disease phenotype includes epilepsy as a feature.
In CONPM; loss of catalytic activity in patient fibroblasts.
In CONPM; unknown pathological significance.
V-type proton ATPase 16 kDa proteolipid subunit c
Abolished transmembrane transport of dipeptides.
Does not affect transmembrane transport of dipeptides.
Nearly abolished transmembrane transport of dipeptides.
Reduced transmembrane transport of dipeptides.
WAP four-disulfide core domain protein 6
Associated with low serum mannose-binding protein (MBP) concentrations and recurrent infections.
Associated with low serum mannose-binding protein (MBP) concentrations; associated with protection against tuberculosis caused by Mycobacterium africanum.
In 0.05% of European and African populations.
Loss of aci-reductone dioxygenase activity.
Coiled-coil domain-containing protein 40
Significant loss of interaction with IL1RL1.
Transmembrane emp24 domain-containing protein 1
In JBTS23; unknown pathological significance.
In CSS9; decreases transcriptional activity.
In isoform 11, isoform 14, isoform 15, isoform 16, isoform 17, isoform 18, isoform 21 and isoform 24.
In isoform 12, isoform 13 and isoform 18.
In isoform 19, isoform 20 and isoform 21.
In isoform 22, isoform 23 and isoform 24.
In isoform 3, isoform 5, isoform 7, isoform 8, isoform 10, isoform 13, isoform 20 and isoform 23.
In isoform 9, isoform 10 and isoform 17.
Marked decrease in phosphorylation by MAPK8 or MAPK9. Complete loss of phosphorylation by MAPK8 or MAPK9, but no effect on MAPK8/9-binding; when associated with A-213. Decreased transcriptional activity; when associated with A-213.
Marked decrease in phosphorylation by MAPK8 or MAPK9. Complete loss of phosphorylation by MAPK8 or MAPK9, but no effect on MAPK8/9-binding; when associated with A-217. Decreased transcriptional activity; when associated with A-217.
Nuclear factor of activated T-cells, cytoplasmic 4
Promotes nuclear localization and increases transcriptional activity; when associated with A-168.
Promotes nuclear localization and increases transcriptional activity; when associated with A-170.
Histone-lysine N-methyltransferase SETD7
Induces a reduction in methyltransferase activity toward TAF10 but an increased methyltransferase activity for H3 and p53/TP53.
Significantly reduces the catalytic activity.
Significantly reduces the monomethyltransferase activity but increases the dimethyltransferase activity.
In DEE57; decreased protein abundance; loss of chloride-activated potassium channel activity; loss of potassium selectivity.
90% reduction in TGF-beta receptor binding.
Diminishes interaction with SMURF2 and reduces inhibition of TGF-beta signaling.
Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-64.
Loss of acetylation, and of SMURF1-dependent degradation; when associated with A-70.
Mothers against decapentaplegic homolog 7
Loss of localization to the Golgi. No effect on the ceramidase activity.
Leucine-rich repeat-containing protein 24
Loss of mitogenic activity of CUB domain in coronary artery smooth muscle cells.
Platelet-derived growth factor C, latent form
Platelet-derived growth factor C, receptor-binding form
Pyridoxal-dependent decarboxylase domain-containing protein 1
Abolishes phosphorylation by CDK2, leading to lower deubiquitinase activity.
Impaired interaction with FZR1/CDH1 and subsequent ubiquitination.
Ubiquitin carboxyl-terminal hydrolase 37
Reduced interaction with the DCX(AMBRA1) complex, and subsequent ubiquitination and degradation by the proteasome.
Reduced interaction with the DCX(AMBRA1) complex, and subsequent ubiquitination and degradation by the proteasome. Abolished ubiquitination and subsequent degradation following DNA damage.
Reduced ubiquitination and subsequent degradation by the proteasome.
Probable disease-associated variant found in patients with pathologic myopia; may decrease mitochondrial complex I activity; decreases the production of ATP; decreases reactive oxygen species production.
Protein arginine methyltransferase NDUFAF7, mitochondrial
2-fold reduction in binding affinity for STN1.
2.5-fold reduction in binding affinity for STN1.
Abolishes homodimerization. No effect on ATPase activity. Loss of HUSH-dependent gene silencing.
Abolishes phosphorylation by PAK1. Not recruited on damaged chromatin. Loss of ATPase activity. Prevents chromatin remodeling. Upon irradiation, increases levels of damaged DNA.
In CMT2Z and DIGFAN; decreased ATPase activity; ATP-independent homodimerization; increases HUSH-dependent gene silencing.
In CMT2Z; increases HUSH-dependent gene silencing.
In CMT2Z; slightly decreased ATPase activity; increases HUSH-dependent gene silencing.
In CMT2Z; unknown pathological significance.
In DIGFAN; increases HUSH-dependent gene silencing.
Increases HUSH-dependent gene silencing.
Loss of ATP-binding and ATPase activity. Does not homodimerizes. Seems to abolish chromatin compaction.
Loss of ATP-binding and ATPase activity. Loss of binding to ATP and ATPase activity; when associated with A-69. Prevents chromatin remodeling.
Loss of HUSH-dependent gene silencing. Decreases dsDNA-binding affinity; when associated with E-326 and E-329.
Loss of HUSH-dependent gene silencing. Decreases dsDNA-binding affinity; when associated with E-326 and E-333.
Loss of HUSH-dependent gene silencing. Decreases dsDNA-binding affinity; when associated with E-329 and E-333.
No effect on HUSH-dependent gene silencing.
No effect on binding to ATP and ATPase activity; when associated with A-68.
Probable disease-associated variant found in a child with spinal atrophy-phenotype, cerebellar atrophy and diaphragmatic paralysis; also found in a second child with early onset cerebellar ataxia, axonal polyneuropathy and nocturanl hypoventilation; increased ATPase activity; increased rate of dimer assembly and disassembly; decreased HUSH-dependent gene silencing.
2-fold increased enzyme activity with a lower specificity for glycine and higher for succinyl-CoA.
5-aminolevulinate synthase, erythroid-specific, mitochondrial
In SIDBA1; 12% to 25% activity of wild-type.
In SIDBA1; 15% to 35% activity of wild-type.
In SIDBA1; associated in cis with L-520 in a patient.
In SIDBA1; likely benign variant; associated in cis with H-560 in a patient.
In SIDBA1; significantly increased thermosensitivity.
In SIDBA1; significantly reduced activity.
Rare variant found in a congenital erythropoietic porphyria patient that also carries UROS mutations R-73 and Q-248; increased enzyme activity.
HLA class II histocompatibility antigen, DQ alpha 1 chain
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04 and allele DQA1*01:05.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05 and allele DQA1*01:07.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:06 and allele DQA1*01:07.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:06 and allele DQA1*01:07; requires 2 nucleotide substitutions.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:06, allele DQA1*01:07, allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02 and allele DQA1*03:03.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:06, allele DQA1*01:07, allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02, allele DQA1*03:03, allele DQA1*04:01, allele DQA1*04:02, allele DQA1*04:04, allele DQA1*06:01 and allele DQA1*06:02.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:07, allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02, allele DQA1*03:03, allele DQA1*04:01, allele DQA1*04:02, allele DQA1*04:04, allele DQA1*06:01 and allele DQA1*06:02.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*04:01 and allele DQA1*06:01.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05,allele DQA1*01:06 and allele DQA1*01:07.
In allele DQA1*01:01, allele DQA1*01:02, allele DQA1*01:04, allele DQA1*01:05 and allele DQA1*01:07.
In allele DQA1*01:01, allele DQA1*01:02,allele DQA1*01:03, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:06 and allele DQA1*01:07.
In allele DQA1*01:01, allele DQA1*01:04, allele DQA1*01:05, allele DQA1*01:07, allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02 and allele DQA1*03:03.
In allele DQA1*01:04 and allele DQA1*01:05.
In allele DQA1*02:01, allele DQA1*01:03, allele DQA1*06:01 and allele DQA1*06:02.
In allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02 and allele DQA1*03:03.
In allele DQA1*02:01, allele DQA1*03:01, allele DQA1*03:02, allele DQA1*03:03, allele DQA1*04:01, allele DQA1*04:02, allele DQA1*04:04, allele DQA1*06:01 and allele DQA1*06:02.
In allele DQA1*02:01; requires 2 nucleotide substitutions.
In allele DQA1*03:01, allele DQA1*03:02 and allele DQA1*03:03.
In allele DQA1*03:01, allele DQA1*03:02 and allele DQA1*03:03; requires 2 nucleotide substitutions.
In allele DQA1*03:02 and allele DQA1*03:03.
In allele DQA1*04:01, allele DQA1*04:02, allele DQA1*04:04, allele DQA1*06:01 and allele DQA1*06:02; requires 2 nucleotide substitutions.
In allele DQA1*05:03, allele DQA1*05:06 and allele DQA1*05:07.
In allele DQA1*05:05, allele DQA1*05:08 and allele DQA1*05:09.
Decreased vitamin K epoxide reductase activity.
Decreases enzyme activity by about 80%. Decreases inhibition by warfarin.
Decreases enzyme activity moderately. Decreases inhibition by warfarin.
Decreases enzyme activity moderately. Strongly decreases inhibition by warfarin.
In VKCFD2; strongly reduced enzyme activity.
No effect on enzyme activity. Decreases inhibition by warfarin.
No effect on enzyme activity. Strongly decreases inhibition by warfarin.
Reduces enzyme activity by about 80%. Decreases inhibition by warfarin.
Vitamin K epoxide reductase complex subunit 1
vitamin-K-epoxide reductase (warfarin-sensitive)
Abolishes calcium-dependent association with membranes; when associated with A-39 and A-44.
Abolishes calcium-dependent association with membranes; when associated with A-39 and A-85.
Abolishes calcium-dependent association with membranes; when associated with A-44 and A-85.
Changes the stereoselectivity of the oxygenation reaction. Completely changes the stereoselectivity of the oxygenation reaction to produce (8S)-HPETE instead of (15S)-HPETE; when associated with Y-602.
Does not affect arachidonate 15-lipoxygenase activity; destabilizes the enzyme structure.
Does not affect arachidonate 15-lipoxygenase activity; does not impact enzyme structure.
No effect on the stereoselectivity of the oxygenation reaction. Completely changes the stereoselectivity of the oxygenation reaction to produce (8S)-HPETE instead of (15S)-HPETE; when associated with H-603.
Polyunsaturated fatty acid lipoxygenase ALOX15B
5'-nucleotidase domain-containing protein 3
In CMS8; decreased AGRN-induced clustering of AChR by >100-fold and decreased phosphorylation of the MUSK receptor and AChR beta subunit by about 10-fold. Increased binding to alpha-dystroglycan.
In CMS8; results in decreased AChR clustering.
In CMS8; results in disruption of the neuromuscular junction architecture; does not affect phosphorylation of MUSK; does not affect AChR clustering.
Found in a patient with primary pulmonary hypertension; unknown pathological significance; affects SMAD-mediated signaling.
Mothers against decapentaplegic homolog 1
Phosphothreonine; by MINK1, TNIK and MAP4K4
Leucine-rich repeat-containing protein 3B
Abolishes interaction with ATF7IP and subsequent transcription repression activity.
Disrupts tertiary structure and abolishes DNA binding.
In isoform 2, isoform 4, isoform 6, isoform 8 and isoform 11.
Strongly reduces binding to methylated DNA.
Ribosome biogenesis regulatory protein homolog
TPR and ankyrin repeat-containing protein 1
Trifunctional enzyme subunit beta, mitochondrial
In RP13; no effect on interaction with SNRNP200 and EFTUD2.
In RP13; reduces interaction with EFTUD2, but not with SNRNP200.
In RP13; reduces interaction with SNRNP200 and EFTUD2.
RNA polymerase-associated protein RTF1 homolog
Potassium voltage-gated channel subfamily H member 4
In OPA12 and SPAX5; decreased proteolytic function.
In OPA12; decreased proteolytic function resulting in impaired autocatalytic processing and impaired proteolytic maturation of SPG7; does not affect the interaction with SPG7.
In OPA12; decreased proteolytic function.
In OPA12; loss-of-function variant resulting in aberrant OPA1 processing and mitochondrial fragmentation.
In OPA12; unknown pathological significance.
In OPA12; unknown pathological significance; decreased proteolytic function.
In SCA28; impaired function shown in a yeast complementation assay.
In SCA28; unknown pathological significance.
In SPAX5; hypomorphic mutation; results in impaired oligomerization with itself and SPG7; retains ATPase and proteolytic activities.
In SPAX5; impaired function shown in a yeast complementation assay.
In SPAX5; unknown pathological significance.
Loss of autocatalytic processing. Impaired proteolytic maturation of SPG7.
Abolishes interaction with DDX6; when associated with A-300.
Abolishes interaction with DDX6; when associated with A-306.
In PARK11; unknown pathological significance.
Probable disease-associated variant found in a consanguineous family with intellectual disability.
In CPVT3; unknown pathological significance.
In ECYT2, pheochromocytoma and VHLD; type IIA.
In RCC; with paraneoplastic erythrocytosis; inhibits binding to HIF1AN.
In VHLD; type I-II; abolishes release from chaperonin complex and the interaction with Elongin BC complex.
In VHLD; type I; No effect on interaction with HIF1A nor on HIF1A degradation.
In VHLD; type I; requires 2 nucleotide substitutions.
In pheochromocytoma and VHLD; type II; common mutation.
In pheochromocytoma; likely benign variant.
In pheochromocytoma; requires 2 nucleotide substitutions.
No interaction with HIF1A. No HIF1A degradation.
von Hippel-Lindau disease tumor suppressor
In PBD11B; neonatal adrenoleukodystrophy.
Abolishes enzyme activity with UDP-galactose.
Uridine diphosphate glucose pyrophosphatase NUDT22
Probable ATP-dependent RNA helicase DDX60
Ciliogenesis-associated TTC17-interacting protein
In SPGF54; reduces the protein stability. Increases the kinetics of actin polymerisation.
Regulation of nuclear pre-mRNA domain-containing protein 2
Abolished ability to prevent calcium overload.
Mitochondrial sodium/calcium exchanger protein
Phosphomimetic mutant; prevents calcium overload.
Potassium voltage-gated channel subfamily D member 1
Complex I intermediate-associated protein 30, mitochondrial
In MC1DN11; due to a nucleotide substitution located in the splice site consensus sequence at the end of exon 3; patient cells contain normally spliced transcripts corresponding to protein variant R-253 but also transcripts lacking the final 6 base pairs of exon 3 and corresponding to protein variant 252-VK-253 del.
In MC1DN11; due to a nucleotide substitution located in the splice site consensus sequence at the end of exon 3; patient cells contain transcripts lacking the final 6 base pairs of exon 3 but also contain normally spliced transcripts corresponding to protein variant R-253.
Abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when associated with A-113; A-167 and A-197. Reduces phosphatidylinositol 4,5-bisphosphate binding and does not change subcellular localization; when associated with A-197.
Abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when associated with A-113; A-167 and A-244. Reduces phosphatidylinositol 4,5-bisphosphate binding and does not change subcellular localization; when associated with A-244.
Abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when associated with A-113; A-197 and A-244. Reduces phosphatidylinositol 4,5-bisphosphate binding and does not change subcellular localization; when associated with A-113.
Abolishes phosphatidylinositol 4,5-bisphosphate binding and targeting to plasma membrane, speckles and nucleoli; when associated with A-167; A-197 and A-244. Reduces phosphatidylinositol 4,5-bisphosphate binding and does not change subcellular localization; when associated with A-167.
Loss of kinase activity and autophosphorylation.
In allele MICB*001, allele MICB*002, allele MICB*003, allele MICB*005, allele MICB*006, allele MICB*007, allele MICB*008, allele MICB*010, allele MICB*011, allele MICB*012, allele MICB*013, allele MICB*014, allele MICB*015, allele MICB*016, allele MICB*018, allele MICB*019 and allele MICB*022.
In allele MICB*001, allele MICB*002, allele MICB*005, allele MICB*006, allele MICB*007, allele MICB*008, allele MICB*012, allele MICB*013, allele MICB*014, allele MICB*015, allele MICB*016, allele MICB*018, allele MICB*019, allele MICB*020 and allele MICB*022.
In allele MICB*001, allele MICB*016, allele MICB*018, allele MICB*019, allele MICB*020 and allele MICB*022.
In allele MICB*002, allele MICB*007, allele MICB*008, allele MICB*014, allele MICB*015, allele MICB*016, allele MICB*019 and allele MICB*022.
In allele MICB*002, allele MICB*007, allele MICB*008, allele MICB*014, allele MICB*015, allele MICB*018, allele MICB*020 and allele MICB*022.
In allele MICB*013, allele MICB*014, allele MICB*015 and allele MICB*016.
MHC class I polypeptide-related sequence B
Abolishes function, but retains ability to interact with SMAD3; when associated with A-88.
Abolishes function, but retains ability to interact with SMAD3; when associated with A-92.
Slightly decreased phosphodiesterase activity.
Strongly decreased phosphodiesterase activity.
Strongly reduced phosphodiesterase activity.
Abolished ability to regulate RNA metabolism.
Abolished helicase activity and ability to regulate RNA metabolism.
Abolishes interaction with EDC3; when associated with A-320; A-323 and A-327.
Abolishes interaction with EDC3; when associated with A-320; A-323 and A-331.
Abolishes interaction with EDC3; when associated with A-320; A-327 and A-331.
Abolishes interaction with EDC3; when associated with A-323; A-327 and A-331.
In CL-AA; abolishes interaction with PATL1 and reduces interaction with GIGYF1 and GIGYF2, but has no affect on interaction with EDC3, EIF4ENIF1 and LSM14A; when associated with A-324. In 4xmut; abolishes interaction with EDC3; when associated with A-324, A-349 and A-353.
In CL-AA; abolishes interaction with PATL1 and reduces interaction with GIGYF1 and GIGYF2, but has no affect on interaction with EDC3, EIF4ENIF1 and LSM14A; when associated with A-328. In 4xmut; abolishes interaction with EDC3; when associated with A-328, A-349 and A-353.
In IDDILF; decreased P-body assembly; decreased interaction with LSM14A; decreased interaction with LSM14B; decreased interaction with EIF4ENIF1/4E-T.
In IDDILF; decreased P-body assembly; decreased interaction with LSM14A; decreased interaction with LSM14B; decreased interaction with EIF4ENIF1/4E-T; decreased interaction with PATL1.
In LK-AA; abolishes interaction with PATL1 and reduces interaction with GIGYF1, GIGYF2, EDC3, EIF4ENIF1 and LSM14A; when associated with A-349. In 4xmut; abolishes interaction with EDC3; when associated with A-324; A-328 and A-349.
In LK-AA; abolishes interaction with PATL1 and reduces interaction with GIGYF1, GIGYF2, EDC3, EIF4ENIF1 and LSM14A; when associated with A-353. In 4xmut; abolishes interaction with EDC3; when associated with A-324, A-328 and A-353.
Probable ATP-dependent RNA helicase DDX6
Cilia- and flagella-associated protein 74
Does not affect phosphorylation by AMPK.
Reduces phosphorylation by AMPK. Does not affect DNA binding. Does not repress transcription of PCK1.
Rare variant found in a Diamond-Blackfan anemia patient; unknown pathological significance.
Nuclear pore complex-interacting protein family member A5
1.5 kDa decrease of the apparent molecular mass of pro-PCSK9 and PCSK9 and no effect on processing and secretion.
Associated with lower plasma levels of low-density lipoprotein cholesterol.
Associated with lower plasma levels of low-density lipoprotein cholesterol; more extensive cleavage by furin and PCSK5.
Associated with lower plasma levels of low-density lipoprotein cholesterol; reduced phosphorylation at Ser-47.
Associated with reduced phosphorylation at Ser-47.
Does not affect multimerization or zymogen processing.
Found in a patient associated with autosomal dominant hypercholesterolemia; unknown pathological significance.
Found in patients with familial hypercholesterolemia carrying a homozygous LDLR mutation; acts as a disease modifier resulting in a mild phenotype.
In FHCL3; complete loss of cleavage by furin and PCSK5; reduces glycosylation levels; no effect on protein sulfation and phosphorylation; no effect on protein sulfation but inhibits phosphorylation when associated with Y-374; highly reduces LDL uptake when associated with Y-374.
In FHCL3; partial loss of cleavage by furin and PCSK5.
In FHCL3; partial loss of cleavage by furin and PCSK5; no effect on protein sulfation but inhibits phosphorylation when associated with S-218; highly increases LDL uptake when associated with S-218.
Proprotein convertase subtilisin/kexin type 9
Remains in the endoplasmic reticulum and is not secreted.
This variant seems to have a modifier effect on LDLR mutation and familial hypercholesterolemia.
Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with R-409.
Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response; when associated with R-447.
Abolishes interaction with NEDD4 and NEDD4L.
Sperm protein associated with the nucleus on the X chromosome N4
In MRFACD; unknown pathological significance.
In a patient with dextro-looped transposition of the great arteries; unknown pathological significance.
Mediator of RNA polymerase II transcription subunit 13-like
Inactive ubiquitin carboxyl-terminal hydrolase 17-like protein 7
In SEMDK; decreased protein expression; decreased kinase activity; no effect on the interaction with DEPTOR, MLST8/GbetaL, RICTOR and RPTOR.
Loss of interaction with 14-3-3 proteins in response to cAMP signaling; inhibits cAMP signaling.
No effect on interaction with 14-3-3 proteins, nor on cAMP signaling.
Abolished GTPase activation (GAP) activity.
Does not assemble into a stable folliculin complex (LFC), preventing localization to the lysosomal membrane upon amino acid starvation.
Found in a colorectal cell line; impaired protein stability.
Impaired ability to regulate autophagy; when associated with A-406 and A-537.
Impaired ability to regulate autophagy; when associated with A-406 and A-542.
Impaired ability to regulate autophagy; when associated with A-537 and A-542.
In BHD; does not impair protein stability, growth suppression activity or intracellular localization of folliculin.
In PSP and BHD; impaired protein stability.
In a primary clear-cell renal cell carcinoma; somatic mutation.
In a primary colorectal cancer; somatic mutation.
In a sporadic colorectal carcinoma; somatic mutation.
Cell cycle and apoptosis regulator protein 2
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3); alternate
Significantly increases association with SIRT1 and induces p53 acetylation and apoptosis. Increases sumoylation and the interaction of the sumoylated form with SIRT1. Promotes CCAR2-PSIA3 interaction. Decreases CCAR2-SENP1 interaction.
Significantly reduces association with SIRT1. Decreases sumoylation and the interaction of the sumoylated form with SIRT1. Inhibits CCAR2-PSIA3 interaction. Increases CCAR2-SENP1 interaction. Down-regulation of the signals related with the epithelial-mesenchymal transition of gastric cancer cells.
Phosphoinositide 3-kinase regulatory subunit 5
Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities.
DNA-(apurinic or apyrimidinic site) endonuclease 2
Identified in a patient with mtDNA maintenance disorders.
Reduces 3'-5' exonuclease activity in presence of PCNA. Does not abolish the 3'-5' exonuclease activity. Does only partially redistributes together with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents.
Abolishes phosphorylation by PLK2 and procentriole formation; when associated with A-589.
Abolishes phosphorylation by PLK2 and procentriole formation; when associated with A-595.
Decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on association with microtubule lattice; when associated with A-375.
Decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on association with microtubule lattice; when associated with A-385.
Decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on association with microtubule lattice; when associated with E-377.
Decreases interaction with alpha/beta-tubulin; disrupts association with microtubule distal tip; no effect on association with microtubule lattice; when associated with E-378.
Decreases interaction with alpha/beta-tubulin; when associated with A-338 and A-339.
Decreases interaction with alpha/beta-tubulin; when associated with A-338 and A-341.
Decreases interaction with alpha/beta-tubulin; when associated with A-339 and A-341.
In MCPH6; reduced interaction with STIL.
Slightly decreases interaction with alpha/beta-tubulin; causes overly long daughter centrioles and enhances ciliary length; when associated with A-343.
Slightly decreases interaction with alpha/beta-tubulin; causes overly long daughter centrioles and enhances ciliary length; when associated with A-344.
Strongly decreases interaction with alpha/beta-tubulin; causes shorter centrioles and doublet microtubules in cilia.
Protein farnesyltransferase subunit beta
Removes the steric hindrance that normally precludes geranylgeranyl diphosphate binding. Reduces farnesyltransferase activity and confers geranylgeranyltransferase activity.
Found in a patient with autism and Parkinson's disease; unknown pathological significance.
Disrupts oligomerization. Loss of antimicrobial activity.
Impacts oligomerization. Loss of antimicrobial activity.
Loss of antimicrobial activity against M.luteus.
No impact on antimicrobial activity against M.luteus.
Reduced antimicrobial activity against M.luteus.
Slightly increased MIC against E.coli K12 (MIC=15 compared to MIC=5).
Slightly increased MIC against E.coli K12 (MIC=25 compared to MIC=5).
Decreases resistance to vincristine, VP-16 and doxorubicin.
Impairs estradiol glucuronide transport.
Impairs estradiol glucuronide transport; loss of resistance to alkaloid vincristine, cationic anthracyclines, epipodophyllotoxin VP-16, but not potassium antimony tartrate; partial loss of resistance to sodium arsenite.
Impairs leukotriene C4 and estradiol glucuronide transport.
Impairs protein maturation and leukotriene C4 transport.
In DFNA77; changes protein subcellular localization expressed in both membrane and cytoplasm; produces unstable mRNA.
In DFNA77; unknown pathological significance.
In isoform 2, isoform 5, isoform 6 and isoform 8.
In isoform 3, isoform 5, isoform 7 and isoform 8.
In isoform 4, isoform 6, isoform 7 and isoform 8.
Increases estradiol glucuronide transport.
Increases resistance to vincristine and decreases resistance to VP-16.
Multidrug resistance-associated protein 1
No effect on leukotriene C4 and estradiol glucuronide transport.
No effect on protein maturation and leukotriene C4 transport.
Only partially affects protein maturation; impairs leukotriene C4 transport.
Reduced transport of leukotriene C4 and of glutathione.
Reduced transport of leukotriene C4, estradiol glucuronide and of glutathione.
Slightly impairs leukotriene C4 and estradiol glucuronide transport.
Strongly reduced transport of leukotriene C4, estradiol glucuronide and of glutathione.
Abolishes S-315 phosphorylation by CDK2/cyclin A.
Abolishes SUMO1 conjugation, in vitro and in vivo.
Abolishes dimethylation by EHMT1 and EHMT2.
Abolishes phosphorylation by DYRK2 and HIPK2 and acetylation of K-382 by CREBBP.
Abolishes phosphorylation site. Abolishes increase in protein levels after DNA damage.
Constitutively increased TP53 protein levels.
In LFS; germline mutation and in a sporadic cancer; somatic mutation.
In LFS; germline mutation and in sporadic cancers; somatic mutation.
In LFS; germline mutation and in sporadic cancers; somatic mutation; abolishes sequence-specific DNA binding; does not induce SNAI1 degradation.
In LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation.
In LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation; reduces interaction with ZNF385A; loss of susceptibility to calpain.
In LFS; germline mutation and in sporadic cancers; somatic mutation; no effect on susceptibility to calpain.
In a brain tumor with no family history; germline mutation and in sporadic cancers; somatic mutation.
In a breast cancer with no family history; germline mutation and in sporadic cancers; somatic mutation.
In a familial cancer not matching LFS; germline mutation and in a sporadic cancer; somatic mutation.
In a familial cancer not matching LFS; germline mutation and in sporadic cancers; somatic mutation.
In a familial cancer not matching LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation.
In a familial cancer not matching LFS; germline mutation and in sporadic cancers; somatic mutation; no effect on interaction with CCAR2.
In a familial cancer not matching LFS; germline mutation.
In a kidney cancer with no family history; germline mutation and in a sporadic cancer; somatic mutation.
In a sporadic cancer; somatic mutation; abolishes strongly phosphorylation.
In a sporadic cancer; somatic mutation; reduces interaction with ZNF385A.
In a sporadic cancer; somatic mutation; requires 2 nucleotide substitutions.
In an adrenocortical carcinoma with no family history; germline mutation and in sporadic cancers; somatic mutation.
In an osteosarcoma with no family history; germline mutation and in sporadic cancers; somatic mutation.
In familial cancer not matching LFS; germline mutation and in a sporadic cancer; somatic mutation.
In sporadic cancers; somatic mutation; decreased E6-mediated binding to E6-AP.
In sporadic cancers; somatic mutation; does not induce SNAI1 degradation.
In sporadic cancers; somatic mutation; loss of nuclear localization.
In sporadic cancers; somatic mutation; no effect on susceptibility to calpain.
In sporadic cancers; somatic mutation; requires 2 nucleotide substitutions.
In sporadic cancers; somatic mutation; strong DNA binding ability at 32.5 degrees Celsius; strong reduction of transcriptional activity at 37.5 degrees Celsius; severely represses interaction with ZNF385A.
Induces a decrease in methylation by SMYD2.
Induces a decrease in protein stabilization.
Inhibits slightly its transcriptional activity.
Inhibits strongly its transcriptional activity.
Loss of interaction with MDM2, leading to constitutively increased TP53 protein levels.
Loss of interaction with PPP2R5C, PPP2CA AND PPP2R1A.
Loss of nuclear localization; when associated with A-319 and A-320.
Loss of nuclear localization; when associated with A-319 and A-321.
Loss of nuclear localization; when associated with A-320 and A-321.
Mimics acetylation, leading to increased stability.
N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate
No effect on interaction with MDM2 and increase in protein levels after DNA damage.
Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG
Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM
Reduced methylation by PRMT5. Reduced nuclear localization. Decreased binding to promoters of target genes. Reduced transcriptional activity. Decrease in cell cycle arrest.
Ras-related protein Rab-34, isoform NARR
In MCAHS3; flow cytometric analysis of patient granulocytes and monocytes show decreased amounts of GPI-anchored proteins CD16B and CD59 compared to controls.
Abolishes inhibition by zinc allowing zinc ion influx.
In a patient with night blindness started in the third decade; associated in cis with G-1438.
In a patient with night blindness started in the third decade; associated in cis with T-962.
Reduces inhibition by zinc allowing zinc ion influx.
Transient receptor potential cation channel subfamily M member 1
Affecting excitation/contraction coupling in muscle fibers; the sensitivity of CACNA1S voltage sensor is shifted to higher depolarizing voltages in cells carrying this variant.
Junctional sarcoplasmic reticulum protein 1
Abolishes autophosphorylation activity; enhances association with pre-40S ribosomal subunits; inhibits processing of 18S-E pre-rRNA to the mature 18S rRNA.
In HH15; 15 to 30% reduction in enzymatic activity compared to wild-type.
In HH15; approximately 30% reduction in enzymatic activity compared to wild-type when heparan sulfate is the acceptor substrate.
In HH15; with anosmia; 30 to 70% reduction in enzymatic activity compared to wild-type.
In HH15; with anosmia; results in Kallmann syndrome in the presence of FGFR1 mutation Gln-250; approximately 50% reduction in enzymatic activity compared to wild-type.
In HH15; with or without anosmia; results in Kallmann syndrome in the presence of NSMF mutation Ala-480; 25 to 35% reduction in enzymatic activity compared to wild-type.
Abolishes interaction with histone H3K9me3 and prevents recruitment of the HUSH complex to heterochromatin. Impaired ability to mediate silencing of unintegrated retroviral DNA.
In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164 and A-385.
In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-164; and A-334.
In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-149; A-334 and A-385.
In STA mutant; fails to dissociate from chromatin during early mitosis; when associated with A-164; A-334 and A-385.
EP300-interacting inhibitor of differentiation 3
Abolishes ion transport across the cell membrane.
Abolishes localization at early endosomes and leads to localization at late endosomes and lysosomes.
Decreases affinity for divalent metal cations. Impairs ion transport across the cell membrane.
In AHMIO1; increased skipping of exon 12.
Natural resistance-associated macrophage protein 2
Variants Del 98-Cys--Pro-105 and Val-149.
Melanin-concentrating hormone receptor 2
No changes in receptor binding or functional signaling.
Abolished binding to C-degron with an arginine at the C-terminus.
Modifies specificity for C-degron at the C-terminus and promotes increased affinity for C-degrons usually recognized by FEM1B; when associated with A-183--F-188.
Modifies specificity for C-degron at the C-terminus and promotes increased affinity for C-degrons usually recognized by FEM1B; when associated with N-150.
Nearly abolished binding to C-degron with an arginine at the C-terminus.
Reduced binding to C-degron with an arginine at the C-terminus.
Reduced binding to C-degron with an arginine at the C-terminus. Abolished binding to C-degron with an arginine at the C-terminus; when associated with A-126.
Reduced binding to C-degron with an arginine at the C-terminus. Abolished binding to C-degron with an arginine at the C-terminus; when associated with A-77.
Strongly reduced binding to C-degron with an arginine at the C-terminus.
Coiled-coil domain-containing protein 184
Spermatid perinuclear RNA-binding protein
In a patient with amyotrophic lateral sclerosis.
DNA-directed RNA polymerases I, II, and III subunit RPABC4
In UHS1; forms large aggregates; decreases protein-arginine deiminase activity.
No effect on EMC assembly and no effect on membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC.
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC; when associated S-101, S-106 and S-110.
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC; when associated S-101, S-106 and S-111.
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC; when associated S-101, S-110 and S-111.
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC; when associated S-106, S-110 and S-111.
Abolishes CDK2-induced activity in the absence, but not in the presence, of progestin. Delayed nuclear translocation in presence of progestin.
Decreases protein stability and increases progesterone-induced transcriptional activity.
Great loss of sumoylation; when associated with R-7. Completely abolishes sumoylation; when associated with R-7 and R-531. Loss of CUEDC2-mediated protein degradation. Increased ligand-dependent transcriptional activity.
No change in progestin-induced protein degradation; when associated with A-344. No change in sumoylation; when associated with A-294 and A-344.
No effect on interaction with CUEDC2. Impaired progesterone-induced transcriptional activity. No CUEDC2- nor progestin-mediated protein degradation. No change in sumoylation; when associated with A-344 and A-345.
No interaction with SP1. No change in progestin-induced protein degradation; when associated with A-345. No change in sumoylation; when associated with A-294 and A-345.
Reduces transcriptional activation; when associated with A-115 and A-118.
Reduces transcriptional activation; when associated with A-115 and A-119.
Reduces transcriptional activation; when associated with A-118 and A-119.
Reduces transcriptional activation; when associated with A-55 and A-58.
Reduces transcriptional activation; when associated with A-55 and A-59.
Reduces transcriptional activation; when associated with A-58 and A-59.
Some loss of sumoylation; when associated with R-531. Complete loss of sumoylation; when associated with R-388 and R-531.
Some loss of sumoylation; when associated with R-7. Completely abolishes sumoylation; when associated with R-7 and R-388.
FXYD domain-containing ion transport regulator 7
Chloride intracellular channel protein 4
Tumor necrosis factor ligand superfamily member 10
Loss of E3 ubiquitin protein ligase activity.
In BOR2; affects Eya1 binding and the ability to activate gene transcription.
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1
Loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with A-343.
Loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with A-344.
Abolishes interaction with ATG13; when associated with D-152 and D-152.
Abolishes interaction with ATG13; when associated with D-152 and D-156.
Abolishes interaction with ATG13; when associated with D-153 and D-156.
Impairs interaction with ATG13; when associated with R-54.
Impairs interaction with ATG13; when associated with S-31.
Golgin subfamily A member 6-like protein 6
Sodium/potassium-transporting ATPase subunit beta-1
In DFNB107; unknown pathological significance.
Loss of coactivator activity in presence of estrogen.
No effect on phosphorylation induced by EGF.
Strongly decreases phosphorylation induced by EGF. Abolishes phosphorylation in response to EGF, estrogen and progesterone; when associated with F-231.
In LGMDR3; associated with P-G-A-Q-P-136 ins.
Intraflagellar transport protein 57 homolog
Pre-rRNA-processing protein TSR1 homolog
Inhibits axonal and dendritic filopodia formation and reduces dendritic and axonal branching.
Found in two patients with Kufor-Rakeb syndrome also carrying R-877 in ATP13A2.
In PARK15; no effect on interaction with PRKN.
In PARK15; unknown pathological significance.
Abolishes interaction with histone H3.3.
Abolishes interaction with histones H3 and H4.
Abolishes sumoylation; when associated with A-630.
Abolishes sumoylation; when associated with A-631.
Impairs interaction with histones H3 and H4.
No effect on cytosol translocation. upon glucose deprivation.
No translocation to the cytosol upon glucose deprivation.
Impairs interaction with NUP214 and RNA.
Constitutively active. Increased receptor signaling pathway via JAK-STAT.
In AIIDE; constitutive gain of function resulting in increased receptor signaling pathway via JAK-STAT; no effect on protein abundance.
In AIIDE; increased activation of protein kinase activity; constitutive gain of function through the transactivation of associated JAK kinases; increased receptor signaling pathway via JAK-STAT.
Loss of protein tyrosine kinase activity.
Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with E-35.
Alters specificity of protein interaction and enhances pro-apoptotic activity; when associated with I-32.
Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-32.
Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-29 and E-36.
Loss of interaction with MCL1 and of increased MCL1 degradation; when associated with E-32 and E-32.
Phorbol-12-myristate-13-acetate-induced protein 1
In CMT2FF; results in misfolding due to the creation of a non-native disulfide bond with C-152.
Ras association domain-containing protein 7
In TDH2A; fails to localize to the plasma membrane.
In TDH2A; partial defect; expressed on the plasma membrane surface at less than half the rate of wild-type enzyme.
In TDH2A; partial defect; expression slightly lower in efficiency and more degenerative than wild-type enzyme.
In TDH2A; unknown pathological significance.
In isoform 2, isoform 2-3, isoform 2-4 and isoform 6.
Abolishes the ability to induce epidermal terminal differentiation; when associated with A-27.
Abolishes the ability to induce epidermal terminal differentiation; when associated with A-30.
Abolishes the ability to induce epidermal terminal differentiation; when associated with A-39.
Abolishes the ability to induce epidermal terminal differentiation; when associated with A-43.
Cyclin-D-binding Myb-like transcription factor 1
AT-rich interactive domain-containing protein 2
39S ribosomal protein L49, mitochondrial
Sodium-coupled neutral amino acid transporter 5
tRNA wybutosine-synthesizing protein 3 homolog
Loss of kinase activity. In isoform 1, excluded from the nucleus. No effect on microtubule-binding.
Loss of kinase activity; No effect on MAP3K7-mediated activation of NF-kappa-B.
No effect on kinase activity, nor on JNK activation, but severe reduction in nuclear localization and apoptotic membrane blebbing.
39S ribosomal protein L36, mitochondrial
Age-related maculopathy susceptibility protein 2
UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1
Abolished tRNA pseudouridine synthase without affecting ability to promote miRNA processing.
In JABELS; unknown pathological significance.
Glucose-6-phosphatase catalytic subunit 1
In GSD1A; complete loss of glucose-6-phosphatase activity and reduced enzyme stability.
In GSD1A; complete loss of glucose-6-phosphatase activity.
In GSD1A; complete loss of glucose-6-phosphatase activity; prevalent mutation in Ashkenazi Jewish population.
In GSD1A; loss of catalytic glucose-6-phosphatase activity.
Partial loss of glucose-6-phosphatase activity.
Calmodulin-binding transcription activator 2
In BBS19; loss-of-function mutation; results in significantly reduced protein levels.
Intraflagellar transport protein 27 homolog
Abolishes ATP-binding and localizes to cytoplasm.
Abolishes sumoylation and localization to tubular structures of the ERC, impairs fast recycling activity from the ERC, no effect on homooligomerization; when associated with R-511.
Abolishes sumoylation localization to tubular structures of the ERC, impairs fast recycling activity from the ERC, no effect on homooligomerization;; when associated with R-315.
Greatly reduces oligomerization and interaction with RAB11FIP2.
Associated with lower sodium concentrations in serum; shows diminished response to hypotonic stress relative to wild-type.
Found in a patient with spondyloepiphyseal dysplasia Maroteaux type.
Found in a patient with spondyloepiphyseal dysplasia Maroteaux type; decreased protein stability; increased ATP-binding.
In BCYM3; results in a gain of function and a constitutive activation of the channel.
In CMT2C and SPSMA; decreased protein stability; decreased ATP-binding.
In CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; decreases protein stability; causes increased cell death.
In CMT2C; increased agonist-induced channel activity; causes increased cell death; no effect on protein stability and ATP-binding.
In CMT2C; increased basal and agonist-induced channel activity, decreased protein stability; decreased ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death.
In FDAB; poorly expressed on the cell surface; mutant channels show a significantly reduced response to agonists.
In HMN8 and CMT2C; does not affect channel localization to plasma membrane; results in increased agonist-induced channel activity and increased basal intracellular calcium concentration; decreases ATP-binding; no effect on protein stability; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death.
In HMN8 and CMT2C; increased agonist-induced channel activity and increased basal intracellular calcium concentration; slightly decreased protein stability and ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death.
In MTD and SMDK; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type.
In MTD; also found in a patient with spondyloepiphyseal dysplasia Maroteaux type.
In MTD; decreased protein stability; decreased ATP-binding.
In MTD; decreased protein stability; no effect on ATP-binding.
In MTD; impairs protein folding or stability.
In MTD; lethal form; decreased protein stability; reduced ATP-binding.
In MTD; no effect on protein stability; no effect on ATP-binding.
In SMDK; decreased protein stability; no effect on ATP-binding.
In SMDK; slightly increased ATP-binding; slightly decreased protein stability.
Loss of Ca(2+) dependent current potentiation.
Loss of Ca(2+) influx. Loss of DDX3X translocation to the nucleus.
Loss of calmodulin binding; when associated with 816-ELEEDE-821.
Loss of calmodulin binding; when associated with A-828.
Loss of interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate; when associated with P-299.
No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate.
Strongly decreased interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate. Loss of interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate; when associated with D-296.
Transient receptor potential cation channel subfamily V member 4
In AGM9; decreased zinc ion transporter activity; does not affect localization to endoplasmic reticulum.
In AGM9; unknown pathological significance.
Loss of phosphorylation in response to Zn(2+) treatment and of cytosolic Zn(2+) release; when associated with A-275.
Loss of phosphorylation in response to Zn(2+) treatment and of cytosolic Zn(2+) release; when associated with A-276.
In MRT52; no effect on general protein glycosylation.
Found in an oligozoospermic man; unknown pathological significance.
Transcription initiation factor TFIID subunit 7-like
CKLF-like MARVEL transmembrane domain-containing protein 4
Eukaryotic translation initiation factor 2 subunit 2
Zinc finger FYVE domain-containing protein 21
Sodium-dependent phosphate transport protein 2C
Patatin-like phospholipase domain-containing protein 4
In CMD1M; unknown pathological significance; decreases interaction with TCAP.
In CMD1M; unknown pathological significance; increases PKC/PRKCA activity.
In CMH12; decreases interaction with NRAP and ACTN2, decreases zinc-binding and impairs protein stability, decreases PKC/PRKCA activity.
In FERLK; risk factor for erythroleukemia; results in increased ERBB-mediated signaling; results in a block of erythroid differentiation and increased cell proliferation.
In VSCN1; almost complete loss of ERBB2 and ERBB3 phosphorylation in the presence or in the absence of NRG1 stimulation, suggesting alteration of downstream signaling; does not affect the subcellular localization at the cell membrane.
In VSCN1; unknown pathological significance; some decrease in ERBB2 phosphorylation upon NG1 treatment, compared to wild-type; does not affect the subcellular localization at the cell membrane.
Strongly reduced tyrosine phosphorylation.
5-glutamyl glycerylphosphorylethanolamine
N6,N6,N6-trimethyllysine; alternate; by EEF1AKMT3
N6,N6,N6-trimethyllysine; alternate; by EEF1AKMT4
N6,N6-dimethyllysine; alternate; by EEF1AKMT3
N6,N6-dimethyllysine; alternate; by EEF1AKMT4
N6-methyllysine; alternate; by EEF1AKMT3
N6-methyllysine; alternate; by EEF1AKMT4
No effect on methylation by EEF1AKMT2. Abolishes EEF1AKMT4-mediated methylation.
No effect on methylation by EEF1AKMT2. Abolishes methylation by METTL13.
Resistant to inhibition by plitidepsin. No effect on SARS-CoV-2 proteins translation.
In XLID12; normal amounts of mutant protein; normal amounts of other THO complex subunits.
In XLID12; reduced amounts of mutant protein; reduced amounts of other THO complex subunits; the mutant protein has a significantly shorter half-life.
In XLID12; reduced amounts of protein; reduced amounts of other THO complex subunits; the mutant protein has a significantly shorter half-life.
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6 and isoform 7.
In isoform 2, isoform 3, isoform 6 and isoform 7.
In isoform 2, isoform 4, isoform 5 and isoform 7.
Mitochondrial inner membrane protease subunit 1
In CLN4B; results in near absence of palmitoylated monomeric forms of the protein and formation of high molecular mass aggregates with diffuse intracellular localization.
Decreases RNA primer di-nucleotide formation about 5-fold. Does not affect the ratio between the di-nucleotide and its extension products.
Decreases primase affinity for POLA1 by 10-fold.
Decreases primase affinity for POLA1 by 30-fold.
Decreases primase affinity for POLA1 by 40-fold.
In PV, THCYT3 and AML; associated with susceptibility to Budd-Chiari syndrome; somatic mutation in a high percentage of patients with essential thrombocythemia or myelofibrosis; leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity.
In myeloproliferative disorder with erythrocytosis.
In myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions.
Loss of kinase activity. Does not promote GLI1 nuclear localization.
Decreased transcription factor activity due to impaired interaction with ARNT2.
Decreased transcription factor activity.
Does not affect the transcription factor activity.
Likely benign variant; does not affect the transcription factor activity.
Neuronal PAS domain-containing protein 4
Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta
Found in blue naevi and uveal melanoma samples; somatic mutation; constitutive activation.
Guanine nucleotide-binding protein G(q) subunit alpha
In SWS; found as somatic mosaic mutation in CMC; also found in melanocytomas sample; somatic mutation; shows significant activation of EPHB2 compared to control.
Reduces binding to Drosophila crb and causes incorrect PALS1 localization and cell polarity.
Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase
In NEDDFSA; leads to altered positioning of pyramidal neurons.
In NEDDFSA; leads to altered positioning of pyramidal neurons; decreased transcription coactivator activity; does not affect nuclear localization.
In NEDDFSA; unknown pathological significance.
Zinc finger MIZ domain-containing protein 1
Coiled-coil-helix-coiled-coil-helix domain-containing protein 7
Impaired SDCBP-mediated interaction with phosphatidylinositol-4,5-bisphosphate.
In OI17; decreased secretion of the protein; altered secretion of procollagen type I.
In OI17; no effect on expression and secretion of the protein; altered secretion of procollagen type I.
Found in a MVP2 patient also carrying pathogenic mutation H-2513; has no significant effect on protein levels.
In MVP2; loss-of-function mutation; results in reduced protein levels; results in increased protein degradation.
In MVP2; the patient also carries L-197; loss-of-function mutation; results in reduced protein levels; results in increased protein degradation.
7SK snRNA methylphosphate capping enzyme
Abolished methyltransferase activity and reduced interaction with LARP7, without affecting interaction with P-TEFb.
Nearly abolished methyltransferase activity.
Strongly reduced methyltransferase activity.
Cytoplasmic; when associated with A-273.
Cytoplasmic; when associated with A-276.
Coiled-coil domain-containing protein 89
Decreases interaction with STT3A, STT3B and RPN1.
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 4
LHFPL tetraspan subfamily member 6 protein
Endosome-associated-trafficking regulator 1
Abolishes phosphorylation by PKD and the interaction with 14-3-3 proteins.
Sodium-dependent phosphate transport protein 1
Abolishes cleavage by CASP1 and impairs ability to antagonize apoptosis-induced immune tolerance.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-181.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-53.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-53 and E-181.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-46; E-53 and E-181.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-42; E-46; E-53 and E-181.
Cytoplasmic localization (phosphorylation mimicking); when associated with E-39; E-42; E-46; E-53 and E-181.
Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-181.
Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-46 and A-53.
Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-42; A-53 and A-181.
Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-39; A-46; A-53 and A-181.
Greatly reduces phosphorylation, nuclear localization; when associated with A-35; A-42; A-46; A-53 and A-181.
Greatly reduces phosphorylation, nuclear localization; when associated with A-39; A-42; A-46; A-53 and A-181.
Inhibits oxidation-dependent inactivation of immunostimmulatory activity in apoptotic cells.
Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-?)
Abolishes CDE RNA-binding but no effect on dsRNA binding.
In IMDYSHI; decreased protein abundance; loss of localization to P-bodies; decreased interaction with CCR4-NOT deadenylase complex; loss of function in regulation of deadenylation-dependent decapping of nuclear-transcribed mRNA; failed to regulate the production of inflammatory cytokines.
No effect on CDE RNA-binding but abolishes dsRNA binding; when associated with 135-E-E-136.
No effect on CDE RNA-binding but abolishes dsRNA binding; when associated with E-164 or A-322-323-A.
Slightly reduces stem-loop RNA and dsRNA binding.
Strongly decreases binding to RNA containing CDE stem-loop motifs. Abolishes binding to RNA containing CDE stem-loop motifs and dsRNA; when associated with 219-A-A-220.
Strongly decreases binding to RNA containing CDE stem-loop motifs. Abolishes binding to RNA containing CDE stem-loop motifs and dsRNA; when associated with 259-A-A-260.
1-(tryptophan-3-yl)-tryptophan (Trp-Trp) (interchain with W-33)
Abolishes dimerization; when associated with E-50 and E-51.
Abolishes dimerization; when associated with Q-134.
Destabilization of dimer and loss of zinc binding; when associated with S-81.
Destabilization of dimer and loss of zinc binding; when associated with S-84.
Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-58; S-112 and S-147.
Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-7; S-112 and S-147.
Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-7; S-58 and S-112.
Enhances formation of fibrillar aggregates in the absence of bound zinc; when associated with S-7; S-58 and S-147.
In ALS1; 'benign' form; 80% of wild-type activity; ubiquitinated by RNF19A.
In ALS1; destabilizes dimeric protein structure and increases tendency to form fibrillar aggregates.
In ALS1; does not seem to be linked with a decrease in activity.
In ALS1; increases tendency to form fibrillar aggregates.
In ALS1; increases tendency to form fibrillar aggregates; ubiquitinated by RNF19A.
In ALS1; mild form; ubiquitinated by RNF19A. Ubiquitinated by MARCH5; leading to the degradation of mitochondrial SOD1.
In ALS1; reduced metal binding; increases tendency to form fibrillar aggregates.
In ALS1; reduces structural stability and enzyme activity; increases tendency to form fibrillar aggregates.
In ALS1; reduces tendency to form fibrillar aggregates.
In ALS1; severe form; reduces structural stability and enzyme activity; increases tendency to form fibrillar aggregates.
In ALS1; sporadic form; interferes with zinc binding; requires 2 nucleotide substitutions.
In ALS1; ubiquitinated by RNF19A; interferes with zinc-binding; ubiquitinated by MARCH5; leading to the degradation of mitochondrial SOD1.
Loss of zinc binding and enhanced tendency to form aggregates; when associated with A-81.
Loss of zinc binding and enhanced tendency to form aggregates; when associated with A-84.
Mimicks constitutive succinylation state; decreased activity.
No palmitoylation, reduced nuclear targeting.
Leucine-rich repeat-containing protein 40
No GTP binding. No GTP binding; when associated with T-45.
No GTP binding; when associated with G-25.
Abolishes gamma-glutamyltranspeptidase activity.
Abolishes gamma-glutamyltranspeptidase activity. Increases KM for D-gamma-glutamyl-p-nitroanalide by over 1000-fold.
Loss of autocatalytic cleavage, cell membrane localization and decrease in gamma-glutamyltranspeptidase activity; when associated with W-192.
Loss of autocatalytic cleavage, cell membrane localization and decrease in gamma-glutamyltranspeptidase activity; when associated with Y-193.
No effect on gamma-glutamyltranspeptidase activity.
Reduces enzyme gamma-glutamyltranspeptidase activity by 90%.
Reduces enzyme gamma-glutamyltranspeptidase activity by 99%.
Reduces gamma-glutamyltranspeptidase activity by 66%.
Reduces gamma-glutamyltranspeptidase activity by 90%.
Reduces gamma-glutamyltranspeptidase activity by 98%.
Reduces gamma-glutamyltranspeptidase activity by 99%. Abolishes activity; when associated with A-451.
Reduces gamma-glutamyltranspeptidase activity by 99%. Abolishes activity; when associated with A-452.
Osteoclast-associated immunoglobulin-like receptor
Carcinoembryonic antigen-related cell adhesion molecule 8
Does not affect the monomeric structure. Decreases heterodimerization with CEACAM6.
Does not affect the monomeric structure. Loss of heterodimerization with CEACAM6.
No effect on heterophilic cell adhesion.
2-(3-amino-3-carboxypropyl)histidine synthase subunit 2
Found in a patient with diphthamide-deficiency syndrome; probable disease-associated variant; severely impairs diphthamide modification of elongation factor 2..
L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase
Reduces affinity for magnesium and coenzyme A, and reduces holo-[acyl-carrier-protein] synthase activity by 7-fold.
Reduces affinity for magnesium by 10-fold, and holo-[acyl-carrier-protein] synthase activity by 30000-fold.
Reduces affinity for magnesium by 20-fold, and holo-[acyl-carrier-protein] synthase activity by 6500-fold.
Reduces affinity for magnesium by 200-fold and abolishes holo-[acyl-carrier-protein] synthase activity; when associated with Q-181.
Reduces affinity for magnesium by 40-fold, and holo-[acyl-carrier-protein] synthase activity by 32000-fold.
Reduces affinity for magnesium by 7-fold, and holo-[acyl-carrier-protein] synthase activity by 2-fold.
Reduces affinity for magnesium by 75-fold, and holo-[acyl-carrier-protein] synthase activity by 150-fold.
Reduces holo-[acyl-carrier-protein] synthase activity by 2000-fold, with only minor change in the affinity for magnesium and coenzyme A.
Does not affect leukotriene-C4 synthase activity but substantially increased KM for GSH.
Leukotriene-C4 synthaseactivity is reduced by 30%.
Loss of leukotriene-C4 synthase activity.
Reduced leukotriene-C4 synthase activity by nearly 80%.
Reduces Leukotriene-C4 synthase activity and increases the optimum for pH-dependent activity.
Acidic leucine-rich nuclear phosphoprotein 32 family member A
Complete loss of phosphorylation; when associated with A-158.
Complete loss of phosphorylation; when associated with A-204.
Loss of interaction with influenza virus A PB2.
Aldehyde dehydrogenase family 1 member A3
In MCOP8; does not affect ALDH1A3 expression; results in strongly reduced protein levels.
Abolishes GTPase activity and decreases association with GPN3.
Found in a patient with obliterative portal venopathy; unknown pathological significance.
Found in patients with obliterative portal venopathy; unknown pathological significance.
Decreases arachidonate release from cell membranes; when associated with E-112.
Decreases arachidonate release from cell membranes; when associated with E-113.
Impairs arachidonate release from cell membranes.
Does not affect phosphorylation state and enzymatic activity.
Non-receptor tyrosine-protein kinase TYK2
Reduces basal catalytic activity and abolishes IFN-dependent activation.
In CSS10; loss DNA-binding transcription factor activity.
In CSS10; loss of DNA-binding transcription factor activity.
Abolishes binding to ubiquitin. Abolishes binding to ubiquitin; when associated with A-150.
Abolishes binding to ubiquitin; when associated with A-147.
Fanconi anemia core complex-associated protein 20
Probable phospholipid-transporting ATPase IIA
Abolishes binding to 'Lys-15'-acetylated histone H3.
No effect on binding to 'Lys-15'-acetylated histone H3.
General transcription factor 3C polypeptide 6
3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic
Abolishes myristoylation and induces a subcellular location change.
In MCCCHCM; expression of this variant in transgenic mice results in thicker corpus callosum, hypoplastic cortex and hypoplastic cerebellum.
In MCCCHCM; unknown pathological significance.
In a patient with neurodevelopmental abnormalities; de novo variant; unknown pathological significance.
Microtubule-associated serine/threonine-protein kinase 1
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)
Instead of the formation of an intermediate complex with a thiol ester bond between ATG3 (E2-like enzyme) and GABARAPL1/APG8L (substrate), a stable complex with an O-ester bond is formed.
Impairs interaction with PLK4; impaired procentriole assembly and chromosome segregation.
In COXPD21; decreased expression at mRNA and protein levels; decreased threonine-tRNA ligase activity; affects both Thr activation and transfer; decreased aminoacyl-tRNA editing activity; decreased protein stability; loss of homodimerization.
S-adenosylmethionine synthase isoform type-2
Clathrin heavy chain linker domain-containing protein 1
In allele CYP2B6*2 and allele CYP2B6*10.
In allele CYP2B6*4, allele CYP2B6*6, allele CYP2B6*7 and allele CYP2B6*13; slight decrease in activity.
In allele CYP2B6*6, allele CYP2B6*7, allele CYP2B6*9 and allele CYP2B6*13.
In allele CYP2B6*8 and allele CYP2B6*13.
In BLAUS and IBD1; unknown pathological significance.
In BLAUS; atypical form with cardiac infiltration; sporadic case; unknown pathological significance; hyperactive.
In BLAUS; no disruption of NOD2-CARD9 interaction; hyperactive.
In BLAUS; somatic mosaicism in 4.9% to 11% of peripheral blood cells; hyperactive; abolishes interaction with LDOC1, ANKHD1, PPP2R3B, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5.
In BLAUS; unknown pathological significance; hyperactive.
In BLAUS; unknown pathological significance; not hyperactive.
In IBD1 and YAOS; associated with disease susceptibility; decreases half-life of protein; abolishes interaction with ANKHD1, ENTR1 and TRIM41; decreases interaction with RIPK2 and PPP1R12C; no effect on interaction with CHMP5, LDOC1 and PPP2R3B.
In IBD1 and YAOS; associated with disease susceptibility; no disruption of NOD2-CARD9 interaction; decreases half-life of protein; abolishes interaction with ANKHD1, ENTR1 and TRIM41; increases interaction with RIPK2 and PPP2R3B; decreases interaction with LDOC1 and PPP1R12C; no effect on interaction with CHMP5.
In IBD1; also found in patients with ulcerative colitis; unknown pathological significance.
In IBD1; unknown pathological significance.
In IBD1; unknown pathological significance; no disruption of NOD2-CARD9 interaction.
No disruption in NOD2-CARD9 interaction.
No disruption of NOD2-CARD9 interaction.
Nucleotide-binding oligomerization domain-containing protein 2
Ubiquitin carboxyl-terminal hydrolase 48
EF-hand domain-containing family member C2
Abolished binding to histone H3 crotonylated at 'Lys-27' (H3K27cr).
Reduced binding to histone H3 crotonylated at 'Lys-27' (H3K27cr).
Strongly reduced binding to histone H3 crotonylated at 'Lys-27' (H3K27cr).
Vitelline membrane outer layer protein 1 homolog
85-fold reduction in activity. Uncouples the glycosylase activity from the lyase activity. Shows glycosylase activity without any detectable AP-lyase activity during the first 10 min of the reaction.
Benign variant; no effect on homologous recombination-mediated DNA repair; no effect on interaction with SEM1.
Benign variant; no effect on homology-directed repair activity.
Breast cancer type 2 susceptibility protein
In BC and ovarian cancer; unknown pathological significance.
In BC and ovarian cancer; unknown pathological significance; no effect on homology-directed repair activity.
In BC; abolishes interaction with PALB2.
In BC; also found in pancreatic cancer; decreased homology-directed repair activity.
In BC; benign variant; no effect on homology-directed repair activity.
In BC; has defective function consistent with pathogenicity; major splicing aberration identified with this mutant; reduced homology-directed repair activity.
In BC; has defective function consistent with pathogenicity; multifactorial likelihood analysis provides evidence for pathogenicity; reduced homology-directed repair activity.
In BC; reduced homology-directed repair activity.
In BC; unknown pathological significance.
In BC; unknown pathological significance; decreased homology-directed repair activity.
In BC; unknown pathological significance; disrupts interaction with SEM1 promoting interaction with XPO1 and BRCA2 cytoplasmic localization; in heterozygous state promotes RAD51 cytoplasmic localization; reduced homology-directed repair activity.
In BC; unknown pathological significance; no effect on homologous recombination-mediated DNA repair; no effect on interaction with SEM1.
In BC; unknown pathological significance; no effect on homology-directed repair activity.
In BC; unknown pathological significance; reduced homology-directed repair activity.
In FANCD1; affects protein splicing and expression; decreases homologous recombination-mediated DNA repair.
In FANCD1; hypersensitive to DNA damage; disrupts interaction with SEM1; decreased homology-directed repair activity.
In FANCD1; hypersensitive to DNA damage; reduced homology-directed repair activity; no effect on interaction with SEM1.
In a patient with ovarian cancer; unknown pathological significance; no effect on homology-directed repair activity.
In one patient with BC; normal RNA expression and splicing.
In one patient with esophageal carcinoma.
In one patient with esophageal carcinoma; somatic mutation.
In one patient with esophageal carcinoma; somatic mutation; decreased homology-directed repair activity.
In ovarian cancer and BC; somatic mutation; unknown pathological significance; small decrease of homology-directed repair activity.
In ovarian cancer and renal cancer; unknown pathological significance.
In ovarian cancer; unknown pathological significance.
Loss of phosphorylation by CHEK1 and CHEK2 (in vitro).
Nuclear export signal; masked by interaction with SEM1
Probable disease-associated variant; may be associated with cancer susceptibility; major splicing aberration identified with this mutant; multifactorial likelihood analysis provides evidence for pathogenicity.
Eliminates VIC formation and association with VP16. Unable to rescue proliferation in temperature-sensitive arrested cells.
Eliminates VIC formation and association with VP16. Weak association with POU2F1. Unable to associate with CREBZF and BAP1. Unable to rescue proliferation in temperature-sensitive arrested cells.
Eliminates VIC formation, but only minor reduction in association with VP16. Unable to associate with POU2F1, but only minor reduction in association with CREB3. Able to rescue proliferation in temperature-sensitive arrested cells.
Eliminates VIC formation. Unable to rescue proliferation in temperature-sensitive arrested cells.
In MAHCX; unknown pathological significance.
Minor reduction in VIC formation and association with VP16 and CREB3. Able to rescue proliferation in temperature-sensitive arrested cells.
Minor reduction in VIC formation and association with VP16. Weak association with POU2F1. Severely reduces association with CREB3. Able to rescue proliferation in temperature-sensitive arrested cells.
Minor reduction in VIC formation, but retains association with VP16. Unable to rescue proliferation in temperature-sensitive arrested cells.
Moderately reduces VIC formation and association with VP16 and CREB3. Unable to rescue proliferation in temperature-sensitive arrested cells.
Moderately reduces association with VP16 and CREB3. Able to rescue proliferation in temperature-sensitive arrested cells.
Reduces and disrupts cleavage at HCF repeat.
Severely reduces VIC formation, but retains association with VP16. Severely reduces association with CREB3. Unable to rescue proliferation in temperature-sensitive arrested cells.
Severely reduces VP16-induced complex (VIC) formation, but retains association with VP16. Unable to rescue proliferation in temperature-sensitive arrested cells. Abolishes interaction with CREB3.
Abolishes histone H4 binding and methyltransferase activity.
Alters methyltransferase activity, so that both monomethylation and dimethylation take place.
Does not affect the interaction with SIRT2. Increases the number of mitotic foci formation. Does not affect methyltransferase activity.
Increases the interaction with SIRT2. Reduces the number of mitotic foci formation. Does not affect methyltransferase activity.
Strongly decreases methyltransferase activity.
Strongly reduces affinity for histone H4 and abolishes methyltransferase activity.
Strongly reduces affinity for histone H4 and methyltransferase activity.
Strongly reduces affinity for histone H4.
In MCPH24; reduced mutant protein levels; impairs assembly of nuclear pore complex as indicated by lower number of nuclear pores in patient fibroblasts.
Histone deacetylase complex subunit SAP30
Disrupts interaction with CEP290, no effect on interaction with BBS1, BBS2, BBS4, BBS8 and BBS9, abolishes ciliogenesis.
IQ calmodulin-binding motif-containing protein 1
Abolished interaction with NFE2L2/NRF2; when associated with 123-A--A-127.
Abolished interaction with NFE2L2/NRF2; when associated with 161-A-A-162.
Abolishes repression of NFE2L2/NRF2-dependent gene expression.
Abolishes repression of NFE2L2/NRF2-dependent gene expression. Slows down degradation of NFE2L2/NRF2.
In a NSCLC cell line; strongly reduces interaction with NFE2L2/NRF2 and reduces repression of NFE2L2/NRF2-dependent gene expression.
In a lung adenocarcinoma cell line; also in NSCLC cell lines; strongly reduces interaction with NFE2L2/NRF2 and reduces repression of NFE2L2/NRF2-dependent gene expression.
In a lung adenocarcinoma patient; somatic mutation; strongly reduces interaction with NFE2L2/NRF2 and reduces repression of NFE2L2/NRF2-dependent gene expression.
Increases ubiquitination and proteolytic degradation.
Loss of export from nucleus; when associated with A-308.
Loss of export from nucleus; when associated with A-310.
Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Does not affect interaction with SQSTM1/p62.
Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Impaired interaction with SQSTM1/p62.
Loss of interaction with NFE2L2/NRF2. Abolishes repression of NFE2L2/NRF2-dependent gene expression. Loss of interaction with PGAM5. Does not affect interaction with SQSTM1/p62.
Loss of interaction with NFE2L2/NRF2. Strongly reduces repression of NFE2L2/NRF2-dependent gene expression. Abolishes interaction with SQSTM1/p62.
Loss of interaction with NFE2L2/NRF2. Strongly reduces repression of NFE2L2/NRF2-dependent gene expression. Impaired interaction with SQSTM1/p62.
Loss of interaction with NFE2L2/NRF2. Strongly reduces repression of NFE2L2/NRF2-dependent gene expression. Loss of interaction with PGAM5.
Loss of interaction with NFE2L2/NRF2. Strongly reduces repression of NFE2L2/NRF2-dependent gene expression. Loss of interaction with PGAM5. Abolishes interaction with SQSTM1/p62.
N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Arg-Cys) (interchain with C-151 in KEAP1)
N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Cys-Arg) (interchain with R-135 in KEAP1)
Reduced formation of a high-molecular mass KEAP1 molecule when methylglyoxal accumulates.
S-(2,3-dicarboxypropyl)cysteine; alternate
Substitution with a bulky side chain that mimicks covalent modification by an electrophile; prevents ubiquitination and degradation of NFE2L2/NRF2, leading to constitutive activation of NFE2L2/NRF2 and subsequent expression of phase 2 detoxifying enzymes.
Substitution with a small side chain that prevents covalent modification by an electrophile; promotes constitutive ubiquitination of NFE2L2/NRF2 and subsequent repression of phase 2 detoxifying enzymes. Resistance of ubiquitination of PGAM5 to inhibition by oxidative stress and sulforaphane. Impaired interaction with CUL3. Reduced formation of a high-molecular mass KEAP1 molecule when methylglyoxal accumulates.
Loss of in vitro protein phosphatase activity.
No effect on in vitro protein phosphatase activity.
Vacuolar protein sorting-associated protein 29
In PRLTS2; the mutant protein is expressed, can dimerize and localizes to the mitochondria; has significantly decreased enzymatic activity compared to wild-type.
In PRLTS2; unknown pathological significance.
In ABOLM; unknown pathological significance; loss of expression in skin and mucosa.
Synapse differentiation-inducing gene protein 1-like
Decreases binding to the pro-C3-convertase complex. Does not affect Complement C3 beta chain binding.
In AHUS4; gain-of-function mutation that results in enhanced formation of the C3bBb.
In allele FA; requires 2 nucleotide substitutions.
In allele S; may be associated with a reduced risk for age-related macular degeneration.
May be associated with a reduced risk for age-related macular degeneration.
In SCA46; unknown pathological significance; reduced lysosomal localization; induces retention in the ER; reduction of proteolityc cleavage; loss of exonuclease activity.
Originally reported as risk factor for Alzheimer disease; unknown pathological significance; does not reduce either amyloid-beta levels or APP expression.
Slightly increased plasma membrane localization, does not affect delivery to lysosomes.
Found in a patient with atypical hemolytic uremic syndrome.
Found in patients with atypical hemolytic uremic syndrome.
CAP-Gly domain-containing linker protein 3
Inhibits interaction with ZDHHC13 and ZDHHC17.
Strongly reduced plasma membrane association and decrease in the levels of Akt at the plasma membrane.
In A1 mutant; abolished ATP-binding; decreased interaction with PEX1 or PEX26.
In A2 mutant; abolished ATP-binding; decreased interaction with PEX1 or PEX26.
In B1 mutant; abolished ATP hydrolysis; does not affect interaction with PEX6 or PEX26.
In B2 mutant; does not affect interaction with PEX6 or PEX26.
In HMLR2; results in mild functional decrease in peroxisome biogenesis.
In HMLR2; results in severe functional decrease in peroxisome biogenesis.
In HMLR2; unknown pathological significance.
In HMLR2; unknown pathological significance; results in mild functional decrease in peroxisome biogenesis.
In PBD-CG4; disease phenotype includes hearing loss, visual impairment, enamel dysplasia microcephaly with deep white matter changes and developmental delay.
Peptidyl-prolyl cis-trans isomerase-like 3
In SPGF43; loss of protein expression; changed sperm axoneme assembly.
In ANIB12; decreased function in endothelial cell-matrix adhesion; decreased interaction with TLN1.
In ANIB12; loss of function in endothelial cell-matrix adhesion.
In ANIB12; loss of function in endothelial cell-matrix adhesion; undetectable protein expression.
In ANIB12; unknown pathological significance; decreased function in endothelial cell-matrix adhesion; decreased interaction with TLN1.
In ANIB12; unknown pathological significance; loss of function in endothelial cell-matrix adhesion; decreased interaction with TLN1.
Thrombospondin type-1 domain-containing protein 1
Abolishes interaction with RFWD3, leading to impair DNA interstrand cross-links (ICL) repair.
Impaired ubiquitination without affecting homologous recombination.
Increased RAD51 foci formation and homologous recombination efficiency at DNA double-strand breaks; when associated with A-4.
Increased RAD51 foci formation and homologous recombination efficiency at DNA double-strand breaks; when associated with A-8.
Lower homologous recombination efficiency following DNA double strand break. Impaired DNA synthesis following DNA damage; when associated with D-33. No effect on cell-cycle progression, nor DNA synthesis in undamaged cells; when associated with D-23; D-29 and D-33. Impaired DNA double strand breaks repair; when associated with D-23; D-29 and D-33. Extended DNA damage-induced G2-M checkpoint; when associated with D-23; D-29 and D-33. Preferentially interacts with RAD51; when associated with D-23; D-29 and D-33.
Lower homologous recombination efficiency following DNA double strand break. Impaired DNA synthesis following DNA damage; when associated with D-8. No effect on cell-cycle progression, nor DNA synthesis in undamaged cells; when associated with D-8; D-23 and D-29. Impaired DNA double strand breaks repair; when associated with D-8; D-23 and D-29. Extended DNA damage-induced G2-M checkpoint; when associated with D-8; D-23 and D-29. Preferentially interacts with RAD51; when associated with D-8; D-23 and D-29.
No effect on DNA synthesis following DNA damage; when associated with D-23. No effect on cell-cycle progression, nor DNA synthesis in undamaged cells; when associated with D-8; D-23 and D-33. Impaired DNA double strand breaks repair; when associated with D-8; D-23 and D-33. Extended DNA damage-induced G2-M checkpoint; when associated with D-8; D-23 and D-33. Preferentially interacts with RAD51; when associated with D-8; D-23 and D-33.
No effect on DNA synthesis following DNA damage; when associated with D-29. No effect on cell-cycle progression, nor DNA synthesis in undamaged cells; when associated with D-8; D-29 and D-33. Impaired DNA double strand breaks repair; when associated with D-8; D-29 and D-33. Extended DNA damage-induced G2-M checkpoint; when associated with D-8; D-29 and D-33. Preferentially interacts with RAD51; when associated with D-8; D-29 and D-33.
In isoform 1, isoform 2, isoform 3 and isoform 5.
No effect on the structural inability to bind NAD(+); when associated with N-810.
No effect on the structural inability to bind NAD(+); when associated with Y-830.
Zinc finger CCCH-type antiviral protein 1
In BTDD; decreases hydroxylation of the protein; decreases the accuracy of translation; decreases levels of incorporation of the mutant protein into polysomes; patient cells become highly sensitive to oxidative stress.
In BTDD; decreases hydroxylation of the protein; decreases the accuracy of translation; decreases levels of incorporation of the mutant protein into ribosomes and polysomes; patient cells become highly sensitive to oxidative stress.
In NPHS8; produces mislocalization into the nucleus, hyperactivation of Rho-GTPases RHOA, RAC1 and CDC42 and impaired cell motility.
Loss of RHOA interaction; when associated with A-185.
Loss of RHOA interaction; when associated with A-45.
Mitogen-activated protein kinase kinase kinase 4
Loss of glycosylase and lyase activities.
No effect on AP lyase activity. Impairs monofunctional glycosylase activity.
Schiff-base intermediate with DNA; via amino nitrogen
Abolishes interaction with SMN1; Abolishes methylation by PRMT9. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with R-507. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with R-507. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with R-507 and R-509.
Does not affect methylation by PRMT9; when associated with A-506.
Does not affect methylation by PRMT9; when associated with A-510.
Moderately diminished formation of omega-N monomethylarginine but greatly reduced formation of symmetrical dimethylarginine; when associated with A-507.
Moderately diminished formation of omega-N monomethylarginine but greatly reduced formation of symmetrical dimethylarginine; when associated with A-509.
Moderately diminished formation of omega-N monomethylarginine but greatly reduced formation of symmetrical dimethylarginine; when associated with R-507. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with K-508 and R-507.
Moderately diminished formation of omega-N monomethylarginine but greatly reduced formation of symmetrical dimethylarginine; when associated with R-509. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with R-508. Abolishes formation of omega-N monomethylarginine and formation of symmetrical dimethylarginine; when associated with K-508 and R-509.
Omega-N-methylarginine; by PRMT9; alternate
Symmetric dimethylarginine; by PRMT9; alternate
Abolishes the interaction with ARHGEF7. Mutant overexpression in cultured neurons does not induce a significant increase in spine density contrary to wild type.
Abolishes the interaction with DLG1, DLG2, DLG3 and DLG4/PSD95. Reduces protein localization to dendritic spines.
Abolishes the interaction with DLG4/PSD95. Reduces protein localization to dendritic spines.
FERM and PDZ domain-containing protein 4
Nearly abolishes interaction with GPSM2; when associated with 1010-A-A-1011.
Nearly abolishes interaction with GPSM2; when associated with A-990.
Decreases substantially the interaction with PLK4. Weakens binding to PLK4; when associated with E-230 and E-321.
Decreases substantially the interaction with PLK4. Weakens binding to PLK4; when associated with E-230 and E-321. Abolishes the inhibitory effect of TENT5C on the cell viability; when associated with E-320 and E-321.
Does not affect colocalization with PLK4 in centrosome. Increases cell viability.
Slightly decreases the binding to PLK4; when associated with E-320. Abolishes the inhibitory effect of TENT5C on the cell viability; when associated with P-144 and E-320.
Slightly decreases the binding to PLK4; when associated with E-321. Abolishes the inhibitory effect of TENT5C on the cell viability; when associated with P-144 and E-321.
Complement C1q and tumor necrosis factor-related protein 9A
Cyclic AMP-responsive element-binding protein 1
Decreased sumoylation, in vivo and in vitro.
Decreased sumoylation, in vivo and in vitro. Loss of nuclear localization.
Does not interact with TOX3 and inhibits induction of transcription by TOX3. Loss of phosphorylation by CaMK4. Loss of phosphorylation by TSSK4.
Found in a patient with multiple congenital anomalies; does not affect CREB1 phosphorylation at S-119; fails to interact with CREBBP.
Impaired phosphorylation by HIPK2 and subsequent transactivation.
Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5, SGK1 and TSSK4
Reduced CDK5-mediated phosphorylation and impaired dimerization.
Decreases the affinity for IL17RA by 5-fold.
Has no effect on the affinity for IL17RA.
In EPVB6D; decreased expression at the mRNA level; undetectable at the protein level in patient's fibroblasts.
Peroxisomal carnitine O-octanoyltransferase
In CMT2P; abolishes interaction with FUS.
In CMT2P; unknown pathological significance.
Rho guanine nucleotide exchange factor TIAM2
Calcium and integrin-binding family member 2
Found in a family with deafness carrying a likely pathogenic mutation in PDZD7; unknown pathological significance.
In DFNB48; decreases interaction with TMC1 and TMC2; no loss of localization to stereocilia; does not affect ATP-induced calcium release;.
In DFNB48; inhibits the ability to decrease ATP-induced calcium release; ; decreases interaction with TMC1 and TMC2; does not affect the localization in the cuticular plate or to the tip of stereocilia; does not affect binding with WHRN.
In DFNB48; inhibits the ability to decrease ATP-induced calcium release; decreases interaction with TMC1 and TMC2.
In DFNB48; stimulates the ability to decrease ATP-induced calcium release; decreases interaction with TMC1 and TMC2.
In DFNB48; unknown pathological significance.
In DFNB48; unknown pathological significance; decreases interaction with TMC1 and TMC2; no loss of localization to stereocilia; does not affect ATP-induced calcium release.
In USH1J and DFNB48; decreases interaction with TMC1 and TMC2.
Trinucleotide repeat-containing gene 18 protein
PiggyBac transposable element-derived protein 3
No arylsulfatase activity in the media of retinal epithelium cell.
Transmembrane and coiled-coil domain-containing protein 2
In CMD1CC; affects cardiac Z line integrity; no effect on protein expression and stability.
In CMD1CC; affects cardiac Z-disk integrity; no effect on protein expression and stability.
In CMH20; affects interaction with ACTA1 and F-actin.
In CMH20; the mutant protein accumulates in the cytoplasm but binding to ACTA1 is not altered.
No mitotic phosphorylation. No binding to spindle apparatus.
Still binds to the mitotic spindle but mitotic progression is impaired.
Zinc finger and BTB domain-containing protein 2
Sterile alpha motif domain-containing protein 10
Zinc finger Ran-binding domain-containing protein 2
Found in a patient with delayed psychomotor development, no speech and cataracts; no effect on binding to subunit PPP2CA; no effect on binding to subunit PPP2R1A.
In MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A.
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform
Abolished deubiquitinase activity; impaired ability to mediate deubiquitination of CGAS.
Abolished deubiquitinase activity; impaired ability to mediate deubiquitination of RIGI; when associated with A-380.
Abolished deubiquitinase activity; impaired ability to mediate deubiquitination of RIGI; when associated with S-87.
Ubiquitin carboxyl-terminal hydrolase 27
Signal-induced proliferation-associated protein 1
In MC4DN7; severely reduced COX6B1 protein levels in patient muscle.
Loss of ZDHHC5-catalyzed palmitoylation; when associated with S-20. Partial loss of ZDHHC5-catalyzed palmitoylation; when associated with S-19. Complete loss of palmitoylation; when associated with S-19 and S-20.
Loss of ZDHHC5-catalyzed palmitoylation; when associated with S-4. Partial loss of ZDHHC5-catalyzed palmitoylation; when associated with S-19. Complete loss of palmitoylation; when associated with S-4 and S-19.
Partial loss of ZDHHC5-catalyzed palmitoylation; when associated with S-4 or S-20. Complete loss of palmitoylation; when associated with S-4 and S-20.
Coiled-coil domain-containing protein 113
In MOCODB; in a patient with mild form of the disease; impairs interaction with MOCS2B.
Molybdopterin synthase catalytic subunit
Molybdopterin synthase sulfur carrier subunit
In KAND; affects subcellular location and motility; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; retains its ability to move processively along microtubules, but shows a strongly reduced velocity.
In KAND; affects subcellular location, binding to microtubules and motility; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; retains its ability to move processively along microtubules, but shows reduced velocity; may decrease interaction with microtubules.
In KAND; affects subcellular location; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells.
In KAND; affects subcellular location; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; complete loss of motility, when tested in vitro.
In KAND; affects subcellular location; strong decrease in localization at the distal tip of neurites and accumulation in the neuronal cell body, when assayed in differentiated SH-SY5Y cells.
In KAND; complete loss of motility, when tested in vitro.
In KAND; retains its ability to move processively along microtubules, but shows reduced velocity and processivity; decreased interaction with microtubules.
In KAND; strong decrease in localization at the distal tip of neurites and accumulation in the neuronal cell body, when assayed in differentiated SH-SY5Y cells.
In KAND; unknown pathological significance.
In NESCAVS; affects subcellular location, binding to microtubules and motility; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; retains its ability to move processively along microtubules, but shows reduced velocity and processivity; increased interaction with microtubules.
In NESCAVS; affects subcellular location, binding to microtubules and motility; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; retains its ability to move processively along microtubules, but shows reduced velocity; small decrease of interaction with microtubules.
In NESCAVS; affects subcellular location; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells.
In NESCAVS; affects subcellular location; reduced distal localization and increased accumulation throughout the cell body and proximal neurites; disrupts microtubule motility.
In NESCAVS; affects subcellular location; reduces accumulation in distal regions of the neurites.
In NESCAVS; disrupts microtubule motility.
In NESCAVS; reduces accumulation in distal regions of the neurites.
In NESCAVS; reduces accumulation in distal regions of the neurites; disrupts microtubule motility.
In NESCAVS; unknown pathological significance.
In SPG30; affects subcellular location, binding to microtubules and motility; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells; retains its ability to move processively along microtubules, but shows reduced velocity; small decrease of interaction with microtubules.
In SPG30; affects subcellular location; contrary to wild-type, does not accumulate in the distal tips of differentiated SH-SY5Y cells, but localizes closer to the cell body in transfected cells.
In SPG30; reduces accumulation in distal regions of the neurites.
In SPG30; reduces accumulation in distal regions of the neurites; no effect on microtubule motility.
In SPG30; unknown pathological significance.
Great reduction in ubiquitination. Complete loss of ubiquitination; when associated with 14-A--A-17.
Weak reduction in ubiquitination. Complete loss of ubiquitination; when associated with 53-A--A-56.
In AHC2 and DEE99; strong decrease in ATPase activity.
In AHC2; strong decrease in ATPase activity.
In DEE99; decreased affinity for sodium ions; decreased affinity for potassium ions.
In DEE99; decreased sodium/potassium-exchanging ATPase activity.
In DYT12; there is a drastic 40- to 50-fold reduction in Na(+) affinity in the mutant protein.
Probable disease-associated variant found in a patient with tonic-clonic seizures associated with profound developmental delay and paroxysmal movement disorder.
Sodium/potassium-transporting ATPase subunit alpha-3
Cytochrome c oxidase assembly protein COX11, mitochondrial
Reduces degradation of self-processed forms of TYSND1. Loss of ACOX1-processing.
10% reduced expression level compared to wild-type; transport properties comparable to wild-type.
20% reduced expression level compared to wild-type; significant lower activity in 6-mercaptopurine transport than wild-type.
40% reduced expression level compared to wild-type; higher transport of 9-(2-phosphonyl-methoxyethyl) adenine than wild-type.
ATP-binding cassette sub-family C member 4
Does not affect plasma membrane localization; 1.5 fold increase in PEG2 transport; does not affect estradiol 17-beta-D-glucuronide transport.
Does not affect plasma membrane localization; PEG2 transport is decreased by 50%; does not affect estradiol 17-beta-D-glucuronide transport.
Transport properties comparable to wild-type.
FYVE, RhoGEF and PH domain-containing protein 5
Mitochondrial pyruvate carrier 1-like protein
Tumor protein p53-inducible nuclear protein 1
2-(3-amino-3-carboxypropyl)histidine synthase subunit 1
In DEDSSH; impairs diphthamide modification of elongation factor 2.
In DEDSSH; normal diphthamide modification of elongation factor 2.
In breast and ovarian cancer; requires 2 nucleotide substitutions.
Loss of phosphorylation. Reduced binding of CHM and CHML binding.
Phosphomimetic mutant. Loss of CHM and CHML binding.
Microtubule-associated tumor suppressor 1
S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1
Transcription elongation factor A N-terminal and central domain-containing protein
Interferes with dimerization and reduces activity by 94%.
Decreases cytidine deaminase activity and antiviral activity.
Does not decrease cytidine deaminase activity.
Loss of cytidine deaminase activity and significant decrease in antiviral activity.
Loss of cytidine deaminase activity and significant decrease in antiviral activity; when associated with A-259.
Loss of cytidine deaminase activity and significant decrease in antiviral activity; when associated with A-67.
Loss of phosphorylation. No effect on cytidine deaminase activity or HIV-1 restriction activity.
Modifies the spectrum of action against mobile genetic elements; when associated with K-217.
Modifies the spectrum of action against mobile genetic elements; when associated with K-247.
No effect on cytidine deaminase and antiviral activity.
Phosphomimetic mutant which shows loss of cytidine deaminase activity and HIV-1 restriction activity.
Remains sensitive to HIV-1 Vif and able to bind Vif.
Resistant to HIV-1 Vif with complete loss of Vif-induced degradation and Vif binding.
Testis-specific serine/threonine-protein kinase 4
Abolishes ubiquitin binding and localization to nuclear foci after UV-induced DNA damage but does not affect catalytic activity.
Increased DNA polymerase activity and translesion bypass compared to wild-type.
Reduces DNA polymerase activity. Increases fidelity of replication and reduces translesion bypass.
Reduces binding to chromatin and to monoubiquitinated PCNA. Abolishes binding to monoubiquitinated PCNA; when associated with 705-E--H-713 Del.
Reduces cell resistance to UV-induced DNA damage.
Reduces cell resistance to UV-induced DNA damage. Reduces binding to chromatin and to monoubiquitinated PCNA. Abolishes binding to monoubiquitinated PCNA; when associated with 324-A--A-326.
Reduces enzymatic activity by two-thirds.
Severe reduction in thymine dimer translesion bypass.
Loss of histone methyltransferase activity.
Reduced histone methyltransferase activity.
Reduced phosphorylation. Phosphorylation is almost abolished; when associated with A-191.
Strongly reduced phosphorylation. Phosphorylation is almost abolished; when associated with A-182.
Transcription elongation factor 1 homolog
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A
In CDG1W; affects activity resulting in hypoglycosylation of STT3A-specific substrates.
In CDG1WAD; partial loss of function, when tested in a heterologous system; does not affect expression levels.
In CDG1WAD; unknown pathological significance; partial loss of function, when tested in a heterologous system.
In CDG1WAD; unknown pathological significance; partial loss of function, when tested in a heterologous system; does not affect expression levels.
DNA-directed RNA polymerase III subunit RPC5
Complete loss of CDC42 binding and CDC42-mediated autophosphorylation.
Significant phosphorylation reduction; when associated with F-72; F-84 and F-178.
Significant phosphorylation reduction; when associated with F-72; F-84 and F-96.
Significant phosphorylation reduction; when associated with F-72; F-96 and F-178.
Significant phosphorylation reduction; when associated with F-84; F-96 and F-178.
Found in a patient with Leber congenital amaurosis; unknown pathological significance.
Found in patients with retinitis pigmentosa; unknown pathological significance.
In DFNA11; disturb calmodulin/MYO7A binding.
In USH1B; is predicted to alter the normal splicing of exon 6.
In USH1B; unknown pathological significance.
Abolishes expression at cell surface and glucagon binding.
Abolishes glucagon binding. Strongly reduces expression at the cell surface.
Causes the formation of an artifactual disulfide bond that abolishes glucagon binding; when associated with C-113.
Causes the formation of an artifactual disulfide bond that abolishes glucagon binding; when associated with C-209.
Causes the formation of an artifactual disulfide bond that interferes with glucagon binding; when associated with C-130.
Causes the formation of an artifactual disulfide bond that interferes with glucagon binding; when associated with C-210.
In MVAH; loss of glucagon-elicited cAMP production; no effect on localization to the cell membrane.
In MVAH; when associated in cis with H-225; decreased glucagon binding and decreased glucagon-elicited cAMP production; no effect on localization to the cell membrane.
In MVAH; when associated in cis with M-368; decreased glucagon binding and decreased glucagon-elicited cAMP production; decreased localization to the cell membrane.
No effect on glucagon-elicited cAMP production.
Strongly decreases affinity for synthetic antagonist.
Strongly reduced affinity for glucagon. Increased constitutive signaling via G-proteins.
Impairs CDK2 T-160 phosphorylation and activity.
Found in patients with gastrointestinal diffuse large cell lymphoma; impairs inhibitory activity on CARD11-induced NF-kappa-B activation.
Found in patients with gastrointestinal diffuse large cell lymphoma; somatic mutation; impairs inhibitory activity on CARD11-induced NF-kappa-B activation and impairs interaction with TNFAIP3.
Reduces phosphorylation; reduces CHUK-mediated NF-kappa-B activation.
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7
AP-1 complex-associated regulatory protein
Decreases interaction with AP1G1; when associated with L-260.
Decreases interaction with AP1G1; when associated with L-264.
Loss of association with membranes, no effect on interaction with AP1G1; when associated with 4-S-S-5.
Loss of association with membranes, no effect on interaction with AP1G1; when associated with 9-S.
Loss of association with the Arp2/3 complex and endosomal colocalization. Abolishes interaction with KLC2, no effect on interaction with AP1G1.
Found in patients with non-obstructive azoospermia; unknown pathological significance.
Found in patients with non-obstructive azoospermia; unknown pathological significance; decreased expression of MAP1LC3B; increased programmed cell death in spermatogenic cells.
In isoform 10, isoform 11 and isoform 14.
In isoform 2, isoform 3, isoform 4, isoform 6, isoform 9, isoform 11, isoform 13 and isoform 14.
In isoform 5, isoform 6, isoform 7, isoform 8 and isoform 13.
In isoform 6, isoform 9, isoform 10, isoform 11 and isoform 12.
In isoform 7, isoform 8, isoform 13 and isoform 14.
In isoform 8, isoform 10 and isoform 12.
Loss of cell membrane localization. Significant reduction in transport activity.
Loss of cell membrane localization. Unable to rescue phagocyte deficient acidification phenotype of SLC4A7 knockout.
Loss of interaction with CA2. Loss of regulation by CA2.
No effect on cell membrane localization. Unable to rescue phagocyte deficient acidification phenotype of SLC4A7 knockout.
No effect on interaction with CA2. No effect on regulation by CA2.
Isochorismatase domain-containing protein 2
Important loss of interaction with YAP1 and complete loss of transforming ability.
Loss of interaction with YAP1 and also activation by YAP1.
Zinc finger protein with KRAB and SCAN domains 4
Pregnancy-specific beta-1-glycoprotein 6
Decreased enzyme activity with arachidonic acid. Loss of cyclooxygenase activity; when associated with V-519.
Decreased protein stability. Increased decrease of protein stability; when associated with A-516.
Does not affect activation by nitric oxid (NO).
Impairs two-electron hydroperoxide reduction and cyclooxygenase activity.
Impairs two-electron hydroperoxide reduction.
Increases two-electron hydroperoxide reduction. Has no effect on cyclooxygenase activity.
Loss of cyclooxygenase activity. Loss of cyclooxygenase activity; when associated with T-516.
No effect on protein stability. Increased decrease of protein stability; when associated with A-371.
Prevents activation by nitric oxid (NO).
Reduces two-electron hydroperoxide reduction and cyclooxygenase activity. Catalyzes predominantly one-electron hydroperoxide reduction.
X-linked interleukin-1 receptor accessory protein-like 2
Does not abolish monoubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex, revealing flexibility of ubiquitination sites; when associated with R-1217.
Does not abolish monoubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex, revealing flexibility of ubiquitination sites; when associated with R-647.
In isoform 2, isoform 7, isoform 9 and isoform 10.
In isoform 4, isoform 6, isoform 7 and isoform 10.
Secreted Ly-6/uPAR domain-containing protein 2
Proprotein convertase subtilisin/kexin type 7
Testis-specific chromodomain protein Y 1
Abolishes histone acetyltransferase activity.
Found in a severe neurodevelopmental disorder similar to Li-Ghorbani-Weisz-Hubshman syndrome with apparently autosomal recessive inheritance; unknown pathological significance; loss of protein expression.
Found in a severe neurodevelopmental disorder similar to Li-Ghorbani-Weisz-Hubshman syndrome with apparently autosomal recessive inheritance; unknown pathological significance; no effect on protein expression; no effect on localization to the nucleus; no effect on MSL complex assembly; decreased histone acetyltransferase activity.
In LIGOWS; no effect on protein expression; no effect on MSL complex assembly; decreased histone acetyltransferase activity.
In LIGOWS; unknown pathological significance; no effect on protein expression; no effect on MSL complex assembly; decreased histone acetyltransferase activity.
Strongly reduces histone acetyltransferase activity.
In AD; associated with susceptibility to late-onset disease; increased susceptibility to neuronal cell death.
In HLD10; mild decrease of homodimerization; does not affect mitochondrial localization.
In HLD10; severe decrease of protein amount; does not affect mitochondrial localization.
Telomerase RNA component interacting RNase
Guanylate cyclase C-activating peptide 2
Bone morphogenetic protein receptor type-2
In PPH1; abnormal subcellular localization; significant increase in apoptosis of endothelial cells; significant decrease in proliferation of endothelial cells; significant decrease in nitric oxide synthesis by endothelial cells; significant increase in endothelin 1 synthesis by endothelial cells.
In PPH1; alters alternative splicing of BMPR2.
In PPH1; changed localization to the plasma membrane.
In PPH1; leads to constitutive activation of the MAPK14 pathway.
In PPH1; loss of localization to the plasma membrane; localized to the cytoplasm.
In PPH1; significant decrease in nitric oxide synthesis by endothelial cells.
In PPH1; unknown pathological significance; unchanged subcellular localization.
Decreases affinity for UAF2 by 3 orders of magnitude.
In MDS; somatic mutation; affects alternative splicing of target sequences resulting in increased splicing efficiency, exon skipping and alternative splice site utilization; no effect on localization to nuclear speckles.
In MDS; somatic mutation; affects alternative splicing of target sequences.
NACHT and WD repeat domain-containing protein 2
RING finger and transmembrane domain-containing protein 2
Decreases glycosylation levels. Decreases thiamine pyrophosphate uptake.
Decreases glycosylation levels. No effect on thiamine pyrophosphate uptake.
In DFNA72; decreases choline transmembrane transporter activity.
No effect on thiamine pyrophosphate transporter activity.
Diffuse cytoplasmic distribution and loss of localization to lysosomes. No effect on acetylation.
Loss of GTP/GDP-binding. Affects chromosome segregation.
No effect on localization and acetylation.
Preferentially binds GDP. Alters chromosome segregation. Decreases interaction with VPS41. Loss of lysosomal location. Loss of interaction with PLEKHM1.
Prevents GTP hydrolysis. No effect on lysosomal location. Alters lysosomes cellular distribution and motility. Increases interaction with VPS41. No effect on interaction with PLEKHM1.
Decreased accumulation to the double-strand break (DSB) sites.
Decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.
Found in patient with atrial fibrillation.
Found in patients with atrial fibrillation; unknown pathological significance.
Found in patients with lipodystrophy; no effect on nuclear lamin A localization; no effect on the interaction with SYNE2.
Found in patients with skeletal and cardiac muscular dystrophies; no effect on nuclear lamin A localization; no effect on the interaction with SYNE2.
Found in patients with skeletal and cardiac muscular dystrophies; unknown pathological significance; no effect on nuclear lamin A localization; no effect on the interaction with SYNE2.
In CMD1A and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In CMD1A; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci.
In CMD1A; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.
In CMD1A; dramatically aberrant localization with almost no nuclear rim staining and formation of intranuclear foci.
In CMD1A; dramatically aberrant localization with almost no nuclear rim staining and increased formation of intranuclear foci.
In CMD1A; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In CMD1A; dramatically increases the size of intranuclear speckles and reduces their number; this phenotype is only partially reversed by coexpression of the G-192 mutation and wild-type lamin-C; precludes insertion of lamin-C into the nuclear envelope when co-transfected with the G-192 LMNA; G-192 lamin-C expression totally disrupts the SUMO1 pattern.
In CMD1A; grossly abnormal nuclear shape with the nuclear envelope producing prominent lobules in about 10% of cultured skin fibroblasts from heterozygous patients.
In CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In CMD1A; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreased sumoylation; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; associated with increased cell death.
In CMD1A; no effect on nuclear morphology and lamin A localization.
In CMD1A; no effect on nuclear morphology but restricts lamin A to the cytoplasm.
In CMD1A; unknown pathological significance.
In CMDHH; phenotype originally designated as atypical Werner syndrome.
In EDMD2 and CMD1A; aberrant localization with decreased nuclear rim staining and increased formation of intranuclear foci.
In EDMD2 and CMD1A; modest and non-specific nuclear membrane alterations; the phenotype is entirely reversed by coexpression of the S-541 mutation and wild-type lamin-C.
In EDMD2 and FPLD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; abnormal nuclear localization; forms nuclear foci in about 13% of cultured skin fibroblasts from heterozygous patients; no effect on protein level.
In EDMD2 and MDCL; aberrant localization with decreased nuclear rim staining and formation of intranuclear foci when transfected in C2C12 myoblasts; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; interacts with itself and with wild-type LMNA and LMNB1; no effect on protein level.
In EDMD2; abnormal nuclear localization in a honeycomb expression pattern in about 11% of cultured skin fibroblasts from heterozygous patients; no effect on protein level.
In EDMD2; abnormal nuclear localization in a honeycomb expression pattern in about 22% of cultured skin fibroblasts from heterozygous patients; enhances the interaction with SYNE2; no effect on nuclear localization; no effect on protein level.
In EDMD2; abnormal nuclear localization; forms nuclear foci in about 8% of cultured skin fibroblasts from heterozygous patients; interacts with itself and with wild-type LMNA and LMNB1; no effect on protein level.
In EDMD2; dramatically aberrant localization with decreased nuclear rim staining and formation of intranuclear foci; distribution of endogenous LMNA, LMNB1 and LMNB2 are altered in cells expressing this mutant; causes an increased loss of endogenous EMD from the nuclear envelope; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In EDMD2; found also in a patient with limb-girdle muscular dystrophy; sporadic.
In EDMD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In EDMD2; interacts with itself and with wild-type LMNA and LMNB1; reduced binding to SUN1; no decrease in the stability compared with wild-type.
In EDMD2; mis-localized in the nucleus; causes nuclear deformations and LMNB1 redistribution.
In EDMD2; mis-localized in the nucleus; does not alter nuclear size or shape.
In EDMD2; mislocalized in the nucleus; does not alter nuclear size or shape.
In EDMD2; no effect on protein level; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients.
In EDMD2; no obvious effect on nuclear morphology in cultured skin fibroblasts from heterozygous patients; no effect on protein level.
In FPLD2 and CMD1A; no effect on nuclear morphology and lamin A localization.
In FPLD2; abnormal nuclear localization in a honeycomb expression pattern in about 10% of cultured skin fibroblasts from heterozygous patients; no effect on protein level.
In FPLD2; increase in nuclear blebbing and formation of honeycomb-like structures in the nuclei with no accumulation of prelamin A in skin fibroblasts; causes oligomerization of the C-terminal globular domain of lamins A and C under no-reducing conditions and increases binding affinity for DNA; increases sensitivity to oxidative stress; no significant differences in stability and structure compared with the wild-type.
In FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type.
In FPLD2; interacts with itself and with wild-type LMNA and LMNB1; no decrease in the stability compared with wild-type; decreases binding affinity for DNA; increases sensitivity to oxidative stress.
In HGPS and EDMD2; unknown pathological significance; partially inhibits tail cleavage.
In HGPS; atypical form with late onset; abnormal nuclear morphology with single or multple blebs, lobulation and occasional ringed or donut shaped nuclei.
In HGPS; might be associated with early and severe strokes.
In HGPS; phenotype originally designated as atypical Werner syndrome.
In HGPS; reduced binding to SUN1; may affect splicing by activating a cryptic splice donor site.
In MDCL and EDMD2; mislocalized in the nucleus; causes nuclear deformations and LMNB1 redistribution.
In an atypical progeroid patient; diagnosed as Seip syndrome; unknown pathological significance.
In an atypical progeroid patient; diagnosed as Werner syndrome.
Increased accumulation to the double-strand break (DSB) sites.
Loss of interaction with NARF. Abolishes farnesylation.
Probable disease-associated variant found in a patient with metabolic syndrome.
Probable disease-associated variant found in patient with severe metabolic syndrome; no effect on nuclear lamin A localization; no effect on the interaction with SYNE2.
Probable disease-associated variant found in patients with metabolic syndromes; no effect on nuclear lamin A localization; no effect on the interaction with SYNE2.
Rare variant; found in patients with atrial fibrillation; unknown pathological significance; no effect on nuclear lamin A localization; enhances the interaction with SYNE2; causes nuclear deformations in heat shock experiments.
Removed in Prelamin-A/C form and in Lamin-A/C form
Eukaryotic translation initiation factor 3 subunit C
Zinc fingers and homeoboxes protein 1, isoform 2
UDP-N-acetylglucosamine/UDP-glucose/GDP-mannose transporter
Abolishes interaction with SMAD2 and SMAD7.
Increases auto-ubiquitination; when associated with A-56.
Increases auto-ubiquitination; when associated with A-57.
Loss of activity. Loss of ability to ubiquitinate SMAD1 and SMAD2 and no down-regulation of SMAD1 and SMAD2 protein levels.
Loss of catalytic activity. Increases SMAD7-bound TGF-beta receptors in membrane rafts. Decreases interaction with TTC3. Decreased VP40 virus-like particle budding.
Found in a subject suffering from insomnia; functional analysis reveals a slower rate of the fast phase of desensitization compared with alpha1beta3gamma2S GABA(A) receptors; current deactivation is faster in the mutated receptors.
Found in patients with Dravet syndrome; unknown pathological significance.
Gamma-aminobutyric acid receptor subunit beta-3
In DEE43; no effect on localization to the plasma membrane; decreased GABA-gated chloride ion channel activity; decreased single channel open probability.
In DEE43; unknown pathological significance.
In ECA5, the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.
In ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.
Associated with elevated mean fasting plasma glucose level.
EF-hand and coiled-coil domain-containing protein 1
Thyroid hormone-inducible hepatic protein
5'-AMP-activated protein kinase subunit beta-1
Abolishes myristoylation and AMP-enhanced phosphorylation of PRKAA1 or PRKAA2.
ATP-binding cassette sub-family G member 1
Affects ATP binding. Does not affect efflux of 7beta-hydroxycholesterol. Does not affect localization at plasma membrane. Does not affect homodimerization. Decreases cholesterol and phospholipids efflux. Does not affect heretodimerization with ABCG4.
Does not affect ABCG1-mediated cholesterol efflux; when associated with I-498.
Does not affect ABCG1-mediated cholesterol efflux; when associated with I-499.
Dramatically reduces the ability of ABCG1 to mediate cholesterol efflux; when associated with I-498.
Dramatically reduces the ability of ABCG1 to mediate cholesterol efflux; when associated with I-499.
Significantly decreases ABCG1-mediated cholesterol efflux.
Significantly reduces interaction with CAV1; when associated with A-491. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-491.
Significantly reduces interaction with CAV1; when associated with A-493. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-493.
Significantly reduces interaction with CAV1; when associated with A-498. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-498. Affects subcellular location at plasma membrane; when associated with A-498. Affects ABCG1 traffincking to the plasma membrane; when associated with A-498.
Significantly reduces interaction with CAV1; when associated with A-499. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-499. Affects subcellular location at plasma membrane; when associated with A-499. Affects ABCG1 traffincking to the plasma membrane; when associated with A-499.
Inhibits glycosylation and does not inhibit RHBDL4/RHBDD1-induced cleavage; when associated with A-256.
Inhibits glycosylation and does not inhibit RHBDL4/RHBDD1-induced cleavage; when associated with A-344.
Strongly inhibits RHBDL4/RHBDD1-induced cleavage.
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase-like protein MGAT4D
Centriolar satellite-associated tubulin polyglutamylase complex regulator 1
Pituitary adenylate cyclase-activating polypeptide 27
Pituitary adenylate cyclase-activating polypeptide 38
Strongly reduced affinity for ADCYAP1R1.
NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
Abolishes enzymatic activity. Loss of the pro-apoptotic function.
Ubiquitin carboxyl-terminal hydrolase 17-like protein 24
Reduced binding to myristoylated proteins; when associated with A-144 and A-148.
Reduced binding to myristoylated proteins; when associated with A-144 and A-207.
Reduced binding to myristoylated proteins; when associated with A-148 and A-207.
Loss of interaction with CCM2 and PXN; when associated with D-132; D-139 and D-172.
Loss of interaction with CCM2 and PXN; when associated with D-132; D-139 and D-179.
Loss of interaction with CCM2 and PXN; when associated with D-132; D-172 and D-179.
Loss of interaction with CCM2 and PXN; when associated with D-139; D-172 and D-179.
Significantly decreased carbohydrate binding.
Complete loss of cleavage by CV3B; when associated with A-653; A-659 and A-671.
Complete loss of cleavage by CV3B; when associated with A-653; A-659 and A-702.
Complete loss of cleavage by CV3B; when associated with A-653; A-671 and A-702.
Complete loss of cleavage by CV3B; when associated with A-659; A-671 and A-702.
Complete loss of cleavage by HCV NS3/4A protease.
Loss of TCAM1-induced NF-kappa-B activation. Reduces interaction with TRAF6 and activation of NF-kappa-B signaling pathway; when associated with A-88 and A-303.
Loss of TCAM1-induced NF-kappa-B and IRF3 activation.
Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-252 and A-303.
Reduces binding to TRAF6 and activation of NFKB signaling pathway; when associated with A-88 and A-252.
Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-281.
Resistant to caspase cleavage, no effect on TRIM38-mediated degradation; when associated with E-289.
TIR domain-containing adapter molecule 1
PWWP domain-containing DNA repair factor 3A
Loss of interaction with CUL1, CUL2, CUL3, CUL4A, CUL5, CAND1 and RBX1; when associated with A-195 and R-219. Does not affect localization at nucleus; when associated with A-195 and R-219.
Loss of interaction with CUL1, CUL2, CUL3, CUL4A, CUL5, CAND1 and RBX1; when associated with R-219 and A-225. Does not affect localization at nucleus; when associated with R-219 and A-225.
Loss of interaction with RBX1, CUL1 and CAND1.
Loss of interaction with RBX1, CUL1 and CAND1. Loss of interaction with CUL1, CUL2, CUL3, CUL4A, CUL5, CAND1 and RBX1; when associated with A-195 and A-225. Does not affect localization at nucleus; when associated with A-195 and A-225.
Loss of interaction with RBX1, CUL1, CUL2, CUL3 and CAND1. Does not affect interaction with UBE2M and NEDD8. Fails to augment Cul3 neddylation beyond basal levels.
Impairs protein folding and stability. Strongly reduced cell surface expression.
No effect on agonist binding. Strongly increases dissociation of bound lysergic acid diethylamine, without affecting binding affinity. Reduces signaling via arrestins, but has no effect on signaling via the phosphatidylinositol-calcium second messenger system.
[DE]RFG motif; may stabilize a conformation that preferentially activates signaling via beta-arrestin family members
Abolishes sensitivity to N-ethymaleimide. Severely decreases phenylalanine transport activity. Decreases affinity for phenylalanine. Strongly decreases glycosylation. Strongly decreases expression. Reduces membrane localization.
Increases affinity for phenylalanine. Increases phenylalanine transport activity. Strongly decreases glycosylation. Strongly decreases expression. Increases membrane localization.
Large neutral amino acids transporter small subunit 4
Slightly decreases phenylalanine transport.
Slightly decreases phenylalanine transport. Does not affect membrane localization.
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
In CSNB1H; sporadic case; unknown pathological significance.
WAP four-disulfide core domain protein 1
Schiff-base intermediate with substrate; via topaquinone
In IDDRP; unknown pathological significance.
No effect on CCNA2/CDK2 complex-binding.
S phase cyclin A-associated protein in the endoplasmic reticulum
Chromodomain-helicase-DNA-binding protein 8
In AUTS18; unknown pathological significance.
Abolishes signaling via G-proteins. Abolishes antagonist binding.
Gamma-aminobutyric acid type B receptor subunit 1
Slightly decreases signaling via G-proteins.
Strongly reduces signaling via G-proteins. Abolishes antagonist binding.
Strongly reduces signaling via G-proteins. No effect on antagonist binding.
Strongly reduces signaling via G-proteins. Strongly reduces antagonist binding.
Decreased histone methyltransferase activity.
Enhances methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1.
Found in a patient with B-cell lymphoma; increased hypertrimethylation of H3K27; changed substrate preferences; confers biochemical activity independent of H3K27 methylation state.
Found in a patient with chronic myelomonocytic leukemia; somatic mutation; loss of histone methyltransferase activity.
Found in a patient with follicular lymphoma; also in diffuse large B-cell lymphoma; somatic mutation; changed substrate preferences; prefers substrates with greater methylation H3K27me0<me1<me2.
Found in a patient with myelodysplastic syndrome and myelodysplastic-myeloproliferative neoplasms; somatic mutation; loss of histone methyltransferase activity.
Found in a patient with myeloid disorders; somatic mutation; loss of histone methyltransferase activity.
Found in patients with follicular lymphoma; also in diffuse large B-cell lymphoma; somatic mutation.
Found in patients with follicular lymphoma; also in diffuse large B-cell lymphoma; somatic mutation; changed substrate preferences; prefers substrates with greater methylation H3K27me0<me1<me2.
Impaired CDK1- and CDK-2 mediated phosphorylation and subsequent gene silencing. Altered EZH2-mediated cell proliferation and migration.
In WVS; decreased histone methyltransferase activity.
In WVS; unknown pathological significance.
In a patient with chronic myelomonocytic leukemia.
In a patient with diffuse large B-cell lymphoma; somatic mutation; changed substrate preferences; prefers substrates with greater methylation H3K27me0<me1<me2.
Reduces methyltransferase activity towards 'Lys-27' of histone H3 and abrogates phosphorylation by PKB/AKT1.
Strongly decreases histone methyltransferase activity.
Strongly impairs methyltransferase activity towards 'Lys-27' of histone H3.
Zinc finger and SCAN domain-containing protein 26
Uncharacterized protein C15orf62, mitochondrial
In HYRPRO1 and SCZD4; associated with disease susceptibility; mild decrease of enzymatic activity.
In HYRPRO1 and SCZD4; may be associated with disease susceptibility; enhanced enzymatic activity.
In HYRPRO1 and SCZD4; may be associated with disease susceptibility; moderate reduction of enzymatic activity.
In HYRPRO1 and SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity.
In HYRPRO1; mild decrease of enzymatic activity.
In HYRPRO1; moderate reduction of enzymatic activity.
In SCZD4; may be associated with disease susceptibility; strongly reduced affinity for FAD; strongly reduced enzymatic activity.
In SCZD4; may be associated with disease susceptibility; strongly reduced enzymatic activity.
May be a risk factor for schizophrenia; moderate reduction of enzymatic activity.
Moderate reduction of enzymatic activity.
Associated with mild anemia and a tendency to iron loading.
Complete loss of HAMP-dependent ubiquitination.
No loss of ubiquitination; when associated with R-236.
No loss of ubiquitination; when associated with R-253.
Inactive sodium-dependent neutral amino acid transporter B(0)AT3
Common variant associated with low mean resting heart rate; associated with decreased mortality risk in patients with congestive heart failure.
Loss of interaction with GOPC. Loss of interaction with RAPGEF2. Abolishes agonist-induced Ras activation.
Loss of interaction with GOPC; when associated with A-477.
Loss of interaction with RAPGEF2. Abolishes agonist-induced Ras activation.
Rare variant associated with short sleep; results in decreased adenylate cyclase-activating adrenergic receptor signaling; decreased protein stability.
In BRYLIB1 and BRYLIB2; unknown pathological significance.
In BRYLIB1; decreased protein abundance.
In BRYLIB1; unknown pathological significance.
In BRYLIB1; unknown pathological significance; decreased protein abundance; increased interaction with DAXX; not changed subcellular location.
In BRYLIB1; unknown pathological significance; increased protein abundance.
In BRYLIB1; unknown pathological significance; no effect on protein abundance.
In BRYLIB2; unknown pathological significance.
In BRYLIB2; unknown pathological significance; decreased protein abundance.
In BRYLIB2; unknown pathological significance; no effect on protein abundance.
In GLM and BRYLIB2; glioblastoma multiforme samples; somatic mutation; affects regulation of gene expression and results in up-regulation of MYCN; results in global decrease of H3K36me2 and H3K36me3 levels; has no effect on H3K27me3 levels.
In GLM; glioblastoma multiforme samples and diffuse intrinsic pontine glioma; somatic mutation; more prevalent in pediatric than adult malignancies; results in reduced allosteric activation of PRC2 causing a global decrease of H3K27me3 levels; has no effect on H3K4me3 or H3K36me3 levels.
In GLM; glioblastoma multiforme samples; somatic mutation; also found in osteosarcoma samples; results in global decrease of H3K36me2 and H3K36me3 levels; has no effect on H3K27me3 levels.
Loss of interaction with DNAJC9, but not with other histone chaperones, such as ASF1A, MCCM2, NASP or SPT2.
Probable disease-associated variant found in chondroblastoma and clear cell chondrosarcoma; somatic mutation; also found in a subset of human papillomavirus-negative head and neck squamous cell carcinomas; results in global decrease of H3K36me2 and H3K36me3 levels and increased H3K27me3 levels.
Probable disease-associated variant found in giant cell tumors of bone; somatic mutation.
Reduced binding of histone H1 to histone H3.3-containing nucleosomes.
Found in a patient with a variant form of Marfan syndrome; unknown pathological significance.
Found in a patient with mild osteogenesis imperfecta associated with increased bone mineral density; results in defective type I procollagen processing; incorporation of the immature procollagen into the matrix leads to increased bone matrix mineralization and altered collagen fibril structure.
In OI2; requires 2 nucleotide substitutions.
In OIEDS2; decreased N-terminal propeptide processing.
In patients with sporadic hearing loss; no detectable proteolytic activity in a yeast-based protease assay.
Reduced proteolytic activity in a yeast-based protease assay.
Associated with low LDL-C content and protection against coronary heart disease.
Found in a non-responder to ezetimibe treatment.
NPC1-like intracellular cholesterol transporter 1
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3
In IBD31; decreased stability; increased degradation; decreased localization to the nucleus; decreased localization to the extracellular space; decreased function in regulation of inflammatory response.
Abolishes E3 ubiquitin-protein ligase activity.
RING finger and CHY zinc finger domain-containing protein 1
U6 snRNA-associated Sm-like protein LSm1
Cell division cycle 7-related protein kinase
FYVE, RhoGEF and PH domain-containing protein 4
In CMT4H; found in patient's fibroblasts but absent from peripheral nerve where splicing defects and aberrant transcripts are detected.
Found in a family with foveal hypoplasia; unknown pathological significance.
Abolished interaction with histone H4 and recruitment to replication forks without affecting interaction with MMS22L.
In SEMDSP; decreased function in double-strand break repair via homologous recombination.
In SEMDSP; decreased function in double-strand break repair via homologous recombination; decreased protein amount in patient cells.
In SEMDSP; disease phenotype includes immunologic and hematologic abnormalities.
In SEMDSP; disease phenotype includes immunologic and hematologic abnormalities; unknown pathological significance.
In SEMDSP; disease phenotype includes primary aphakia and absent pupils.
In SEMDSP; unknown pathological significance.
In SEMDSP; unknown pathological significance; decreased function in double-strand break repair via homologous recombination.
In SEMDSP; unknown pathological significance; genomic instability; when associated with R-1090.
In SEMDSP; unknown pathological significance; genomic instability; when associated with R-430.
Ankyrin repeat and IBR domain-containing protein 1
Does not prevent the targeting of the protein to lysosomes completely.
May act as a modifier of Gaucher disease.
Normal targeting of the protein to lysosomes.
Prevents the targeting of the protein to lysosomes.
Some loss in the efficiency of targeting of the protein to lysosomes.
Negative regulator of P-body association
In NEDSGA; unknown pathological significance.
Abolished binding to N6-methyladenosine (m6A)-containing RNAs.
Abolishes RNA-binding and ability to influence alternative splice site selection.
Abolishes binding to N6-methyladenosine (m6A)-containing RNAs. Abolishes binding to m6A-containing mRNAs; when associated with A-377.
Abolishes binding to N6-methyladenosine (m6A)-containing RNAs. Abolishes binding to m6A-containing mRNAs; when associated with A-428.
Does not affect ability to influence alternative splice site selection.
Reduced binding affinity for N6-methyladenosine (m6A)-containing RNAs by 100-fold.
Reduced binding affinity for N6-methyladenosine (m6A)-containing RNAs by 9-fold.
Reduced binding to N6-methyladenosine (m6A)-containing RNAs.
Putative uncharacterized protein C5orf58
Membrane-spanning 4-domains subfamily A member 8
50% reduction in TAF1-binding, reduced incorporation of TAF7 into TFIID complexes.
Reduced H3 acetylation and transcription at target promoters.
Transcription initiation factor TFIID subunit 7
Tumor necrosis factor ligand superfamily member 14, membrane form
Tumor necrosis factor ligand superfamily member 14, soluble form
Abolishes 'Lys-63'-linked polyubiquitination.
Loss of phosphorylation site. Abolishes activation of NF-kappa-B.
Reduces global phosphorylation. Partial reduction of TNF-dependent activation of NF-kappa-B and activation of JNK.
Slight increase of TNF-dependent activation of NF-kappa-B and activation of JNK.
Strongly reduced interaction with BIRC3.
Abolishes ceramide and phosphatidylcholine binding. Decreases apoptosis frequency following mitochondrial targeting of ceramide.
Voltage-dependent anion-selective channel protein 2
High mobility group nucleosome-binding domain-containing protein 3
Associated with susceptibility to obesity; completely lacks signaling in response to agonist stimulation; coexpression of the wild-type and the mutant receptor shows that it does not exert dominant-negative activity on wild-type.
Associated with susceptibility to obesity; in vitro expression studies demonstrate that the mutation causes complete loss of function; transfected cells show diffuse cytoplasmic staining indicating intracellular retention of the receptor.
Have ligand binding and signaling properties similar to wild-type.
Alters endoplasmic reticulum morphogenesis.
Alters endoplasmic reticulum morphology.
Affects voltage-dependent inhibition by dihydropyridines; when associated with F-954.
Affects voltage-dependent inhibition by dihydropyridines; when associated with I-958.
In BRGDA3; unknown pathological significance; affects channel activity.
In LQT8; gain-of-function effect on channel activity.
In LQT8; gain-of-function effect on channel activity; slower inactivation.
In LQT8; leads to increased calcium currents; increased surface membrane expression of the channel.
In LQT8; unknown pathological significance.
In LQT8; unknown pathological significance; increased channel activity.
In LQT8; unknown pathological significance; no effect on channel activity.
In TS and LQT8; electrophysiological phenotype characterized by loss of current density and gain-of-function shift in activation leading to increased steady-state current; gain of function activity.
In TS; causes a nearly complete loss of voltage-dependent channel inactivation.
In TS; only with cardiac manifestation; decreased current density; associated with slower inactivation.
In TS; only with cardiac manifestation; decreased current density; associated with slower inactivation; altered localization.
In isoform 10, isoform 13, isoform 14, isoform 15, isoform 24, isoform 25, isoform 27 and isoform 29.
In isoform 11, isoform 12, isoform 13, isoform 14, isoform 15, isoform 17, isoform 19, isoform 20, isoform 21, isoform 22, isoform 23, isoform 24, isoform 25, isoform 26, isoform 27, isoform 29, isoform 30, isoform 31, isoform 32, isoform 35 and isoform 37.
In isoform 16, isoform 17, isoform 18 and isoform 28.
In isoform 2, isoform 18 and isoform 28.
In isoform 3, isoform 16, isoform 17, isoform 18, isoform 23, isoform 28, isoform 36 and isoform 37.
In isoform 4, isoform 19, isoform 20, isoform 21, isoform 23, isoform 26, isoform 27, isoform 29, isoform 32 and isoform 33.
In isoform 5, isoform 12, isoform 13, isoform 14, isoform 15, isoform 16, isoform 17, isoform 18, isoform 22, isoform 24, isoform 25, isoform 28, isoform 31, isoform 35, isoform 36 and isoform 37.
In isoform 6, isoform 12, isoform 14, isoform 15, isoform 19, isoform 20, isoform 23, isoform 24, isoform 25, isoform 26, isoform 27, isoform 28, isoform 29, isoform 30 and isoform 33.
In isoform 7, isoform 13, isoform 16, isoform 17, isoform 18, isoform 21, isoform 22, isoform 35, isoform 36 and isoform 37.
In isoform 8, isoform 19, isoform 25, isoform 28, isoform 29 and isoform 32.
Loss of a low-affinity interaction with CALM1. No effect on channel inactivation by Ca(2+) and calmodulin.
Loss of channel inactivation by Ca(2+) and calmodulin; when associated with 1666-A--A-1670.
Loss of selectivity for divalent over monovalent cations.
Mildly decreased channel activity. No effect on channel inactivation. Loss of channel inactivation by Ca(2+) and calmodulin; when associated with A-1672.
Rare variant; found in a case of sudden unexplained death in the young; unknown pathological significance; results in increased whole-cell calcium currents.
Rare variant; found in a case of sudden unexplained death in the young; unknown pathological significance; results in reduced whole-cell calcium currents.
Voltage-dependent L-type calcium channel subunit alpha-1C
In MRD1; unknown pathological significance.
Abolished poly(ADP-ribose) glycohydrolase activity.
Abolishes nuclear targeting; when associated with A-12.
Abolishes nuclear targeting; when associated with G-13.
Reduced poly(ADP-ribose) glycohydrolase activity.
No effect on palmitoleoylation and secretion; the threonine can functionally replace the serine.
No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a, exhibits dominant negative properties; when associated with A-334.
No signaling activity despite the presence of significant amounts of secreted monomeric Wnt3a, exhibits dominant negative properties; when associated with A-335.
Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-298.
Strongly reduced ability to stimulate Wnt-responsive reporters; when associated with Q-87.
Loss of protein-cysteine S-palmitoyltransferase activity.
Non-canonical dileucine endocytic signal
In a patient with retinal dytrophy; unknown pathological significance; loss of interaction with BSG; loss of ability to sustain retinal cone survival.
Diacylglycerol O-acyltransferase 2-like protein 6
Abolished protein-L-histidine N-pros-methyltransferase activity.
Protein-L-histidine N-pros-methyltransferase
Ankyrin repeat domain-containing protein 54
Abolishes ability to demethylate N(6)-methyladenosine RNAs (m6A) RNAs.
Abolishes enzyme activity. Abolishes ability to demethylate N(6)-methyladenosine RNAs (m6A) RNAs; when associated with Q-322.
Alpha-ketoglutarate-dependent dioxygenase FTO
Found in a patient with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities; unknown pathological significance.
In GDFD; has no residual normal activity, impaired ability to demethylate N(6)-methyladenosine RNAs (m6A) RNAs.
Perturbs interaction between N-terminal and C-terminal domains and strongly reduces enzyme activity.
Deamidated asparagine; partial; alternate
Ras-GEF domain-containing family member 1A
Mitochondrial import inner membrane translocase subunit Tim10 B
Putative cancer susceptibility gene HEPN1 protein
In CAPOK; affects the regulation of cell mobility; patient fibroblasts migrate better than control fibroblasts.
In DUH1; affects the regulation of cell mobility resulting in increased melanocyte migration; increased interaction with GNAS; increased interaction with IQGAP1; increased protein levels; increased protein stability.
In DUH1; increased interaction with GNAS; increased interaction with IQGAP1; increased protein levels; increased protein stability.
In DUH1; unknown pathological significance.
Meiotic recombination protein DMC1/LIM15 homolog
In SPG53; found in patients with complex hereditary spastic paraparesis; hypomorphic mutation; does not affect interaction with TSG101 and VPS28.
Vacuolar protein sorting-associated protein 37A
In allele HB-1Y; loss of CTL recognition for epitope HB-1. No influence on HLA-B/HLA-B44 binding, nor on the processing by the proteasome.
In CTRCT3; unknown pathological significance.
In FUCA1D; less than 1% of residual activity.
In FANCC; loss of activity; loss of CDK1-binding and IFNG-induced STAT1-binding; abnormal EIF2AK2 activation and augmented cell death.
No effect on protective function from mitomycin C-genotoxicity.
No effect on protective function from mitomycin C-genotoxicity. Loss of IFNG-induced STAT1-binding.
No effect on protective function from mitomycin C-genotoxicity. No effect on IFNG-induced STAT1-binding.
No loss of protection from cross-linking agent-induced toxicity. No effect on IFNG-induced STAT1-binding.
Phosphoethanolamine/phosphocholine phosphatase
Strongly reduces reactivity toward PEA and PCho substrates. Abolishes phosphatase activity; when associated with N-123.
Strongly reduces reactivity toward PEA and PCho substrates. Abolishes phosphatase activity; when associated with N-43.
In MRT27; unknown pathological significance.
Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-156.
Loss of DNA-binding and inhibition of E2F1-dependent activation. Impairs DNA-binding and dimerization; when associated with A-314.
Pleckstrin homology domain-containing family A member 5
Loss of activity. Acts as a dominant negative mutant.
Loss of activity. No induction of apoptosis.
Receptor-type tyrosine-protein phosphatase H
Rare variant found in patients with X-linked intellectual disability; unknown pathological significance.
Transcription elongation factor A protein-like 2
Abrogates RNA kinase activity and tRNA splicing activity.
Abrogates RNA kinase activity. Abrogates complementation of tRNA splicing activity in yeast; when associated with A-128.
Abrogates complementation of tRNA splicing activity in yeast.
In PCH10; decreases kinase activity, impairs formation of the tRNA splicing endonuclease complex and impairs ability to mediate tRNA splicing and maturation.
Polyribonucleotide 5'-hydroxyl-kinase Clp1
Solute carrier family 2, facilitated glucose transporter member 14
Tumor necrosis factor alpha-induced protein 8
FRAS1-related extracellular matrix protein 2
In CRYPTOP and FRASRS2; decreases cell adhesion; decreases interaction with FREM1.
In FRASRS2; may impair calcium-binding in the 2nd Calx-beta domain; decreases cell adhesion; decreases interaction with FREM1.
Outer dynein arm-docking complex subunit 4
Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase
Zinc finger CCHC domain-containing protein 7
Rho guanine nucleotide exchange factor 12
Loss of kinase activity and ability to activate JNK family.
Mitogen-activated protein kinase kinase kinase kinase 3
Heterogeneous nuclear ribonucleoprotein A1-like 2
Disheveled-associated activator of morphogenesis 1
Forms obligate homodimers under reducing and oxidizing conditions; does not form dodecamer rings under reducing conditions.
In SCAR32; absent protein, reduced glutathione peroxidase activity and reduced PRDX5 protein levels in patient fibroblasts.
In SCAR32; unknown pathological significance.
In SCAR32; unstable protein leading to its degradation, reduced glutathione peroxidase activity and reduced PRDX5 protein levels in patient fibroblasts.
Thioredoxin-dependent peroxide reductase, mitochondrial
Fibronectin type III and SPRY domain-containing protein 1
In mitosis, remained associated with microtubules; when associated with A-313; A-317 and A-322.
In mitosis, remained associated with microtubules; when associated with A-313; A-317 and A-324.
In mitosis, remained associated with microtubules; when associated with A-313; A-322 and A-324.
In mitosis, remained associated with microtubules; when associated with A-317; A-322 and A-324.
Reduced ability to associate with microtubules; when associated with D-313; D-317 and D-324.
Reduced ability to associate with microtubules; when associated with D-313; D-317 and E-322.
Reduced ability to associate with microtubules; when associated with D-313; E-322 and D-324.
Reduced ability to associate with microtubules; when associated with D-317; E-322 and D-324.
Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also enhances DNA-binding to 5'-overhanging flap structures.
Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. Also reduces DNA-binding to 5'-overhanging flap structures.
Abrogates double-stranded DNA exonuclease activity and endonuclease activity against 5'-overhanging flap structures. No effect on DNA-binding to 5'-overhanging flap structures.
May be associated with a reduced risk of colorectal cancer.
May be associated with an increased risk of colorectal cancer.
No rescue of HU-induced degradation and loss of HU-induced increase of phosphorylation. No rescue of HU-induced degradation; when associated with A-621. No rescue of HU-induced degradation; when associated with A-454. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-621.
No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-454 and A-714.
No rescue of HU-induced degradation. No rescue of HU-induced degradation; when associated with A-714. Loss of HU-sensitivity and resistance to HU-induced degradation; when associated with A-621 and A-714.
Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with L-770.
Reduces interaction with MSH2; abrogates interaction with MSH2; when associated with S-640 or E-759.
Abolishes EEF1AKMT4-mediated methylation.
Alters interaction with GRB2; isoform p52Shc (in vitro).
No effect on interaction with GRB2; isoform p52Shc (in vitro).
Decreases tendency towards amyloid formation.
In AMYL8; reduced stability; in contrast to the wild-type, the mutant aggregates into fibrils with classic amyloid-like properties under physiologic solvent conditions.
In IMD43; lower levels of B2M, MHC class I and FCGRT proteins.
Increases tendency towards amyloid formation.
N-linked (Glc) (glycation) isoleucine; in hemodialysis-associated amyloidosis
Pyrrolidone carboxylic acid; in form pI 5.3
Decreases the affinity for IL18 suggesting that the N-linked glycosylation contributes to ligand recognition.
CREB-regulated transcription coactivator 3
Translocates to the cytoplasm. Represses basal TORC3 activity towards CREB.
T-cell immunoglobulin and mucin domain-containing protein 4
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2
N-linked (GlcNAc...) (complex) asparagine; atypical
Scavenger receptor cysteine-rich type 1 protein M160
In SPG35; patients present spastic paraparesis associated with leukodystrophy and dystonia.
In SPG35; significantly reduced enzymatic function.
Confers phosphatase activity. Dephosphorylates MAPK1. Does not affect interaction with FBXW7 and nuclear localization.
Loss of interaction with FBXW7. Does not affect interaction with MAPK1 and nuclear localization.
Serine/threonine/tyrosine-interacting protein
Found in a patient with sporadic amyotrophic lateral sclerosis; unknown pathological significance.
In CMT2F and HMN2B; decreased homodimerization; increased client proteins binding; increased function in chaperone-mediated protein folding; alters CDK5-mediated phosphorylation of neurofilament proteins; alters CDK5-mediated phosphorylation of neurofilament proteins and indirectly impairs their anterograde axonal transport.
In CMT2F; decreased homodimerization only with the wild-type protein; increased client proteins binding; increased function in chaperone-mediated protein folding.
In CMT2F; unknown pathological significance.
In HMN2B and CMT2F; increased aggregation; increased homooligomerization; decreased phosphorylation by MAPKAPK2; changed function in chaperone-mediated protein folding.
In HMN2B; decreased homodimerization; increased client proteins binding; increased function in chaperone-mediated protein folding; alters CDK5-mediated phosphorylation of neurofilament proteins and indirectly impairs their anterograde axonal transport.
In HMN2B; decreased homooligomerization; decreased heterooligomerization with HSPB6; no effect on phosphorylation by MAPKAPK2; decreased function in chaperone-mediated protein folding.
In HMN2B; decreased protein abundance; no effect on oligomerization; increased client proteins binding; no effect on function in chaperone-mediated protein folding; alters CDK5-mediated phosphorylation of neurofilament proteins; indirectly impairs their anterograde axonal transport.
In HMN2B; decreased thermal stability; changed protein structure; changed homooligomerization; loss of heterooligomerization with HSPB6; decreased function in chaperone-mediated protein folding.
In HMN2B; decreased thermal stability; changed protein structure; no effect on homooligomerization; changed heterooligomerization with HSPB6; slightly decreased function in chaperone-mediated protein folding.
In HMN2B; formation of large cytoplasmic aggregates; no effect on dimerization.
In HMN2B; increased aggregation; increased homooligomerization; changed function in chaperone-mediated protein folding.
In HMN2B; induces hyperphosphorylation of neurofilaments; no effect on cytoplasmic location; no effect on dimerization.
In HMN2B; no effect on dimerization; no effect on cytoplasmic location; no effect on dimerization.
In HMN2B; no effect on homodimerization; no effect on client proteins binding; no effect on function in chaperone-mediated protein folding.
In HMN2B; unknown pathological significance.
In HMN2B; unknown pathological significance; no effect on dimerization; no effect on cytoplasmic location; no effect on dimerization.
Mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with D-15 and D-78.
Mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with D-15 and D-82.
Mimicks phosphorylation state, leading to dreased ability to act as molecular chaperones; when associated with D-78 and D-82.
No effect on oligomerization; no effect on client proteins binding; no effect on function in chaperone-mediated protein folding.
Phosphoserine; by MAPKAPK2, MAPKAPK3 and MAPKAPK5
Zinc finger-containing ubiquitin peptidase 1
In CLN1; onset in adulthood; retained in the endoplasmic reticulum rather than reaching the lysosome.
In CLN1; retained in the endoplasmic reticulum rather than reaching the lysosome.
G-patch domain and KOW motifs-containing protein
No loss of interaction with DHX16. Reduced pre-mRNA splicing activity. Decreased ability to suppress the splicing defect observed in dominant-negative DHX16 mutant expressing cells.
Reduced phosphorylation. Significant loss of phosphorylation and increased RNA-binding; when associated with A-27.
Reduced phosphorylation. Significant loss of phosphorylation and increased RNA-binding; when associated with A-316.
Significant loss of interaction with DHX16. No loss of pre-mRNA splicing activity. Able to suppress the splicing defect observed in dominant-negative DHX16 mutant expressing cells.
Cytochrome c oxidase subunit 8A, mitochondrial
Does not convert into a lysine reactive E2; when associated with D-119.
Does not convert into a lysine reactive E2; when associated with D-88.
Loss of catalytic activity. Prevents ubiquitin-dependent proteasomal degradation of UBE2L3.
In AAMR; drastically reduced protein expression.
Mannose-1-phosphate guanyltransferase alpha
Diminished acetylation by both CREBBP/p300 and PCAF. Greatly reduced enhancement of H4 promoter activity.
Greatly diminished acetylation by PCAF. Lesser loss of acetylation by CREBBP/p300. Loss of DNA binding and no enhancement of H4 promoter activity.
Little loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Greater loss of sumoylation; when associated with R-137. Further loss of sumoylation; when associated with R-293. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-137 and R-293.
Some loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Additional small loss of sumoylation; when associated with R-166. Great loss of sumoylation; when associated with R-296. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-166 and R-293.
Some loss of sumoylation. Increases IRF2-mediation activation of ISRE and H4 promoters. Increased inhibition of IRF1-mediated transcription. Further small loss of sumoylation; when associated with R-166. Great loss of sumoylation; when associated with R-137. Abolishes sumoylation. Greatly increased activation of ISRE and H4 promoters and further increased ability to inhibit IRF1-mediated transcription; when associated with R-166 and R-293.
C2 calcium-dependent domain-containing protein 4D
Complete loss of cleavage between SU and TM. Loss of fusiogenic function.
Interchain (between SU and TM chains, or C-189 with C-405); in linked form
Loss of fusiogenic function. No effect on cleavage between SU and TM.
In OOMD8; loss-of-function variant resulting in impaired maternal mRNA decay in fertilized oocytes from the affected individual; abolishes the interaction with CNOT7.
Acid sphingomyelinase-like phosphodiesterase
Acid sphingomyelinase-like phosphodiesterase 3b
In CDCBM3; results in abnormal cellular localization with predominant decoration of microtubules rather than diffuse punctiform cytoplasmic and nuclear distribution as observed for wild-type protein.
Impairs SUMO2 interaction. Loss of SUMO2 interaction; when associated with 22-A--A-25, 76-A--A-79 and 121-A--A-124. Loss of SUMO2-dependent recruitment to DNA-protein cross-links (DPCs); when associated with 22-A--A-25; 76-A--A-79 and 121-A--A-124.
Impairs SUMO2 interaction. Loss of SUMO2 interaction; when associated with 22-A--A-25, 76-A--A-79 and 97-A--A-100. Loss of SUMO2-dependent recruitment to DNA-protein cross-links (DPCs); when associated with 22-A--A-25; 76-A--A-79 and 97-A--A-100.
Impairs SUMO2 interaction. Loss of SUMO2 interaction; when associated with 22-A--A-25, 97-A--A-100 and 121-A--A-124. Loss of SUMO2-dependent recruitment to DNA-protein cross-links (DPCs); when associated with 22-A--A-25; 97-A--A-100 and 121-A--A-124.
Impairs SUMO2 interaction. Loss of SUMO2 interaction; when associated with 76-A--A-79, 97-A--A-100 and 121-A--A-124. Loss of SUMO2-dependent recruitment to DNA-protein cross-links (DPCs); when associated with 76-A--A-79; 97-A--A-100 and 121-A--A-124.
In SPGFX4; unknown pathological significance.
In SPGFX4; unknown pathological significance; requires 2 nucleotide substitutions.
In AKV; no effect on protein abundance; loss of calcium ion transmembrane transport.
In DD; haemorrhagic lesions and neuropsychiatric phenotype.
In DD; mild/moderate/severe form; one patient with epilepsy.
In DD; multiple neuropsychiatric features.
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2
Gamma-aminobutyric acid receptor subunit gamma-1
Leucine-rich repeat-containing protein 4C
In AGM8A, localizes normally to the nucleus, does not perform proper DNA binding, acts in a dominant-negative manner when coexpressed with wild-type) (Ref.29.
tRNA (cytosine(38)-C(5))-methyltransferase
Glycoprotein endo-alpha-1,2-mannosidase-like protein
Found in patients with cartilagenous tumors.
In GLM; somatic mutation; reduces enzymatic activity.
Isocitrate dehydrogenase [NADP], mitochondrial
No appreciable difference in Km for isocitrate and NADP.
Abolishes CXCL10-induced chemotaxis. Reduces CXCL9- and CXCL11-induced chemotaxis. Does not affect binding to CXCL10 and CXCL11.
Abolishes binding to CXCL10 and CXCL11 and CXCL10- and CXCL11-induced chemotaxis. Reduces CXCL9-induced chemotaxis.
Abolishes binding to CXCL10 and CXCL11 and CXCL11-induced chemotaxis. Reduces CXCL9 and CXCL10-induced chemotaxis.
Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis.
Abolishes binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Reduces ligand-induced receptor internalization.
Abolishes binding to CXCL10 and CXCL11. Reduces CXCL9-, CXCL10- and CXCL11-induced chemotaxis.
Does not affect binding to CXCL9, CXCL10 and CXCL11 or activation.
Reduces CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Does not affect binding to CXCL10 and CXCL11 or receptor internalization.
Reduces binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis.
Reduces binding to CXCL10 and CXCL11, and reduces CXCL10- and CXCL11-induced chemotaxis and activation. Does not affect CXCL9-induced chemotaxis and activation.
Reduces binding to CXCL10 and CXCL9- and CXCL11-induced chemotaxis. Abolishes binding to CXCL11 and CXCL10-induced chemotaxis.
Reduces binding to CXCL10 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes binding to CXCL11.
Reduces slightly CXCL9-, CXCL10- and CXCL11-induced chemotaxis.
Reduces sulfation and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes binding to CXCL10. Abolishes sulfation, binding to CXCL11, ligand-induced receptor internalization and CXCL9-, CXCL10- and CXCL11-induced chemotaxis; when associated with F-29.
Reduces sulfation, binding to CXCL10 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis. Abolishes sulfation, binding to CXCL10 and CXCL11 and CXCL9-, CXCL10- and CXCL11-induced chemotaxis; when associated with F-27.
Tetratricopeptide repeat protein 19, mitochondrial
CHD1 helical C-terminal domain containing protein 1
Alpha/beta hydrolase domain-containing protein 17A
Loss of catalytic activity. No effect on its localization. No effect on NRAS plasma membrane localization.
Reduces catalytic activity. Loss of membrane localization. No effect on NRAS plasma membrane localization.
Abolishes phosphorylation by CDK1; 30% reduction in enzymatic activity.
Abolishes phosphorylation and reduces the cell surface expression of CD69 and IL2RA. Reduces association with the actin cytoskeleton.
Found in a patient with isolated coloboma; increases interaction with actin.
Promotes association with the actin cytoskeleton.
Eliminates glutamine-dependent NAD synthetase activity with the ammonia-dependent activity intact.
In VCRL3; decreased protein expression; decreased NAD(+) synthase (glutamine-hydrolyzing) activity.
In VCRL3; no effect on protein expression; decreased NAD(+) synthase (glutamine-hydrolyzing) activity.
Proton acceptor; for glutaminase activity
Decreased interaction with EMC5 and EMC8.
Decreased transmembrane domain binding of tail-anchored proteins.
No effect on transmembrane domain binding of tail-anchored proteins.
No effect on transmembrane domain binding of tail-anchored proteins; when associated with K-61 and E-122.
No effect on transmembrane domain binding of tail-anchored proteins; when associated with K-61 and K-95.
No effect on transmembrane domain binding of tail-anchored proteins; when associated with K-95 and E-122.
In DEE3; disrupts L-glutamate transporter activity.
No effect on activity but response to capsaicin is lost.
Period length of activity extended to 36 minutes.
Period length of activity extended to 42 minutes.
Beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-N-acetylglucosaminyltransferase
Loss of interaction with GOLPH3 and loss of localization to the Golgi.
Pleckstrin homology domain-containing family G member 7
Alters interaction with ZFYVE27 and prevents binding to the FFAT motif in target proteins; when associated with D-94.
Alters interaction with ZFYVE27 and prevents binding to the FFAT motif in target proteins; when associated with D-96.
Vesicle-associated membrane protein-associated protein A
No effect on constitutive activity; when associated with A-104. No effect on constitutive activity; when associated with Q-104.
No effect on constitutive activity; when associated with E-236.
Abolishes uptake of arginine and lysine.
Lysosomal amino acid transporter 1 homolog
BMP-binding endothelial regulator protein
Change in subcellular location: Becomes partially cytosolic and retained in association with the Golgi apparatus. Partial reduction of ubiquitination.
Loss of ITCH-, SMURF2- and WWP1-binding. Partial loss of ubiquitination by ITCH. No effect on STAMBP-binding; when associated with S-99 and S-102. Persistent TNF-mediated NFKBIA phosphorylation. Loss of stimulus-dependent complex formation with TAX1BP1, TNFAIP3 and RIPK1.
Loss of UBE2N-binding. No gain of UBE2L3-binding.
Loss of myristoylation. Change in subcellular location: Becomes diffused throughout the cytosol. Strong reduction of ubiquitination. Reduced efficiency of ITCH-binding.
Loss of phosphorylation and of 14-3-3-binding.
No effect on STAMBP- and SMURF2-binding; when associated with S-102. Persistent TNF-mediated NFKBIA phosphorylation. No effect on STAMBP-binding; when associated with A-40 and S-102. No effect on ubiquitination by ITCH; when associated with S-102. Loss of stimulus-dependent complex formation with TAX1BP1, TNFAIP3 and RIPK1.
No effect on STAMBP- and SMURF2-binding; when associated with S-99. No effect on ubiquitination by ITCH; when associated with S-102. No effect on STAMBP-binding; when associated with A-40 and S-99.
No effect on UBE2N-binding. Gain of UBE2L3-binding.
No effect on UBE2N-binding. No gain of UBE2L3-binding.
No effect on UBE2N-binding. No gain of UBE2L3-binding; when associated with L-127 and L-128.
No effect on UBE2N-binding. No gain of UBE2L3-binding; when associated with L-128.
C-Jun-amino-terminal kinase-interacting protein 1
Phosphothreonine; by MAPK8, MAPK9 and MAPK10
Confers susceptibility to neuroblastoma.
Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma family.
Abolishes phosphorylation by MAPK and translocation to the nucleus following exposure of cells to hydrogen peroxide. No effect on phosphorylation by CDK1 or PRKCD.
Does not affect ability to cleave DNA but abolishes binding to 8-oxoG.
No effect on phosphorylation by CDK1. Greatly reduced phosphorylation by PRKCD. Abolishes phosphorylation by PRKCD; when associated with A-221.
No effect on phosphorylation by MAPK. Significantly reduces phosphorylation by CDK1 and nuclear accumulation. Greatly reduced phosphorylation by PRKCD. Abolishes phosphorylation by PRKCD; when associated with A-6.
No effect on phosphorylation by PRKCD. Abolishes phosphorylation by PKB.
No effect on sumoylation. Abolishes sumoylation; when associated with R-18 and R-214.
No effect on sumoylation. Abolishes sumoylation; when associated with R-18 and R-230.
No effect on sumoylation. Abolishes sumoylation; when associated with R-214 and R-230.
Phosphomimetic mutant which is detected exclusively in the nucleus.
Abolishes translocation of protons and chloride ions.
In MRXSRC; also in patients with complex congenital diaphragmatic hernia; unknown pathological significance; no reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane.
In MRXSRC; has normal localization to structures resembling endoplasmic reticulum membranes; almost abolishes the outwardly-rectifying currents.
In MRXSRC; marked reduction in outwardly-rectifying currents.
In MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum membrane.
In MRXSRC; marked reduction in outwardly-rectifying currents; does not affect its localization in endoplasmic reticulum.
Restores chloride translocation, but not proton transport; when associated with A-281.
Eukaryotic peptide chain release factor subunit 1
NIKS motif; plays an important role in translational termination
No effect on CENPX- and FANCM-binding; loss of double-stranded DNA-binding of the MHF heterodimer and of FANCM recruitment to fork DNA; partial decrease in FA core complex activity, as shown by lower levels of FANCD2 monoubiquitination and higher frequency of sister chromatin exchanges. Complete loss of CENPX- and FANCM-binding; when associated with 87-A-A-88.
Partial loss of CENPX- and FANCM-binding; partial decrease in FA core complex activity, as shown by lower levels of FANCD2 monoubiquitination and higher frequency of sister chromatin exchanges. Complete loss of CENPX- and FANCM-binding; when associated with 73-A-A-74.
Abolishes phosphorylation and MEM-83-activated T-cell adhesion to ICAM1. Abolishes integrin alpha-L/beta-2 activation by CXCL12 and TERF2IP/RAP1. Does not affect heterodimerization of cell surface expression. Does not affect TCR- or phorbol ester-activated T-cell adhesion to ICAM1.
G-protein coupled receptor family C group 5 member D
Found in a patient suspected to suffer from Marfan syndrome; unknown pathological significance.
Found in a patient with Marfan syndrome-like phenotype; unknown pathological significance.
In LDS6; unknown pathological significance.
Loss of phosphorylation by TGFBR1; when associated with A-465 and A-467.
Mothers against decapentaplegic homolog 2
No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-465.
No change in binding to PPM1A. Loss of phosphorylation by TGFBR1; when associated with A-464 and A-467.
Loss of phosphorylation site, and loss of nuclear accumulation. Abolishes phosphorylation by PKB; when associated with A-67.
Loss of phosphorylation site. Reduces interaction with BTRC. Abolishes phosphorylation by PKB; when associated with A-457.
No effect on inhibition of EIF4A1 and on inhibition of translation.
No effect on inhibition of EIF4A1 and on inhibition of translation; when associated with A-333.
No effect on inhibition of EIF4A1 and on inhibition of translation; when associated with A-340.
Reduced inhibition of EIF4A1 helicase activity.
Reduced inhibition of EIF4A1 helicase activity. Strongly reduced inhibition of translation.
Reduced interaction with EIF4A1. Strongly reduced inhibition of translation.
Strongly reduced inhibition of EIF4A1. Strongly reduced inhibition of translation.
Strongly reduced interaction with BTRC. Strongly reduced ubiquitination.
Strongly reduced interaction with EIF4A1.
Strongly reduced interaction with EIF4A1. Reduced inhibition of EIF4A1 helicase activity. Strongly reduced inhibition of translation.
Strongly reduced interaction with EIF4A1. Strongly reduced inhibition of translation.
Strongly reduced interaction with EIF4A1. Strongly reduced inhibition of translation. Reduced inhibition of EIF4A1 helicase activity.
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform
Beta/gamma crystallin domain-containing protein 1
Potassium voltage-gated channel subfamily H member 7
Loss of ubiquitin ligase E3 activity, enhances protein stability. Does not inhibit interaction with APEX1, but inhibits its ubiquitin ligase E3 activity on APEX1. No effect on its ability to induce apoptosis.
No effect on its ability to induce apoptosis.
No loss of ubiquitin ligase E3 activity.
No substantial decrease of ubiquitin ligase E3 activity.
Significant decrease of ubiquitin ligase E3 activity.
Binds preferentially to larger liposomes.
Translocon-associated protein subunit beta
Short transient receptor potential channel 1
Cytochrome b-c1 complex subunit 1, mitochondrial
Suppresses S6K1 phosphorylation by mTORC1.
Biorientation of chromosomes in cell division protein 1
Impaired dimerization; when associated with E-100.
Impaired dimerization; when associated with E-173.
Spindle and kinetochore-associated protein 2
Found in gastric cancer samples; somatic mutation.
Found in prostate cancer samples; somatic mutation; does not up-regulates CDKN1A in a p53-independent manner and significantly reduces cell proliferation.
In BROVCA3; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51.
In FANCO; possibly hypomorphic allele; reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51.
Reduces interaction with BRCA2 and to a lesser extent with PALB2 and RAD51.
Significant loss of function; abolishes Holliday junction resolution activity.
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
In NEDBAS; unknown pathological significance.
Dehydrogenase/reductase SDR family member 4-like 2
Significant destabilization of binding to chromatin.
In ABS1 and DISPORD; significant reduction of activity.
In ABS1; significant reduction of activity.
In DISPORD; significant reduction of activity.
Increases NMD activity and translation stimulation.
Decreased protein stability. Loss of enzyme activity.
In CMARQ3; affects protein stability owing to accelerated proteasomal degradation.
Transport and Golgi organization protein 1 homolog
In MCPH13; results in defective mitotic spindle formation and chromosome segregation; results in delayed mitotic progression.
In TOLCAS; unknown pathological significance.
Partial loss of sumoylation. Complete loss of sumoylation; when associated with R-404.
Partial loss of sumoylation. Complete loss of sumoylation; when associated with R-417.
Ubiquitin carboxyl-terminal hydrolase 19
Voltage-dependent calcium channel gamma-6 subunit
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A
Induces a decrease in enzyme activity due to the inability of cGMP to bind and stimulate enzyme activity.
Mitochondrial import inner membrane translocase subunit Tim23B
Beta-hexosaminidase subunit beta chain A
Beta-hexosaminidase subunit beta chain B
Does not affect the native conformation of the isozyme A. Does not affect hydrolysis of GM2 ganglioside by the isozyme A.
In GM2G2; decreases the isozyme A transport out of the endoplasmic reticulum. Lowers its heat stability. Affects the ability of isozyme A to hydrolyze GM2 ganglioside.
A disintegrin and metalloproteinase with thrombospondin motifs 9
Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A
In ARCL2B; may cause skipping of exon 6.
In ARCL3B; results in a reduction of protein expression in skin fibroblasts from the patient.
Pyrroline-5-carboxylate reductase 1, mitochondrial
In MGCA8; may lead to skipping of exon 7 and the resultant protein may be truncated; loss of protein expression in patient cells homozygous for the mutation.
Loss of interaction with XIAP. Loss of inhibition of XIAP activity.
May be a risk factor for Parkinson disease; reduced protease activity.
In MC3DN8; results in impaired incorporation of the Rieske Fe-S protein into the CIII complex.
Greatly diminishes interaction with ubiquitin; when associated with G-369.
Greatly diminishes interaction with ubiquitin; when associated with G-372.
Greatly diminishes interaction with ubiquitin; when associated with G-376.
Changed acetylcholine-gated cation-selective channel activity.
In CMS1A; causes increased channel opening in absence of ACh; prolonged opening in presence of ACh; increased affinity for ACh and enhanced desensitization.
In CMS1A; increases the rate of channel opening and slows the rate of channel closing but has no effect on agonist binding.
In CMS1B; abnormally slow channel opening and closing resulting in abnormally brief current.
In CMS1B; fewer and shorter ion channel activations with decreased channel opening rate and increased channel closing rate.
In CMS1B; markedly reduced protein expression.
In CMS1B; mutant channel shows an approximately 30-fold decrease of ACh binding affinity for the second of 2 closed-state binding sites but only a 2-fold decrease in gating efficiency.
In NEDHFBA; unknown pathological significance.
Protein phosphatase 1 regulatory subunit 21
Ankyrin repeat domain-containing protein 37
Factor VIIIa heavy chain, 200 kDa isoform
Factor VIIIa heavy chain, 92 kDa isoform
In HEMA; East Hartford; severe/moderate/mild; abolishes thrombin cleavage at the light chain.
In HEMA; Kumamoto; mild/moderate; abolishes the normal cleavage by thrombin.
In HEMA; Okayama; moderate/severe; abolishes the normal cleavage by thrombin.
In HEMA; mild-moderate; affinity for VWF reduced 8-fold.
In HEMA; mild/moderate; secretion impaired.
In HEMA; mild; abolishes normal cleavage by thrombin.
In HEMA; mild; abolishes thrombin cleavage at the light chain.
In HEMA; mild; may cause reduced phospholipid binding.
In HEMA; mild; unknown pathological significance; decreases binding with VWF and phospholipid; no effect on reaction with F9, F2 and F10; decreases specific activity by 30%; patient develops inhibitor alloantibodies.
In HEMA; moderate/mild; may cause reduced phospholipid binding.
In HEMA; moderate; affinity for VWF reduced 80-fold.
In HEMA; requires 2 nucleotide substitutions.
In HEMA; severe/mild; affinity for VWF reduced 3-fold.
In HEMA; severe/moderate; may cause reduced phospholipid binding.
In HEMA; severe; abolishes the normal cleavage by thrombin.
In HEMA; unknown pathological significance.
Zinc finger and SCAN domain-containing protein 5A
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Decreased cell-cell adhesion; no effect on subcellular localization; no effect on neurite outgrowth.
Found in a patient with L1 syndrome; unknown pathological significance.
In HSAS and MASA; also found in a patient with the diagnosis of L1 syndrome; also in a patient with hydrocephalus and Hirschsprung disease.
In HSAS and MASA; also in a patient with hydrocephalus and Hirschsprung disease.
In HSAS and MASA; associated with callosal agenesis; also found in a patient affected by hydrocephalus with Hirschsprung disease.
In HSAS and MASA; decrease in neurite outgrowth, when assayed in NGF-treated pheochromocytoma PC12 cells; decrease in cell-matrix adhesion; decreased cell migration; no effect on the localization at the cell surface; no effect on cell proliferation, when transfected in pheochromocytoma PC12 cells.
In HSAS; decrease in cell-matrix adhesion; decreased cell migration; no effect on the localization at the cell surface; no effect on cell proliferation, when transfected in pheochromocytoma PC12 cells; no effect on neurite outgrowth, when assayed in NGF-treated pheochromocytoma PC12 cells.
In HSAS; partial loss of axon guidance and loss of proper synapse formation, when assayed in a heterologous system.
In HSAS; partial loss of localization at the cell surface; retention in the endoplasmic reticulum; in neurons, partial loss of localization to axons, but enriched on proximal dendrites.
In HSAS; severe; loss of localization to the cell surface; retention in the endoplasmic reticulum; loss of axon guidance, when assayed in a heterologous system.
In HSAS; severe; reduced axon arborization; partial loss of localization at the cell surface; retention in the endoplasmic reticulum; in neurons, restricted to cell bodies and proximal segments of processes; loss of axon guidance and of proper synapse formation, when assayed in a heterologous system.
In MASA; associated with callosal agenesis.
In MASA; decrease in cell-matrix adhesion; decreased cell migration; loss of axon guidance and of proper synapse formation, when assayed in a heterologous system; no effect on the localization at the cell surface; no effect on cell proliferation, when transfected in pheochromocytoma PC12 cells; no effect on neurite outgrowth, when assayed in NGF-treated pheochromocytoma PC12 cells.
In MASA; decrease in neurite outgrowth, when assayed in NGF-treated pheochromocytoma PC12 cells; decrease in cell-matrix adhesion; decreased cell migration; no effect on axon guidance, on subcellular location to synaptic terminals, nor on proper synapse formation, when assayed in a heterologous system; no effect on the localization at the cell surface; no effect on cell proliferation, when transfected in pheochromocytoma PC12 cells.
In MASA; loss of homophilic interactions at the cell surface; no effect on localization at the cell surface.
Loss of axon guidance, when assayed in a heterologous system, but normal synapse formation.
No effect on axon guidance activity, nor on synapse formation, when assayed in a heterologous system.
No effect on localization at the cell surface.
Probable disease-associated variant found in L1 syndrome.
Probable disease-associated variant found in L1 syndrome; loss of localization at the cell surface; retention in the endoplasmic reticulum; loss of homophilic interactions at the cell surface.
Probable disease-associated variant found in L1 syndrome; loss of localization at the cell surface; retention in the endoplasmic reticulum; loss of transport into axons; loss of neurite outgrowth; loss of cell-cell adhesion.
Probable disease-associated variant found in L1 syndrome; requires 2 nucleotide substitutions.
Probable disease-associated variant found in a patient with L1 syndrome; loss of homophilic interactions at the cell surface; no effect on the localization at the cell surface.
Complete loss of ubiquitination by RNF186.
Abolishes the interaction with NCOA1; when associated with A-802.
Abolishes the interaction with NCOA1; when associated with A-805.
Signal transducer and activator of transcription 6
In MKS13 and OFD16; does not affect subcellular location at ciliary transition zone; significantly decreases cilium assembly from patient's skin primary fibroblast; impairs protein localization to cilium from patient's skin primary fibroblast.
In OFD16; does not affect subcellular location at ciliary transition zone.
In PHA2B; impaired interaction with KLHL3.
Decreased stearoylation in response to S.flexneri infection.
Abolishes ligase activity. No effect on mitochondrial localization.
Failure to reduce TP53 levels and abolishes ligase activity; when associated with S-302.
Failure to reduce TP53 levels and abolishes ligase activity; when associated with S-305.
Mitochondrial ubiquitin ligase activator of NFKB 1
Protein is targeted to the ER; when associated with A-260.
Protein is targeted to the ER; when associated with A-261.
Rho guanine nucleotide exchange factor 10-like protein
BTB/POZ domain-containing protein KCTD17
In DYT26; does not affect cytoplasmic subcellular location.
Abolishes sumoylation; when associated with R-732.
Abolishes sumoylation; when associated with R-774.
Does not affect sumoylation of the protein.
Slightly affects interactions with steroid receptors. Abolishes interactions with steroid receptors; when associated with A-636; A-637; A-693 and A-694.
Slightly affects interactions with steroid receptors. Abolishes interactions with steroid receptors; when associated with A-636; A-637; A-752 and A-753.
Slightly affects interactions with steroid receptors. Abolishes interactions with steroid receptors; when associated with A-693; A-694; A-752 and A-753.
Binding L-selectin reduced by 20%, neutrophil recruitment reduced by 30%, and lymphocyte rolling reduced by 32%; when associated with F-46. Binding L-lectin reduced by 31%, neutrophil recruitment reduced by 52%, and lymphocyte rolling reduced by 52%; when associated with F-51. Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-46 and F-51. Binding of L-selectin reduced by 91%; when associated with F-46; F-51 and A-57.
Binding L-selectin reduced by 20%, neutrophil recruitment reduced by 30%, and lymphocyte rolling reduced by 32%; when associated with F-48. Binding L-selectin reduced by 86%, neutrophil recruitment reduced by 75%, and lymphocyte rolling reduced by 69%; when associated with F-51. Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-48 and F-51. Binding of L-selectin reduced by 91%; when associated with F-48; F-51 and A-57.
Binding L-selectin reduced by 86%, neutrophil recruitment reduced by 75% and, lymphocyte rolling reduced by 69%; when associated with F-46. Binding L-selectin reduced by 31%, neutrophil recruitment reduced by 52%, and lymphocyte rolling reduced by 52%; when associated with F-48; Binding L-selectin reduced by 89%, and neutrophil recruitment reduced by 90%; when associated with F-46 and F-48. Binding of L-selectin reduced by 91%; when associated with F-46; F-48 and A-57.
In short form; not an alternative splicing.
No E- nor P-selectin binding, and very little neutrophil rolling. Binding of L-selectin reduced by 91%; when associated with F-46; F-48 and F-51.
No dimer formation. No effect on P-selectin binding.
No effect on L-selectin binding nor neutrophil rolling.
No sulfation. Almost complete loss of P-selectin binding. No effect on E-selectin binding.
Abolishes S-nitrosylation. No stimulation of guanine nucleotide exchange.
Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane. No effect on subcellular location of isoform 2.
Exclusively localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-184.
Found in a patient with severe fetal hydrops and pleural effusion; unknown pathological significance; decreased activation of Ras protein signal transduction.
GTP-binding activity reduced by factor of 25.
GTP-binding activity reduced by factor of 30.
In CSTLO and CMEMS; also found in patients with oral squamous cell carcinoma.
In CSTLO, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane.
In H-Ras-3KR mutant; decreased fatty-acylation.
In NMTC2; somatic mutation; increases transformation of cultured cell lines.
In SFM; somatic mutation; shows constitutive activation of the MAPK and PI3K-AKT signaling pathways.
In melanoma; strongly reduced GTP hydrolysis in the presence of RAF1; increases transformation of cultured cell lines.
Increased Ras signaling due to impaired ubiquitination.
Loss of GTPase activity and creation of an autophosphorylation site.
Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine stimulation of Ras-GTPase activity. Mainly localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-181.
Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12.
Loss of interaction with PLCE1; when associated with V-12.
Moderately increased transformation of cultured cell lines.
N-acetylmethionine; in GTPase HRas; alternate
N-acetylthreonine; in GTPase HRas, N-terminally processed
No effect on interaction with PLCE1; when associated with V-12.
S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate
Strongly increased transformation of cultured cell lines.
CCR4-NOT transcription complex subunit 3
In IDDSADF; unknown pathological significance.
Abolishes colocalization with ORAI1 and activation of CRAC channels.
Constitutive activation of CRAC channels.
Constitutive localization in punctae at the cell membrane and constitutive activation of CRAC channels.
Constitutive localization in punctae at the cell membrane and constitutive activation of CRAC channels; when associated with D-108.
Constitutive localization in punctae at the cell membrane and constitutive activation of CRAC channels; when associated with D-110.
In STRMK; autosomal dominant; promotes constitutive activation of the Ca(2+) release-activated Ca(2+) (CRAC) channel.
In TAM1; increases store-operated Ca(2+) influx.
In TAM1; myoblasts with the mutation have significantly increased clustering of STIM1, regardless of calcium levels, indicating that calcium sensing in the sarcoplasmic reticulum is impaired.
Increases Ca(2+) influx even when Ca(2+) stores are not depleted.
Increases Ca(2+) influx even when Ca(2+) stores are not depleted. Promotes constitutive activation of the Ca2+ release-activated Ca2+ (CRAC) channel.
Increases Ca(2+) influx through activation of CRAC channels, even when Ca(2+) stores are not depleted.
Loss of interaction with MAPRE1 and association with the growing microtubule plus ends.
Probable disease-associated variant found in a patient with autosomal recessive hypomaturation enamel malformations, nail dysplasia and frequent throat infections.
Promotes constitutive activation of the Ca2+ release-activated Ca2+ (CRAC) channel.
In CDG1J; strongly reduced enzyme activity.
In CMS13; mildly reduced enzyme activity.
In CMS13; strongly reduced enzyme activity.
No significant effect on enzyme activity.
Reduces binding to inhibitor. Nearly abolishes enzyme activity.
UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase
Reduced DNA/RNA binding; when associated with A-825.
Reduced DNA/RNA binding; when associated with A-828.
Zinc finger and BTB domain-containing protein 22
Decreases affinity for PHC2. Abolishes interaction with PHC2; when associated with E-174.
Increases stimulation of RNF2 ubiquitin ligase activity; when associated with E-77.
Increases stimulation of RNF2 ubiquitin ligase activity; when associated with N-73.
Mildly decreases histone H2A ubiquitination. Strongly decreases histone H2A ubiquitination; when associated with A-62.
Strongly decreases affinity for PHC2. Abolishes interaction with PHC2; when associated with E-165.
Strongly decreases histone H2A ubiquitination; when associated with A-64.
Glucose-fructose oxidoreductase domain-containing protein 1
In HH20; rare variant associated with susceptibility to disease; some patients have a second mutation in another HH-associated gene including FGFR1, HS6ST1 and FLRT3; the mutant has reduced ability to activate FGFR1.
In HH20; the mutant has reduced ability to activate FGFR1.
cAMP-dependent protein kinase inhibitor alpha
Ankyrin repeat domain-containing protein 49
Loss of interaction with GOPC. No effect on interaction LIN7B and MAGI1.
Loss of interaction with LIN7B, MAGI1 and GOPC.
No effect on interaction with LIN7B, MAGI1 and GOPC.
Associated with ICH susceptibility; results in a significantly decreased extracellular-to-intracellular ratio of COL4A2 and COL4A1 proteins, indicating interference with the proper secretion of both these proteins.
Does not affect COL4A2 and COL4A1 secretion.
Probable disease-associated variant found in a family with porencephaly and small-vessel disease in the form of scattered white matter lesions; impairs COL4A2 and COL4A1 secretion; the mutant protein is retained in the endoplasmic reticulum.
Putative potassium voltage-gated channel subfamily E member 1B
T-cell activation Rho GTPase-activating protein
Thyrotropin-releasing hormone-degrading ectoenzyme
Glutamine amidotransferase-like class 1 domain-containing protein 1
Cell death-inducing p53-target protein 1
Does not affect DNA glycosylase activity.
Does not affect DNA glycosylase activity; does not affect function in DNA repair.
Found in a case of sporadic lung cancer; unknown pathological significance; loss of function in DNA repair.
Found in a family with non-polyposis colorectal cancer-like syndrome; unknown pathological significance; does not affect function in DNA repair.
Found in multiple polyposis and sporadic colorectal cancer cases; unknown pathological significance; does not affect DNA glycosylase activity; does not affect function in DNA repair.
Found in patient with multiple polyposis; unknown pathological significance; does not affect function in DNA repair.
Found in sporadic colorectal cancer cases; unknown pathological significance; decreased function in DNA repair.
Found in sporadic hepatocellular carcinoma; unknown pathological significance; loss of function in DNA repair.
In FAP2; also found in a case of sporadic colorectal cancer; loss of DNA glycosylase activity; loss of DNA binding; loss of function in DNA repair.
In FAP2; also found in a case of sporadic colorectal cancer; unknown pathological significance; decreased function in DNA repair.
In FAP2; also found in a patient with multiple polyps; unknown pathological significance; does not affect function in DNA repair.
In FAP2; also found in multiple polyposis and colorectal cancer cases; loss of DNA glycosylase activity; loss of function in DNA repair.
In FAP2; also found in multiple polyposis and colorectal cancer cases; loss of function in DNA repair.
In FAP2; also found in multiple polyposis case; unknown pathological significance; reduced DNA glycosylase activity; no effect on function in DNA repair.
In FAP2; also found in multiple polyposis cases; loss of DNA glycosylase activity; loss of function in DNA repair.
In FAP2; also found in multiple polyposis cases; loss of function in DNA repair.
In FAP2; also found in multiple polyposis cases; unknown pathological significance; does not affect DNA glycosylase activity; slightly decreased function in DNA repair.
In FAP2; also found in multiple polyposis, colorectal and lung cancer cases; unknown pathological significance; decreased function in DNA repair.
In FAP2; also found in patient with multiple polyps and in a family with non-polyposis colorectal cancer-like syndrome; unknown pathological significance; does not affect function in DNA repair.
In FAP2; decreased function in DNA repair.
In FAP2; found also in sporadic colorectal cancer cases; unknown pathological significance; decreased function in DNA repair.
In FAP2; loss of DNA glycosylase activity; decreased DNA binding; loss of function in DNA repair.
In FAP2; loss of DNA glycosylase activity; loss of DNA binding; loss of function in DNA repair.
In FAP2; loss of DNA glycosylase activity; loss of function in DNA repair.
In FAP2; loss of function in DNA repair.
In FAP2; reduced DNA glycosylase activity.
In FAP2; reduced DNA glycosylase activity; decreased DNA binding; decreased function in DNA repair.
In FAP2; reduced DNA glycosylase activity; decreased DNA binding; loss of function in DNA repair.
In FAP2; unknown pathological significance.
In FAP2; unknown pathological significance; does not affect function in DNA repair.
In GASC; sporadic; decreased function in DNA repair.
In GASC; sporadic; unknown pathological significance; does not affect function in DNA repair.
In isoform Beta-1, isoform Gamma-2 and isoform Gamma-3.
Likely benign variant; does not affect DNA glycosylase activity.
Likely benign variant; does not affect DNA glycosylase activity; does not affect function in DNA repair.
Probable disease-associated variant found in a case of familial colorectal cancer; no significant effect on DNA glycosylase activity; slightly decreased function in DNA repair.
Probable disease-associated variant found in multiple polyposis cases; decreased function in DNA repair.
Reduced DNA glycosylase activity; decreased function in DNA repair.
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta
Cleavage stimulation factor subunit 2 tau variant
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2
Pleckstrin homology domain-containing family G member 1
Fumarylacetoacetate hydrolase domain-containing protein 2A
39S ribosomal protein L50, mitochondrial
B-cell scaffold protein with ankyrin repeats
Abolished formation of a complex with core nucleosome and HPF1, leading to abolished ability to catalyze serine ADP-ribosylation of histones.
Abolished formation of a complex with core nucleosome and HPF1, leading to abolished ability to catalyze serine ADP-ribosylation of histones. Abolished DNA-induced ADP-ribosyltransferase activity. Abolished trapping at DNA damage sites upon binding to PARP inhibitors (PARPi).
Abolished poly [ADP-ribose] polymerase activity without affecting localization to DNA damage sites.
Abolished trapping at DNA damage sites upon binding to PARP inhibitors (PARPi).
Decreased poly [ADP-ribose] polymerase activity.
Decreased poly [ADP-ribose] polymerase activity. Impaired formation of a complex with damaged DNA.
Does not affect DNA-induced ADP-ribosyltransferase activity.
Does not affect poly [ADP-ribose] polymerase activity.
For poly [ADP-ribose] polymerase activity
In PARP2-QFRD mutant; induces conformational change that bridges nucleosomes by binding to linker DNA ends and promotes interaction with HPF1.
Increased DNA-induced ADP-ribosyltransferase activity.
Reduced DNA-induced ADP-ribosyltransferase activity.
Reduced localization to the nucleus. Abolished localization to the nucleus; when associated with 21-A-A-22.
Reduced localization to the nucleus. Abolished localization to the nucleus; when associated with 37-A-A-38.
Reduced recruitment to DNA damage sites. Abolished DNA-induced ADP-ribosyltransferase activity.
Reduced recruitment to DNA damage sites. Decreased poly [ADP-ribose] polymerase activity.
Strongly reduced serine ADP-ribosylation, caused by abolished interaction with HPF1.
In PXE; acts as a modifier of disease severity; more frequent in patients with a severe disease course.
17% reduction in ternary complex formation.
34% reduction in ternary complex formation.
9-fold increase in transcriptional activator activity; when associated with R-230. Reduction in sumoylation.
9-fold increase in transcriptional activator activity; when associated with R-249. Reduction in sumoylation.
No effect on ternary complex formation but loss of transcriptional activity positive regulation by MAD2L2.
Slight reduction in ternary complex formation.
Long-chain fatty acid transport protein 6
Outer dense fiber protein 3-like protein 1
Abolishes interaction with UPF1; reduces NMD efficiency.
Abolishes interaction with UPF3B and association with SMG1 and RBM8A; reduces phosphorylation of UPF1.
Decreases interaction with UPF1; does not reduce NMD efficiency.
Does not abolish interaction with UPF3B.
Does not abolish interaction with UPF3B. Does not abolish interaction with UPF3B; when associated with D-854.
Does not abolish interaction with UPF3B; when associated with K-851 and R-852.
Does not impair RNA-binding; when associated with A-894.
Does not impair RNA-binding; when associated with A-932.
Greatly reduces NMD efficiency; when associated with E-1171 and E-1173.
Greatly reduces NMD efficiency; when associated with E-1171 and E-1174.
Greatly reduces NMD efficiency; when associated with E-1173 and E-1174.
Decreases PS- and PE-dependent ATPase activity of ATP11C:TMEM30A; when associated with A-132 and A-133.
Decreases PS- and PE-dependent ATPase activity of ATP11C:TMEM30A; when associated with A-132 and A-136.
Decreases PS- and PE-dependent ATPase activity of ATP11C:TMEM30A; when associated with A-133 and A-136.
Abolished binding to 'Lys-29'- and 'Lys-33'-linked ubiquitin.
Abolished binding to 'Lys-33'-linked diubiquitin.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with 14-LV-15; A-90; 94-LV-95; A-155 and 159-LV-160.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; 94-LV-95; A-155 and 159-LV-160.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; 94-LV-95 and 159-LV-160.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; 94-LV-95; and A-155.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; 14-LV-15; A-90; A-155 and 159-LV-160.
Abolishes the binding to ubiquitin chains but not the deubiquitinating activity; when associated with A-10; A-90; 94-LV-95; A-155 and 159-LV-160.
Abolishes the deubiquitinating activity but not the binding to ubiquitin chains.
Does not affect binding to 'Lys-29'- and 'Lys-33'-linked ubiquitin.
Strongly reduced binding to 'Lys-29'- and 'Lys-33'-linked ubiquitin.
Strongly reduced binding to 'Lys-33'-linked diubiquitin.
Ankyrin repeat domain-containing protein 9
Important role in both nutrient sensing and binding/regulation of IMPDH2
Inhibits the vesicle-to-rods transition under nutrient-limiting conditions. Inhibits the vesicle-to-rods transition under nutrient-limiting conditions; when associated with C-109. Does not affect the abundance of IMPDH2.
Inhibits the vesicle-to-rods transition under nutrient-limiting conditions. Inhibits the vesicle-to-rods transition under nutrient-limiting conditions; when associated with C-110. Prevents the colocalization of ANKRD9 with IMPDH2 filaments. Increases the abundance of IMPDH2. Increases the abundance of IMPDH2; when associated with C-110.
Loss the vesicle-like pattern and becomes diffuse in the cytosol.
Does not affect protein nuclear localization.
Found in a patient with frontotemporal lobar degeneration.
In ALS6; results in aberrant trafficking and cytoplasmic retention of the protein.
In ALS6; unknown pathological significance.
3-oxoacyl-[acyl-carrier-protein] reductase
Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant.
Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant. Increases NADPH-dependent reductase activity with acetoacetyl-CoA. Reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activities.
Strongly reduced ability to restore growth of an OAR1-deficient yeast mutant. Strongly reduces NADPH-dependent reductase activity with acetoacetyl-CoA and 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activities.
Unable to restore growth of an OAR1-deficient yeast mutant.
Unable to restore growth of an OAR1-deficient yeast mutant. Abolishes NADPH-dependent reductase activity with acetoacetyl-CoA. Strongly reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activities.
Unable to restore growth of an OAR1-deficient yeast mutant. Increases NADPH-dependent reductase activity with acetoacetyl-CoA. Reduces NADPH-dependent reductase activity with 9,10-phenanthrene quinone. No effect on NADH-dependent reductase activities.
Peroxisome proliferator-activated receptor gamma coactivator 1-beta
Reduces interaction and activation of ESR1. Loss of interaction and activation of ESR1; when associated with 155-AAQKAA-160.
Reduces interaction and activation of ESR1. Loss of interaction and activation of ESR1; when associated with 343-AREAA-347.
Loss of zinc transporter activity. No effect on localization to the trans-Golgi network.
No effect on zinc ion transmembrane transporter activity. No effect on zinc ion import into Golgi. Loss of specificity for zinc ions as it can also transport cadmium ions.
No effect on zinc transporter activity. No effect on localization to the trans-Golgi network.
Impaired interaction with 14-3-3 proteins and increased EGF-independent cell proliferation; when associated with A-210.
Impaired interaction with 14-3-3 proteins and increased EGF-independent cell proliferation; when associated with A-391.
Tumor necrosis factor alpha-induced protein 2
Heterogeneous nuclear ribonucleoprotein H2
Heterogeneous nuclear ribonucleoprotein H2, N-terminally processed
N-acetylmethionine; in Heterogeneous nuclear ribonucleoprotein H2, N-terminally processed
FYVE and coiled-coil domain-containing protein 1
In CTRCT18; unknown pathological significance.
In palmoplantar keratoderma; and mild ichthyosis largely limited to the flexural areas.
In HADDS; according to PubMed:28017373 shows significant loss of transcriptional activator activity while according to PubMed:28017370 shows partial loss of transcriptional activator activity; localizes both in the cytoplasm and the nucleus; decreased chromatin-binding.
In HADDS; loss of transcriptional activator activity.
In HADDS; partial loss of transcriptional activator activity.
In HADDS; significant loss of transcriptional activator activity.
In HADDS; significant loss of transcriptional activator activity; localizes both in the cytoplasm and the nucleus; decreased chromatin binding.
In HADDS; significant loss of transcriptional activator activity; localizes both in the cytoplasm and the nucleus; decreased chromatin-binding.
Baculoviral IAP repeat-containing protein 6
Receptor-type tyrosine-protein phosphatase O
Cytochrome c oxidase assembly protein COX18, mitochondrial
(Microbial infection) ADP-ribosylasparagine; by botulinum toxin
(Microbial infection) O-AMP-threonine; by Vibrio VopS
(Microbial infection) O-AMP-tyrosine; by Haemophilus IbpA; alternate
(Microbial infection) O-alpha-linked (GlcNAc) threonine; by C.novyi toxin TcdA; alternate
(Microbial infection) O-linked (Glc) threonine; by C.difficile toxins TcdA and TcdB; alternate
(Microbial infection) O-linked (GlcNAc) tyrosine; by Photorhabdus PAU_02230; alternate
Abolished monoglucosylation by C.difficile toxin TcdA. Abolished O-GlcNAcylation by C.novyi toxin TcdA.
Abolishes AMPylation by Haemophilus IbpA.
Converts geranyl-geranylation to farnesylation; does not prevent the cleavage by yopT.
Decreased Rho protein signal transduction. Decreased substrate adhesion-dependent cell spreading. Decreased stress fibers assembly. Decreased cytoplasmic microtubule organization.
In EDFAOB; somatic mosaic variant; decreased Rho protein signal transduction; decreased substrate adhesion-dependent cell spreading; decreased number of stress fibers assembly; decreased cytoplasmic microtubule organization.
In EDFAOB; somatic mosaic variant; decreased Rho protein signal transduction; decreased substrate adhesion-dependent cell spreading; decreased stress fibers assembly; decreased cytoplasmic microtubule organization.
Increased Rho protein signal transduction. Constitutively active.
Probable proton-coupled zinc antiporter SLC30A4
Suppresses homodimerization, TNFR1 interaction, and apoptosis induction.
Suppresses homodimerization, and TNFR1 interaction.
Tumor necrosis factor receptor superfamily member 25
Abolishes N-glycosylation; when associated with Q-10.
Abolishes N-glycosylation; when associated with Q-20.
No effect on inhibitor binding; abolishes catalytic activity. Abolishes proteolysis of PSEN1. Abolishes proteolysis of XBP1 isoform 1 and increases interaction with XBP1 isoform 1.
In NS14; results in loss of MAPK down-regulation; increased protein degradation.
In NS14; results in loss of MAPK down-regulation; increased protein degradation; properly targeted to the cell membrane; loss of interaction with NF1.
No effect on phosphorylation or ubiquitination.
No effect on phosphorylation or ubiquitination; when associated with F-264.
No effect on phosphorylation or ubiquitination; when associated with F-266.
Reduces ubiquitination and CBL-induced phosphorylation; when associated with F-228.
Reduces ubiquitination and CBL-induced phosphorylation; when associated with F-231.
Sprouty-related, EVH1 domain-containing protein 2
In IGS2; loss of interaction with CUBN; strongly reduced CUBN expression at the cell surface.
In IGS2; reduced presence at the cell membrane; loss of interaction with CUBN; reduced CUBN expression at the cell surface.
Loss of expression at the cell membrane.
Loss of interaction with CUBN and strongly reduced CUBN expression at the cell surface.
Electron transfer flavoprotein subunit alpha, mitochondrial
In GA2A; decreased electron transfer activity.
In GA2A; impaired protein stability and loss of electron transfer activity.
Steroid receptor-associated and regulated protein
Abolishes binding to DNA and has diffuse nuclear localization.
In CVID13; abolishes binding to DNA; has diffuse nuclear localization.
In CVID13; decreases binding to pericentromeric heterochromatin DNA; has diffuse nuclear localization.
Meiotic recombination protein REC8 homolog
In S100Ppa; permanently active, interacts with EZR and PPP5C in absence of calcium; when associated with 21-S--G-23, C-64 and K-68.
In S100Ppa; permanently active, interacts with EZR and PPP5C in absence of calcium; when associated with 21-S--G-23, C-64 and S-73.
In S100Ppa; permanently active, interacts with EZR and PPP5C in absence of calcium; when associated with 21-S--G-23, K-68 and S-73.
In S100Ppa; permanently active, interacts with EZR and PPP5C in absence of calcium; when associated with C-64, K-68 and S-73.
Heterogeneous nuclear ribonucleoprotein D-like
Reduces significantly its nuclear localization.
(Microbial infection) ADP-ribosyldiphthamide
In SCA26; compromises the mechanics of translocation.
Strongly reduced phosphorylation at Thr-57.
N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 4
In MCIDDS; unknown pathological significance; mildly decreased function in potassium transmembrane transport.
Potassium voltage-gated channel subfamily A member 4
ATP-binding cassette sub-family A member 9
Abolishes DNA lyase activity. No effect on DNA polymerase activity.
Abolishes DNA polymerase and DNA lyase activity.
Abolishes ubiquitination; when associated with R-41 and R-61.
Abolishes ubiquitination; when associated with R-41 and R-81.
Abolishes ubiquitination; when associated with R-61 and R-81.
Slight effect. Abolishes methylation by PRMT6 and impairs the polymerase activity; when associated with K-152.
Slight effect. Abolishes methylation by PRMT6 and impairs the polymerase activity; when associated with K-83.
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)
MAM and LDL-receptor class A domain-containing protein 1
Associated with high serum levels of uric acid and increased risk of gout; results in lower urate transport rates compared to wild-type; decreased protein abundance.
Broad substrate specificity ATP-binding cassette transporter ABCG2
Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Decreased substrate transport.
Decreased protein abundance. Decreased localization to the plasma membrane and retained intracellularly. Loss of ATPase-coupled transmembrane transporter activity.
Decreased protein abundance. No effect on substrate transmembrane transport.
Decreased protein abundance; decreased localization to the plasma membrane; no effect on ATPase-coupled transmembrane transporter activity.
Decreased protein abundance; loss of localization to the plasma membrane.
Decreased protein abundance; no effect on localization to the plasma membrane; no effect on substrate transmembrane transport; decreased ATPase activity; no effect on ATPase-coupled transmembrane transporter activity.
Loss of phosphorylation by PIM1. Constitutive drug resistance independent of PIM1.
Loss of phosphorylation by PIM1. Decreased localization to the plasma membrane. Decreased homooligomerization. Loss of function in resistance to drug treatment.
Loss of protein expression; loss of localization to the plasma membrane.
No effect on protein abundance; no effect on localization to the plasma membrane; increased ATPase activity; decreased ATPase-coupled transmembrane transporter activity.
No effect on protein abundance; no effect on localization to the plasma membrane; no effect on ATPase activity; decreased ATPase-coupled transmembrane transporter activity.
No effect on protein abundance; no effect on localization to the plasma membrane; no effect on ATPase activity; no effect on substrate transmembrane transport.
No effect on protein abundance; no effect on substrate transmembrane transport.
No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Decreased substrate transport.
No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased basal and substrate-induced ATP hydrolysis. Decreased substrate transport.
No effect on stability. Increased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased basal and substrate-induced ATP hydrolysis. Increased substrate transport.
No effect on stability. Increased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased substrate-induced ATP hydrolysis. Increased substrate transport.
No effect on stability. No effect on estrone-3 sulfate ATPase-coupled transmembrane transporter activity. No effect on substrate-induced ATP hydrolysis. No effect on substrate transport.
Strongly reduced binding to hemin but not to PPIX.
Thioredoxin domain-containing protein 17
Impaired acetylation, leading to reduced kinetochore-microtubule attachment; when associated with R-53.
Impaired acetylation, leading to reduced kinetochore-microtubule attachment; when associated with R-59.
Mimics acetylation, leading to increased kinetochore-microtubule attachment; when associated with Q-53.
Mimics acetylation, leading to increased kinetochore-microtubule attachment; when associated with Q-59.
Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1
Loss of GAP activity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C.
Loss of binding to PIP2 and PIP3. Loss of association with endosomal tubules when coexpressed with PIP5K1C.
Loss of phosphorylation at S-554, interaction with ITGB1 and ITGB1-dependent cell migration.
Loss of phosphorylation by PKB, interaction with ITGB1 and ITGB1-dependent cell migration.
Preserves membrane binding and ability to tubulate liposomes.
Reduced membrane binding and ability to induce liposome tubulation.
Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-636.
Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-527 and A-639.
Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-312; A-636 and A-639.
Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-307; A-527; A-636 and A-639.
Impaired degradation by the Cul7-RING(FBXW8) complex; when associated with A-312; A-527; A-636 and A-639.
May contribute to insulin resistance by impairing metabolic signaling through PI3K-dependent pathways.
Phosphoserine; by IKKB, MAPK8 and RPS6KB1
Cilia- and flagella-associated protein 77
Mesenteric estrogen-dependent adipogenesis protein
Epithelial splicing regulatory protein 1
In DFNB109; hypomorphic mutation affecting alternative splicing in patient-derived induced pluripotent stem cells and other cell-based assays.
Tyrosine-protein phosphatase non-receptor type 3
Impairs sterol 26-hydroxylase activity; confers demethylase activity.
Impairs sterol 26-hydroxylase activity; when associated with A-240 and A-244.
Impairs sterol 26-hydroxylase activity; when associated with A-240 and A-248.
Impairs sterol 26-hydroxylase activity; when associated with A-244 and A-248.
In CTX; impairs sterol 26-hydroxylase activity.
Loss of microtubule-end localization, microtubule plus-end tracking, and decreases MAPRE1 binding; when associated with 369-N--N-370; 503-N-N-504; 590-N-N-591 and 795-N-N-796.
Loss of microtubule-end localization, microtubule plus-end tracking, and decreases MAPRE1 binding; when associated with 369-N-N-370; 458-N-N-459; 503-N-N-504 and 590-N-N-591.
Loss of microtubule-end localization, microtubule plus-end tracking, and decreases MAPRE1 binding; when associated with 369-N-N-370; 458-N-N-459; 503-N-N-504 and 795-N-N-796.
Loss of microtubule-end localization, microtubule plus-end tracking, and decreases MAPRE1 binding; when associated with 369-N-N-370; 458-N-N-459; 590-N-N-591 and 795-N-N-796.
Loss of microtubule-end localization, microtubule plus-end tracking, and decreases MAPRE1 binding; when associated with 458-N--N-459, 503-N-N-504; 590-N-N-591 and 795-N-N-796.
Decreases cellular retinol uptake and impairs retinol storage.
No effect on retinol binding. Abolishes interaction with STA6 and the ability to enhance STA6-mediated vitamin A uptake.
Strongly decreased affinity for retinol. Further decrease in affinity for retinol; when associated with L-109.
Strongly decreased affinity for retinol. Further decrease in for retinol; when associated with L-41.
Ankyrin repeat domain-containing protein 24
Leucine-rich repeat-containing protein 69
U5 small nuclear ribonucleoprotein 40 kDa protein
In SRXY6; increases phosphorylation of the downstream target MAPK3/MAPK1 compared to wild-type and enhances binding of RHOA to the mutant MAP3K1 complex.
In SRXY6; increases phosphorylation of the downstream targets MAPK14 and MAPK3/MAPK1 compared to wild-type and enhances binding of RHOA to the mutant MAP3K1 complex.
Mitogen-activated protein kinase kinase kinase 1
Dynein light chain Tctex-type protein 2B
In CRS5; low-penetrance mutation associated with disease susceptibility; results in gain-of-function.
In GIDID1; reduced interaction with PI4KA.
Found in a family with retinitis pigmentosa.
Voltage-dependent calcium channel gamma-4 subunit
Abolished interaction with PARP2, leading to destabilize the PARP2-nucleosome complex.
Abolished serine ADP-ribosylation by PARP1 and PARP2.
Does not affect serine ADP-ribosylation by PARP1 and PARP2.
Does not affect serine ADP-ribosylation of histones.
Loss of ability to bind PARP1 and histones. Abolishes PARP1 ability to mediate ADP-ribosylation.
Promotes auto-ADP-ribosylation of PARP1.
Promotes auto-ADP-ribosylation of PARP1. Abolished interaction with PARP1.
Strongly reduced serine ADP-ribosylation by PARP1 and PARP2.
Strongly reduced serine ADP-ribosylation by PARP1 and PARP2. Decreases PARP1 ability to mediate tyrosine ADP-ribosylation. Promotes auto-ADP-ribosylation of PARP1.
Induces homodimerization. Reduces adenylate kinase activity by 72% and ATPase activity by 76%. Significantly changes Cajal body organization in the nucleus, resulting in enhanced apoptosis and reduced proliferation.
Cerebral cavernous malformations 2 protein
Cytochrome b5 domain-containing protein 1
DNA-directed RNA polymerase II subunit RPB3
Abolishes the ability to recognize and bind PARsylated proteins.
Loss of iso-ADP-ribose-binding affinity.
Partially suppression of WNT3A signaling and stabilization of AXIN1, TNKS and TNKS2 with or without WNT3A induction. No effect on TNKS1-binding.
Strong decrease in iso-ADP-ribose-binding affinity.
Serine/threonine-protein phosphatase 4 regulatory subunit 1
WAS/WASL-interacting protein family member 1
Abolished homodimerization following interaction with ALKAL1.
Abolishes interaction with PI3-kinase subunit p85, impairs PI3 kinase activity and leads to apoptosis (demonstrated with chimeric EGFR-LTK).
Impairs phosphorylation of CBLC (demonstrated with chimeric EGFR-LTK).
Increases autophosphorylation and interaction with PI3-kinase subunit p85 (demonstrated with chimeric EGFR-LTK).
Loss of interaction with PLCG1, PI3-kinase subunit p85, Ras GTPase-activating protein and RAF1.
May possibly contribute to susceptibility to systemic lupus erythematosus; increases autophosphorylation and interaction with PI3-kinase subunit p85.
Allele ADA*2; found in about 10% of the population; affects duration and intensity of deep sleep; enhances negative effects of sleep loss during sleep deprivation; may have a protective role against male infertility; 20% to 30% decrease in activity.
Decreases enzyme activity by reducing maximum velocity; reduces ADORA1 modulation.
Decreases enzyme activity by reducing maximum velocity; reduces ADORA2A modulation.
Decreases enzyme activity by reducing substrate affinity and maximum velocity.
Decreases enzyme activity by reducing substrate affinity and maximum velocity; abolishes ADORA1 and ADORA2A modulator function.
Decreases enzyme activity by reducing substrate affinity and maximum velocity; reduces ADORA1 and ADORA2A modulation.
In ADASCID; unknown pathological significance; 30% of activity; total loss of activity; when associated with C-97.
In ADASCID; unknown pathological significance; loss of activity on its own; total loss of activity; when associated with V-106.
In an individual with partial ADA deficiency but no immunodeficiency; 1,5% of activity.
In an individual with partial ADA deficiency but no immunodeficiency; 20% of activity.
Moderately reduces enzyme activity; no change in ADORA1 and ADORA2A modulation.
Moderately reduces enzyme activity; reduces ADORA1 and ADORA2A modulation.
No change in enzyme activity; no change in ADORA1 and ADORA2A modulation.
BCL2/adenovirus E1B 19 kDa protein-interacting protein 2
Found in a patient with nephrotic syndrome; unknown pathological significance.
MAPK-interacting and spindle-stabilizing protein-like
N-alpha-acetyltransferase 35, NatC auxiliary subunit
Changed ryanodine-sensitive calcium-release channel activity characterized by increased sensitivity to cytosolic calcium activation.
Decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Changed ryanodine-sensitive calcium-release channel activity. Mutant channels are less resposive to activation by caffeine and store calcium overload. Affects channel sensitivity to cytosolic and luminal calcium activation.
Found in a patient with short-coupled polymorphic ventricular tachycardia at rest; unknown pathological significance; no effect on cytosolic Ca(2+) activation.
In CPVT1; changed ryanodine-sensitive calcium-release channel activity; increased sensitivity to cytosolic calcium activation.
In CPVT1; unknown pathological significance.
In VACRDS; decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; changed ryanodine-sensitive calcium-release channel activity; diminishes the response to activation by luminal Ca(2+) but has little effect on the sensitivity of the channel to activation by cytosolic Ca(2+); shows caffeine-induced Ca(2+) release but exhibits no store-overload-induced Ca(2+) release (SOICR); HL1 cardiac cells transfected with the G-4860 mutant displayed attenuated SOICR activity compared to cells transfected with wild-type RYR2.
In VACRDS; decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; changed ryanodine-sensitive calcium-release channel activity; mutant channels are less resposive to activation by caffeine and store calcium overload; affects channel sensitivity to cytosolic and luminal calcium activation.
Probable disease-associated variant found in a patient with intellectual disability, seizures, short stature and severe atrial arrhythmias.
Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-574 and S-577.
Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-575 and S-577.
Might be implicated in the hereditary spastic paraplegia phenotype.
No loss of interaction with PPIF. Loss of proteolytic activity but no loss of interaction with PPIF; when associated with G-574 and G-575.
Requires 2 nucleotide substitutions; might be implicated in the hereditary spastic paraplegia phenotype.
Abolishes cross-linking. Decreases ERK signaling pathway activation. Abolishes inhibition of EGF receptor degradation after EGF stimulation.
Decreases cross-linking. Abolishes ubiquitination.
Abolishes thyroxine (T4) production; when associated with F-1310, F-2573 and F-2766.
Abolishes thyroxine (T4) production; when associated with F-24, F-1310 and F-2573.
Abolishes thyroxine (T4) production; when associated with F-24, F-1310 and F-2766.
Abolishes thyroxine (T4) production; when associated with F-24, F-2573 and F-2766.
In AITD3; unknown pathological significance.
In TDH3; reduces thyroglobulin synthesis and secretion; promotes thyroglobulin retention within the endoplasmic reticulum.
In TDH3; unknown pathological significance.
Severe loss of thyroxine (T4) production; when associated with F-108, F-2540 and F-2766. Abolishes thyroxine (T4) production; when associated with F-108, F-149, F-2540 and F-2766.
Severe loss of thyroxine (T4) production; when associated with F-108, F-2540 and F-2766. Abolishes thyroxine (T4) production; when associated with F-108, F-234, F-2540 and F-2766.
Severe loss of thyroxine (T4) production; when associated with F-149 or F-234, and F-108 and F-2540. Abolishes thyroxine (T4) production; when associated with F-108, F-149, F-234 and F-2540.
Severe loss of thyroxine (T4) production; when associated with F-149 or F-234, and F-108 and F-2766. Abolishes thyroxine (T4) production; when associated with F-108, F-149, F-234 and F-2766.
Severe loss of thyroxine (T4) production; when associated with F-149 or F-234, and F-2540 and F-2766. Abolishes thyroxine (T4) production; when associated with F-149, F-234, F-2540 and F-2766.
Abolishes ATP-dependent activation of SUMO proteins.
Strongly reduced interaction with UBE2I.
Strongly reduced interaction with UBE2I; when associated with A-235.
Strongly reduced interaction with UBE2I; when associated with A-238.
Strongly reduces ATP-dependent activation of SUMO proteins.
Inactive carboxypeptidase-like protein X2
Abolishes phosphorylation. Reduces COS cell adhesion to ICAM1.
Phosphothreonine; by PKC/PRKCA; in vitro
DEP domain-containing mTOR-interacting protein
17 percent decrease in catalytic activity. No effect on processing.
24 percent decrease in catalytic activity. Slight reduction in processing.
38 percent decrease in catalytic activity. Slight reduction in processing.
Greatly reduced catalytic activity and processing.
Greatly reduced catalytic activity but little effect on processing.
Greatly reduced catalytic activity. No putrescine-stimulated processing.
Loss of activity. Greatly reduced putrescine-stimulated processing.
Loss of activity. Loss of putrescine-stimulated processing.
Loss of activity. Normal putrescine-stimulated processing.
Loss of catalytic activity and processing.
Proton acceptor; for processing activity
S-adenosylmethionine decarboxylase alpha chain
S-adenosylmethionine decarboxylase beta chain
Schiff-base intermediate with substrate; via pyruvic acid
In NPHS12; doesnt affect nuclear envelope localization; doesn't affect nuclear pore complex assembly; doesn't abrogate interaction with NUP205; abrogates SMAD4 interaction; abrogates IPO7 interaction; impairs SMAD4 protein import into nucleus; impairs SMAD4 protein signal transduction.
In NPHS12; doesnt affect nuclear envelope localization; doesn't affect nuclear pore complex assembly; doesn't abrogate interaction with NUP205; abrogates SMAD4 interaction; abrogates IPO7 interaction; impairs SMAD4 protein import; impairs SMAD4 protein signal transduction into nucleus;.
In NPHS12; doesnt affect nuclear envelope localization; impairs nuclear pore complex assembly; doesn't abrogate interaction with NUP205; doesn't affect SMAD4 interaction; doesn't affect IPO7 interaction; impairs SMAD4 protein import into nucleus; impairs SMAD4 protein signal transduction.
ADP-ribosylation factor GTPase-activating protein 1
100,000-fold decrease in catalytic efficiency.
200,000-fold decrease in catalytic efficiency.
800-fold decrease in catalytic efficiency.
In MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis.
In MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis.
Hematopoietically-expressed homeobox protein HHEX
Inhibits APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-339.
Inhibits APC/FZR1 E3 ubiquitin-protein ligase complex activity; when associated with A-374.
Coiled-coil domain-containing protein 148
Enhances protein stability; when associated with A-1032.
Enhances protein stability; when associated with A-1457.
Impairs interaction with ESR1, PPARG, RXRA and THRB. Impairs interaction with THRA; when associated with 648-A-A-649.
Impairs interaction with ESR1, PPARG, THRB and VDR. Impairs interaction with THRA; when associated with 607-A-A-608.
Impairs interaction with ESR2; when associated with A-604; A-607 and A-645.
Impairs interaction with ESR2; when associated with A-604; A-607 and A-648.
Impairs interaction with ESR2; when associated with A-604; A-645 and A-648.
Impairs interaction with ESR2; when associated with A-607; A-645 and A-648.
Increased interaction with PSIP1; when associated with D-886 and D-887.
Increased interaction with PSIP1; when associated with D-887 or D-887 and D-889.
Mediator of RNA polymerase II transcription subunit 1
Phosphomimetic mutant. Increased interaction with PSIP1; when associated with D-886 or D-886 and D-889.
Associated with a significant decrease in urinary kallikrein activity.
Not associated with changes in urinary kallikrein activity.
Trafficking protein particle complex subunit 14
Decrease in 3'-end processing efficiency.
Does not increase its stability at the end of the S phase and through G2 and mitosis.
Increases its stability at the end of the S phase and through G2 and mitosis.
Increases its stability at the end of the S phase and through G2 and mitosis. Active in histone pre-mRNA processing during the G2 phase.
Increases its stability at the end of the S phase and through G2 and mitosis. Inhibits phosphorylation of T-62. Localizes in the nucleus. Reduces interaction with the importin alpha/importin beta receptor. Abolishes interaction with the importin alpha/importin beta receptor; when associated with A-31; A-32; A-33 and A-34 or with A-241; A-242; A-243 and A-244.
Inhibits histone RNA-binding and localization to the cytoplasm.
Reduces interaction with the importin alpha/importin beta receptor. Abolishes interaction with the importin alpha/importin beta receptor; when associated with A-31; A-32; A-33 and A-34 or with A-96; A-97; A-98 and A-99.
Reduces interaction with the importin alpha/importin beta receptor. Abolishes interaction with the importin alpha/importin beta receptor; when associated with A-96; A-97; A-98 and A-99 or with A-241; A-242; A-243 and A-244.
NK1 transcription factor-related protein 2
Zinc finger and BTB domain-containing protein 10
Histone-lysine N-methyltransferase KMT5C
Rap guanine nucleotide exchange factor 6
Small glutamine-rich tetratricopeptide repeat-containing protein beta
Mediator of RNA polymerase II transcription subunit 21
Does not affect transcriptional activity as shown by a transcriptional reporter assay.
In TIDAND and TLIND; severely reduced transcriptional activity as shown by a transcriptional reporter assay.
In TIDTA; decreased transcriptional activity as shown by a transcriptional reporter assay.
In TLIND; unknown pathological significance.
In SPGF11; results in impaired self-association.
Cell cycle checkpoint control protein RAD9B
Dihydroxyacetone phosphate acyltransferase
Probable ATP-dependent RNA helicase DHX35
High frequency in individuals with diabetes mellitus type 2; increased repression activity; increased binding to SIN3A; impairs activation of insulin promoter.
In MODY7; absent in one family member with diabetes; increased repression activity; no alteration in binding affinity to SIN3A.
In MODY7; increased repression activity; no alteration in binding affinity to SIN3A.
Abolishes interaction with EIF4A3, EJC formation and localization in nucleus speckles.
Associated with susceptibility to HVB infection; lower cell surface levels; lower induction of MHC class 1 expression by INF-alpha.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-318; F-337 and F-411. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-318 and F-411. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-411.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-318; F-337 and F-512. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-318 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-512.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316 and F-318.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316; F-411 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-316 and F-337.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-306; F-318 and F-337.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-316; F-318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-316; F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-269; F-316; F-318 and F-337.
Does not inhibit STAT1, STAT2 and STAT3 activation by IFN. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-306; F-316; F-318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and STAT3 activation by IFN; when associated with F-306; F-316; F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and STAT3 activation by IFN; when associated with F-306; F-316; F-318 and F-337.
EF-hand calcium-binding domain-containing protein 4B
Failure to localize to the Golgi membrane.
GDP-binding mutant with reduced GTPase activity and protein stability. Reduced ability to activate JNK signaling pathway. Failure to localize to the microtubule organizing center and Golgi apparatus membrane, instead shows a predominant localization to the cytoplasm.
GTP-binding mutant with reduced GTPase activity but increased protein stability. Increased ability to activate JNK signaling pathway. No effect on its localization to the microtubule organizing center or Golgi apparatus membrane.
GTP/GDP-binding defective mutant with reduced GTPase activity and protein stability. Failure to localize to the microtubule organizing center and Golgi apparatus membrane, instead shows a predominant localization to the cytoplasm.
In EF2MUT; enhanced STIM1 clustering and elevated cytoplasmic Ca2+, thereby causing cell death in T-cells. Loss of calcium-binding. Can rescue JNK phosphorylation when expressed in CRACR2A-depleted T-cells. No effect on its localization to the Golgi membrane.
Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-65 and A-97.
Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-65 and A-99.
Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-63; A-97 and A-99.
Loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with A-65; A-97 and A-99.
In RP58; cannot bind to promoters of retinal-specific genes.
Almost abolishes GPI-GalNAc transferase activity. No effect on Golgi apparatus membrane location.
Glycosylated; when associated with A-87.
Loss of GPI-GalNAc transferase activity.
Loss of glycosylation. Not glycosylated; when associated with N-283. Glycosylated; when associated with N-347.
No effect on GPI-GalNAc transferase activity. No effect on Golgi apparatus membrane location.
Not glycosylated; when associated with A-87.
Post-GPI attachment to proteins factor 4
Reduces GPI-GalNAc transferase activity. No effect on Golgi apparatus membrane location.
Slightly reduces GPI-GalNAc transferase activity. No effect on Golgi apparatus membrane location.
Strongly reduces GPI-GalNAc transferase activity. Accumulates in the endoplasmic reticulum.
Fails to localize at the centromere during interphase.
Loss of kinase activity, autophosphorylation and tumor suppressor activity.
Abolishes enzymatic activity; when associated with A-534.
Abolishes enzymatic activity; when associated with A-536.
Drastic loss of interaction with denatured substrates.
Loss of HSPA5-binding, but no effect on interaction with denatured substrates.
In MRD5; associated with autistic spectrum disorder and epileptic encephalopathy.
In MRD5; associated with autistic spectrum disorder and epileptic encephalopathy; unknown pathological significance.
In MRD5; moderate; associated with autistic spectrum disorder and epileptic encephalopathy.
In MRD5; the disease phenotype consists of intellectual disability and autism; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity.
In MRD5; the disease phenotype consists of intellectual disability, autism and epilepsy; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity.
Probable disease-associated variant found in a patient with West syndrome.
Probable disease-associated variant found in a patient with drug-resistant generalized epilepsy, cognitive impairment and autism spectrum disorder.
Ras/Rap GTPase-activating protein SynGAP
Able to activate mouse MAIT cells (xeno-reactivity).
Associates with B2M and translocates to plasma membrane in the absence of 6-FP. Impairs recognition by pan-cancer TCR, MC.7.G5.
Fails to refold in the presence of 6-FP. Impairs the association with B2M and translocation to the plasma membrane.
Major histocompatibility complex class I-related gene protein
Maestro heat-like repeat-containing protein family member 6
May be involved in congenital central hypoventilation syndrome.
In MTDPS19; no protein detected in patient cells.
Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-471.
Impairs its function as a positive modulator of androgen receptor transactivation; when associated with A-479.
Ubiquitin carboxyl-terminal hydrolase 22
In NNMS; loss of palmitoyltransferase activity; unable to carry out SHH and DHH palmitoylation; does not affect HHAT protein levels.
In NNMS; unknown pathological significance.
In a melanoma cell line; abolishes GTP-binding.
No significant effect on catalytic activity. Defective HHAT-mediated palmitoyl-CoA uptake into microsomal membranes.
Protein-cysteine N-palmitoyltransferase HHAT
Reduced catalytic activity. Defective HHAT-mediated palmitoyl-CoA uptake into microsomal membranes.
FHF complex subunit HOOK interacting protein 2A
Found in a patient with microcephaly severe intellectual disability, ataxia, behavioral abnormalities and speech problems; unknown pathological significance.
Abolished interaction with H2AZ1 and localization to chromatin in response to DNA damage.
Does not affect phosphorylation by PRKDC.
In HLRCC; catalytically inactive mutant; abolished ability to promote DNA repair.
Phosphomimetic mutant; promotes interaction with H2AZ1, leading to increased localization to chromatin in response to DNA damage.
Abolishes CTBP binding but retains transcriptional repressor activity.
Abolishes interaction with CTBP1 and attenuates nuclear hormone receptor-dependent transcription repression.
Disrupts interaction with CTBP1 and CTBP2. Disrupts transcriptional repression; when associated with 442-AS-443.
Disrupts interaction with CTBP1, and CTBP2 to a lesser extent. Disrupts transcriptional repression; when associated with 567-AS-568.
Disrupts interaction with CTBP1. Decreases lysine acetylation. Disrupts nuclear hormone receptor-dependent transcription repression.
Does not disrupt nuclear hormone receptor-dependent transcription repression.
Does not further disrupt transcriptional repression; when associated with 442-AA-443 and 567-AA-568.
Ligand-dependent nuclear receptor binding
Reduces, but does not completely abolish, interaction with CTBP. Reduces transcriptional repression.
ER degradation-enhancing alpha-mannosidase-like protein 1
Normal affinity for misfolded glycoproteins, but impaired SEL1L binding.
1.6 fold decrease in affinity for androstenedione substrate; slightly affects PKA-mediated reduction in catalytic activity as measured in vitro by estrone synthesis from androstenedione (49% decrease compared with 36% for the wild-type protein); no effect on PKG/PRKG1-mediated reduction in catalytic activity in vitro.
2.5 fold decrease in affinity for androstenedione substrate; slightly affects PKA-mediated reduction in catalytic activity as measured by estrone synthesis from androstenedione in vitro (28% decrease compared with 36% for the wild-type protein) and PKG/PRKG1-mediated reduction in catalytic activity in vitro (15% decrease compared with 30% for the wild-type protein).
Found in deaf patients; unknown pathological significance.
In AROD; strongly reduced aromatase activity; 81% reduction of androstenedione metabolism compared to wild-type.
Pancreas transcription factor 1 subunit alpha
Does not affect homodimerization. Abolishes homodimerization but not enzyme activity; when associated with S-39.
Induces a strong decrease in enzyme activity.
Induces migration in both homodimeric and monomeric forms. Abolishes homodimerization but not enzyme activity; when associated with S-12.
Unable to sulfate the sialyl Lewis X tetrasaccharide.
In HYPT1; dominant-negative mutant that perturbs the translational processing from the endoplasmic reticulum to the plasma membrane.
Actin, alpha cardiac muscle 1, intermediate form
In ASD5; reduced affinity for myosin; normal actin filament polymerization ability; normal actomyosin motor function.
Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-52); by Vibrio toxins RtxA and VgrG1
Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1
Does not affect interaction with UBE2L3.
Loss of effect in myelopoiesis. Abolishes interaction with UBE2L3.
Reduced interaction with neddylated CUL5; when associated with 84-A--A-86.
Reduced interaction with neddylated CUL5; when associated with A-100.
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
Does not affect serine protease activity; shows reduced tumor suppressor activity; shows reduced ability to down-regulate phosphatidylethanolamine (PtdEtn) levels.
Serine beta-lactamase-like protein LACTB, mitochondrial
Epidermal growth factor receptor substrate 15
Loss of interaction with STON2 NPF motifs.
Abolishes endoplasmic reticulum localization.
In ASD8; demonstrates only about 75% of the repressive activity of wild-type.
In VSD2; reduces coactivation of the TFAP2C gene to 50% of that obtained with wild-type and represses HIF1A with about 60% efficiency compared to wild-type.
Inhibits transactivation activity; when associated with E-243.
Inhibits transactivation activity; when associated with E-246.
Abolishes production of active form of enzyme.
Loss of palmitoylation by ZDHHC2; when associated with S-129.
Loss of palmitoylation by ZDHHC2; when associated with S-36.
Found in a patient affected by polycystic liver disease; unknown pathological significance.
Found in a patient affected by polycystic liver disease; unknown pathological significance; the patient carried additional PKHD1 variant; the mutation results in significantly reduced alpha-glucosidase activity; dbNP:rs753910059.
Found in a patient with polycystic liver disease; unknown pathological significance.
Found in a patient with polycystic liver disease; unknown pathological significance; no apparent effect on the endoplasmic reticulum localization.
In PKD3; fails to promote PKD1 and PKD2 localization to the cell surface.
In PKD3; unknown pathological significance; no apparent effect on the endoplasmic reticulum localization.
Likely benign variant; no effect on PKD1 and PKD2 localization to the cell surface.
No effect on PKD1 and PKD2 localization to the cell surface.
Thrombospondin type-1 domain-containing protein 7B
Rho guanine nucleotide exchange factor 3
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1
Loss of heparan sulfate-glucosamine N-sulfotransferase activity.
Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1
Impairs the catalytic activity of the helicase.
In NEDBAVC; unknown pathological significance.
In NEDBAVC; unknown pathological significance; requires 2 nucleotide substitutions.
In SRXY11; unknown pathological significance.
Probable ATP-dependent RNA helicase DHX37
Phosphatidylinositol-glycan biosynthesis class X protein
Found in a patient with CHARGE syndrome; unknown pathological significance.
Abolishes creatine efflux activity. Does not affect plasma membrane localization.
Decreases creatine efflux activity. Loss of localization to the plasma membrane.
Decreases in the creatine efflux activity. Does not affect plasma membrane localization.
Does not affect creatine efflux activity.
Does not affect creatine efflux activity. Does not affect plasma membrane localization.
Found in a patient with age-related cataract; unknown pathological significance; decreases creatine transport.
In CTRCT47; loss of localization to the plasma membrane; retained in the endoplasmic reticulum where it undergoes degradation by the proteasome; has no dominant effect on wild-type protein expression and localization.
In GFND2; reduced binding to heparin, endothelial cells and podocytes; impaired capability to induce stress-fiber formation.
In SMDCF; unknown pathological significance.
In isoform 1, isoform 3, isoform 4, isoform 5, isoform 6, isoform 8, isoform 9, isoform 10, isoform 14 and isoform 17.
In isoform 3, isoform 7, isoform 9, isoform 12, isoform 14 and isoform 17.
In isoform 4, isoform 5, isoform 10 and isoform 13.
In isoform 8, isoform 9, isoform 10, isoform 12, isoform 13 and isoform 14.
In isoform 9, isoform 12 and isoform 17.
Little effect on ability to form fibronectin aggregates; when associated with A-642; A-682 and A-684.
Little effect on ability to form fibronectin aggregates; when associated with A-642; A-682 and A-692.
Little effect on ability to form fibronectin aggregates; when associated with A-642; A-684 and A-692.
Little effect on ability to form fibronectin aggregates; when associated with A-682; A-684 and A-692.
Loss of ability to form fibronectin aggregates; when associated with A-695.
Loss of ability to form fibronectin aggregates; when associated with A-697.
No effect on secondary structure nor on fibronectin binding nor on activation of p38 K but abolishes polymerization activity; when associated with A-666.
No effect on secondary structure nor on fibronectin binding nor on activation of p38 kinase but abolishes polymerization activity; when associated with A-663.
Severely compromised ability to form fibronectin aggregates; when associated with A-641 and A-681.
Severely compromised ability to form fibronectin aggregates; when associated with A-641 and A-683.
Severely compromised ability to form fibronectin aggregates; when associated with A-681 and A-683.
Slightly enhanced ability to form fibronectin aggregates; when associated with A-691 and A-694.
Slightly enhanced ability to form fibronectin aggregates; when associated with A-691 and A-696.
Slightly enhanced ability to form fibronectin aggregates; when associated with A-694 and A-696.
tRNA-dihydrouridine(47) synthase [NAD(P)(+)]-like
Ral GTPase-activating protein subunit beta
UDP-xylose and UDP-N-acetylglucosamine transporter
In CMD1S; unknown pathological significance.
In CMH1; associated with phenotype variability.
In CMH1; in cis with M-606 gives a more severe phenotype.
In CMH1; in cis with V-728 gives a more severe phenotype.
In CMH1; unknown pathological significance.
In LVNC5; unknown pathological significance.
Found in a patient with vitelliform macular dystrophy; unknown pathological significance.
In RP91; unknown pathological significance.
In VMD4; unknown pathological significance.
Interphotoreceptor matrix proteoglycan 1
Abolishes Serine/threonine-protein kinase activity.
Abolishes cleavage by caspase-3 and formation of 70 kDa fragment.
Abolishes cleavage by caspase-3 and formation of AF1 fragment.
Abolishes cleavage by caspase-3 and formation of AF3 fragment.
Abolishes interaction with bacterial SspH1.
Decreases interaction with bacterial SspH1.
Substantial reduction of autophosphorylation.
In CLABARS; unknown pathological significance.
Asparagine synthetase [glutamine-hydrolyzing]
In ASNSD; dramatic reduction in protein abundance.
In ASNSD; increases level of protein abundance.
Loss of the glutamine-dependent asparagine synthetase activity, while the ammonia-dependent activity remained unaffected.
SH3 and cysteine-rich domain-containing protein
Abolishes phosphorylation by CK1. No effect on phosphorylation by CK2.
Abolishes phosphorylation by CK2. No effect on phosphorylation by CK1.
In isoform 2, isoform 6, isoform 8 and isoform 9.
Impaired heparin-binding; when associated with N-430 and N-432.
Impaired heparin-binding; when associated with N-430 and N-437.
Impaired heparin-binding; when associated with N-432 and N-437.
In FCHL3; associated with disease susceptibility; has approximately 80% of the specific activity of wild-type enzyme.
In FCHL3; associated with disease susceptibility; loss of activity; frequent mutation.
In HLPP1 and hyperlipidemia; synthesized as a catalytically inactive form; total amount is almost equal to that of the normal enzyme; non-releasable by heparin due to the abnormal structure of the mutant protein.
In HLPP1; Bethesda; loss of activity and abnormal heparin binding.
In HLPP1; almost complete loss of enzyme activity.
In HLPP1; approximately 6% of normal LPL activity and 40% of LPL mass are detected in the patient's postheparin plasma; results in the production of a functionally inactive enzyme.
In HLPP1; complete loss of enzyme activity.
In HLPP1; decreased protein secretion; loss of interaction with GPIHBP1; decreased lipoprotein lipase activity.
In HLPP1; decreases the specific activity of the enzyme; has a mild effect on the secretion of the mutant enzyme; the total LPL mass is reduced compared to that of the wild-type construct.
In HLPP1; decreases the specific activity of the enzyme; reduces the secretion of the mutant protein significantly; the total LPL mass is reduced compared to that of the wild-type construct.
In HLPP1; decreases the specific activity of the enzyme; the total LPL mass is reduced compared to that of the wild-type construct.
In HLPP1; gives rise to a 80% decrease in specific catalytic activity.
In HLPP1; has 48% of normal activity in vitro; decreased levels of activity account for by the lower protein mass levels of the mutants rather than by decreased enzymatic activities; loss of interaction with GPIHBP1.
In HLPP1; has no effect on the specific activity of the enzyme; has a mild effect on the secretion of the mutant enzyme; the total LPL mass is reduced compared to that of the wild-type construct.
In HLPP1; increases the specific activity of the enzyme; has a mild effect on the secretion of the mutant enzyme; the total LPL mass is reduced compared to that of the wild-type construct.
In HLPP1; lacks both triolein and tributyrin esterase activities.
In HLPP1; mild hypertriglyceridemia; partial activity.
In HLPP1; produces an inactive protein which is not secreted into the media.
In HLPP1; results in a moderate reduction in catalytic activity.
In HLPP1; synthesized as a catalytically inactive form.
In HLPP1; the LPL mass level is approximately 67% of the normal; the activity is 32% of the nornal.
Loss of both triglyceride hydrolase and phospholipase activity.
Loss of enzyme activity with triolein and tributyrin.
Loss of interaction with lipoprotein particles, but no effect on interaction with GPIHBP1; when associated with 420-A-A-421.
Loss of interaction with lipoprotein particles, but no effect on interaction with GPIHBP1; when associated with A-417.
Loss of triglyceride hydrolase activity while phospholipase activity remains intact.
Reduced triglyceride hydrolase activity and increased phospholipase activity.
80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-642.
80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-588 and A-751.
80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-318; A-642 and A-751.
80% reduction of insulin-stimulated GLUT4 translocation; when associated with A-588; A-642 and A-751.
Loss of Rab GTPase activation. Only 20% reduction of GLUT4 translocation; even when associated with A-318; A-588; A-642 and A-751.
Inhibits interaction with DLAT. Does not affect pyruvate decarboxylase activity. Loss of multienzyme pyruvate dehydrogenase complex activity.
Pyruvate dehydrogenase E1 component subunit beta, mitochondrial
Reduces interaction with DLAT. Reduces multienzyme pyruvate dehydrogenase complex activity. Does not affect pyruvate decarboxylase activity.
Reduces pyruvate decarboxylase and multienzyme pyruvate dehydrogenase complex activity. Does not affect interaction with DLAT.
Tubulin polyglutamylase complex subunit 2
FERM, ARHGEF and pleckstrin domain-containing protein 2
Cell growth-regulating nucleolar protein
Decreases the production of 28S rRNA and the formation of pre-60S particle.
Reduces copper binding. Reduces copper binding by 75%; when associated with A-31.
Reduces copper binding. Reduces copper binding by 75%; when associated with A-52.
Hematopoietic SH2 domain-containing protein
Loss of the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
No change in the ability to inhibit RE/AP up-regulation in response to TCR/CD28 stimulation.
In isoform A-alpha, isoform A-alpha' and isoform A-beta.
In isoform A-beta, isoform B-beta, isoform C-beta and isoform IB-deltaIX.
In isoform B-alpha, isoform B-beta and isoform 10.
In isoform IA-deltaIX and isoform IB-deltaIX.
Nuclear factor of activated T-cells, cytoplasmic 1
28S ribosomal protein S17, mitochondrial
In a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate.
In a glioma sample; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors.
In a glioma sample; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate.
In colorectal cancer and glioma samples; glioblastoma multiforme; somatic mutation; found in patients with cartilaginous tumors; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate; induces histone methylation; enhances expression of chondrocyte-related genes; disturbs the formation of cartilaginous matrix; inhibits osteogenic differentiation.
Isocitrate dehydrogenase [NADP] cytoplasmic
Associated with H-263 in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS10.
Associated with S-119 in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS10.
In BBS12; significantly reduces the interaction with MKKS; shows significantly decreased interaction with BBS7; the interaction with BBS10 is not affected by this mutation.
In BBS12; unknown pathological significance.
In BBS12; unknown pathological significance; significantly reduces the interaction with MKKS; the interaction with BBS10 is not affected by this mutation.
In a patient with Bardet-Biedl syndrome compound heterozygote for BBS2 mutations; unknown pathological significance.
In a patient with Bardet-Biedl syndrome homozygous for a mutation in BBS2; unknown pathological significance.
Loss of microtubule-binding; when associated with E-259, E-263, E-266 and E-268.
Loss of microtubule-binding; when associated with E-259, E-263, E-266 and E-270.
Loss of microtubule-binding; when associated with E-259, E-263, E-268 and E-270.
Loss of microtubule-binding; when associated with E-259, E-266, E-268 and E-270.
Loss of microtubule-binding; when associated with E-263, E-266, E-268 and E-270.
Abolishes methyltransferase activity, DNA-binding and SAM-binding. Does not abolish transcription activator function.
Abolishes methyltransferase activity. Does not affect SAM-binding, DNA-binding nor transcription activator function.
Dimethyladenosine transferase 1, mitochondrial
Does not affect SAM-binding, DNA-binding nor transcription activator function.
Microfibrillar-associated protein 3-like
Found in a patient with centronuclear myopathy; also identified in a Becker muscular dystrophy patient; unknown pathological significance.
Ubiquitin carboxyl-terminal hydrolase 16
Coiled-coil domain-containing protein 54
Abolishes Cell surface localization without affecting interaction with Latency-associated peptide (LAP) of TGFB1.
Abolishes interaction with Latency-associated peptide (LAP) of TGFB1; when associated with A-211.
Abolishes interaction with Latency-associated peptide (LAP) of TGFB1; when associated with A-350.
Interchain (with C-33 in TGFB1); in linked form
Transforming growth factor beta activator LRRC32
Loss of aconitase activity. Leads to constitutive RNA binding, irrespective of iron levels.
No effect on aconitase activity or on RNA binding.
No effect on iron-regulated RNA binding. Loss of aconitase activity.