SUN domain-containing ossification factor
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.
Coiled-coil domain-containing protein 169
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.
N6-(2-hydroxyisobutyryl)lysine; alternate
N6-(beta-hydroxybutyryl)lysine; alternate
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
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
In a breast cancer sample; somatic mutation.
Putative pre-mRNA-splicing factor ATP-dependent RNA helicase DHX32
In CRSDA; renders the receptor unable to mediate the IL11 signal.
Soluble interleukin-11 receptor subunit alpha
(Microbial infection) ADP-ribosyldiphthamide
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate
In SCA26; compromises the mechanics of translocation.
Strongly reduced phosphorylation at Thr-57.
Found in a patient with spermatogenic failure with radial spoke defects; binding to RSPH3 and calmodulin is abrogated.
IQ and ubiquitin-like domain-containing protein
In a colorectal cancer sample; somatic mutation.
Abolishes interaction with S-adenosyl-L-methionine.
In DYT28; unknown pathological significance.
Abolishes KRIT1 binding; when associated with A-93.
Abolishes KRIT1 binding; when associated with A-96.
Abolishes nuclear import and transcriptional activity.
Reduces KRIT1 binding. No effect on ITGB1 binding.
Stimulates cell spreading on fibronectin to a similar extent as inhibition of CaMKII.
Small nuclear ribonucleoprotein-associated protein N
Lysosome-associated membrane glycoprotein 5
No effect on cell morphology when overexpressed.
May act as a substrate filter by repelling compounds with a negatively charged alpha-carboxylate
O-phosphoseryl-tRNA(Sec) selenium transferase
Inactive peptidyl-prolyl cis-trans isomerase FKBP6
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.
11 X approximate tandem repeats, Ser/Thr-rich
17 X approximate tandem repeats, Ser/Thr-rich
23 X approximate tandem repeats, Ser/Thr-rich
Abolishes oligomerization and significantly increases enzymatic activity.
Critical for end-to-end subunit interaction
In DEE83; the nucleotide substitution also alters the translation of other alternatively spliced products of the gene globally reducing functional enzyme levels and causing reduced synthesis of UDP-glucose and decreased glycogen biosynthetic process; no effect on protein localization; no effect on UTP:glucose-1-phosphate uridylyltransferase activity.
Loss of activity; possibly due to folding defect.
UTP--glucose-1-phosphate uridylyltransferase
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.
Important for activation of transcription
In ECTDS; reduced expression; altered cell morphology; impaired tight junctions; adhesion defects; cytoplasmic translocation.
Loss of activity as transcriptional activator.
Abolishes interaction with ATG8 family proteins and reduces endoplasmic reticulum branching.
Abolishes interaction with ATG8 family proteins.
Abolishes phosphorylation and reduces self-association.
Found in a patient with HSAN2B; uncertain pathological significance; dramatically enhances homooligomerization which results in aberrant endoplasmic reticulum scission and excessive reticulophagy; induces sensory neuron death in vitro.
Phosphomimetic mutant which enhances self-association. Enhanced membrane scission activity; when associated with D-149 and D-151.
Phosphomimetic mutant which enhances self-association. Enhanced membrane scission activity; when associated with D-149 and D-153.
Phosphomimetic mutant which enhances self-association. Enhanced membrane scission activity; when associated with D-151 and D-153.
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.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
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.
In MCPH24; reduced mutant protein levels; impairs assembly of nuclear pore complex as indicated by lower number of nuclear pores in patient fibroblasts.
Serine/threonine-protein phosphatase 4 regulatory subunit 1
Ubiquitin carboxyl-terminal hydrolase 32
Loss of interaction with PIDD1. Decreased PIDDosome assembly. Decreased CASP2 activation.
Loss of interaction with PIDD1. Loss of PIDDosome assembly. Loss of CASP2 activation.
Partial loss of interaction with PIDD1. Decreased PIDDosome assembly. Decreased CASP2 activation.
In MPS6; intermediate form; severe reduction of activity.
In MPS6; mild form; severe reduction of activity.
In MPS6; severe form; low protein levels and activity.
In MPS6; severe form; severe reduction of activity.
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.
In METTL5-3A; abolished methyltransferase activity.
Unknown pathological significance; found in patients with intellectual disability and microcephaly; impaired interaction with TRMT112.
rRNA N6-adenosine-methyltransferase METTL5
RNA binding motif protein, X-linked-like-1
Abolishes enzyme activity with UDP-galactose.
Uridine diphosphate glucose pyrophosphatase NUDT22
Loss of interaction with CCDC8. Decreased affinity for HDAC4.
Probable ATP-dependent RNA helicase DDX20
No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-226 and/or F-257.
No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-226 and/or F-282.
No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-257 and/or F-282.
In DMJDS2; decreased protein abundance; decreased nuclear localization; increased localization to the cytoplasm; changed regulation of gene expression.
In THC6; increased protein tyrosine kinase activity; increased autophosphorylation at Y-419; causes defective megakaryopoiesis associated with increased overall tyrosine phosphorylation in megakaryocytes.
Kinase active. Interacts with PDLIM4; when associated with E-302 and F-419.
Kinase active. Interacts with PDLIM4; when associated with E-307 and F-419.
Kinase inactive. Abolishes ubiquitination promoted by CBLC.
Loss of kinase activity. Loss of interaction with PDLIM4.
Proto-oncogene tyrosine-protein kinase Src
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.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
G protein-activated inward rectifier potassium channel 3
Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium
In ASGD2; complete loss of DNA binding; significant reduction of sequence-specific DNA binding transcription factor activity.
In ASGD2; significant reduction of sequence-specific DNA binding transcription factor activity.
In ASGD2; unknown pathological significance.
In CTRCT34; decreases DNAJB1 expression.
Fails to form damage-dependent nuclear foci or interact with H2AX.
Loss of tyrosine phosphatase activity toward H2AX.
Impairs UBE2S-mediated polyubiquitination, decreasing substrate affinity, does not affect UBE2C-mediated multiubiquitination; when associated with K-350.
Impairs UBE2S-mediated polyubiquitination, decreasing substrate affinity, does not affect UBE2C-mediated multiubiquitination; when associated with K-353.
Chromodomain-helicase-DNA-binding protein 4
In SIHIWES; no effect on interaction with HDAC1; no effect on nuclear localization.
In SIHIWES; unknown pathological significance.
HUWE1-associated protein modifying stress responses 2
Loss of homodimerization. Loss of heterodimerization with HAPSTR1. No effect on interaction with HUWE1.
In a colorectal adenocarcinoma sample; somatic mutation.
Tyrosine-protein kinase transmembrane receptor ROR2
von Willebrand factor A domain-containing protein 5B2
Probable disease-associated variant found in a consanguineous family with intellectual disability.
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
5-methylcytosine rRNA methyltransferase NSUN4
Disrupts complex with MTERFD2; when associated with A-136, R-139 and A-141.
Disrupts complex with MTERFD2; when associated with R-65, A-136 and R-139.
Disrupts complex with MTERFD2; when associated with R-65, A-136, and A-141.
Disrupts complex with MTERFD2; when associated with R-65, R-139 and A-141.
Ankyrin repeat domain-containing protein 26
Loss of helicase activity and DNA mismatch repair function but does not affect the interaction with MCM8, MSH2 or chromatin; when associated with A-358.
Loss of helicase activity and DNA mismatch repair function but does not affect the interaction with MCM8, MSH2 or chromatin; when associated with A-482.
N-acetylserine; in WD40 repeat-containing protein SMU1, N-terminally processed
Required for interaction with IK and with influenza A virus RNA polymerase
WD40 repeat-containing protein SMU1, N-terminally processed
Coiled-coil domain-containing protein 69
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.
Helical; Anchor for type IV membrane protein
Regulator of G-protein signaling 9-binding protein
In EPP1; enzyme retains 12% of activity.
In EPP1; enzyme retains 18% of activity.
In EPP1; enzyme retains 19% of activity.
In EPP1; enzyme retains 37% of activity.
In EPP1; enzyme retains 52% of activity.
In EPP1; enzyme retains 72% of activity.
In EPP1; no detectable enzymatic activity.
In EPP1; unchanged activity; but increased thermolability.
Increases activity inhibition upon interaction with PGRMC1.
In FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coactivator activity; dominant negative effect on nuclear receptors-mediated transcription; increased actin-binding affinity.
In FSGS1; unknown pathological significance.
Rare variant found in patients with IgA nephropathy; unknown pathological significance.
Reduced interaction with RARA. Loss of the transcriptional coac tivator activity toward RARA.
(Microbial infection) N-beta-linked (GlcNAc) arginine
Abolished GlcNAcylation by E.coli NleB1.
Abolishes RIP-mediated NF-Kappa-B activation.
Blocks homodimerization, necroptosis and apoptosis.
In AIEFL; prevents cleavage by CASP8; changed inflammatory response.
In AIEFL; prevents cleavage by CASP8; increased kinase activity; increased inflammatory response.
Phophomimetic mutant. Significant loss of kinase activity.
Phosphoserine; by RIPK3 and autocatalysis
Receptor-interacting serine/threonine-protein kinase 1
Strongly reduced homodimerization and interaction with RIPK3.
Facilitates cleavage of polynucleotide substrates
Important for bactericidal activity, bacterial agglutination activity and binding to bacterial lipopolysaccharide (LPS)
Moderately impairs bactericidal activity, bacterial agglutination activity and binding to bacterial lipopolysaccharide (LPS).
No significant effect on activity towards dinucleotides UpA and CpA. Reduced activity towards polymeric substrates poly(U) and poly(U):poly(A). Significantly reduced activity towards poly(U) and poly(U):poly(A); when associated with A-38.
Significantly reduced activity towards dinucleotides UpA and CpA. Slightly reduced activity towards polymeric substrates poly(U) and poly(U):poly(A). No effect on bactericidal activity. Significantly reduced activity towards poly(U) and poly(U):poly(A); when associated with R-59.
Strongly impairs bactericidal activity, bacterial agglutination activity and binding to bacterial lipopolysaccharide (LPS).
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
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.
Collagen triple helix repeat-containing protein 1
Found in patients with Barrett esophagus.
Ubiquitin-conjugating enzyme E2 variant 3
Abolishes its exchange activity on RHOA.
Reduces exchange activity mediated by GNAQ activation; in truncated construct.
Rho guanine nucleotide exchange factor 25
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1
Asymmetric dimethylarginine; by PRMT1; alternate
Segment polarity protein dishevelled homolog DVL-3
Symmetric dimethylarginine; by PRMT7; alternate
Complement component 1 Q subcomponent-binding protein, mitochondrial
In COXPD33; unknown pathological significance.
Leucine-rich repeat-containing protein 4C
Found in a family with Stocco dos Santos-type X-linked syndromic intellectual developmental disorder; unknown pathological significance.
Found in a patient with Rett syndrome-like phenotype; unknown pathological significance.
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Reduced sumoylation, impaired nuclear localization, but enhanced transcription factor activity.
Abolishes enzyme activity with phosphatidylinositol 3-phosphate. Reduces activity with phosphatidylinositol (3,5)-bisphosphate.
Ribosome biogenesis protein BRX1 homolog
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.
In a lung neuroendocrine carcinoma sample; somatic mutation.
In a metastatic melanoma sample; somatic mutation.
Helical; Signal-anchor for type II membrane protein
Tumor necrosis factor ligand superfamily member 8
AT-rich interactive domain-containing protein 4B
Decreased uridine transport. Normal localization to the cell membrane.
Lower concentrative capacity and altered sodium binding capacity.
Reduced transport of inosine and thymidine.
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
May be associated with susceptibility to monomelic amyotrophy.
ATP-binding cassette sub-family F member 1
Does not inhibit ribosome binding. Reduces ATP-binding. Inhibits ATP-binding and reduces protein synthesis; when associated with M-342. Shows a reduced association with polyribosomes; when associated with M-664. Does not inhibit IRES-mediated protein synthesis; when associated with M-664.
Does not inhibit ribosome binding. Reduces ATP-binding. Inhibits ATP-binding and reduces protein synthesis; when associated with M-664. Shows an enhanced association with polyribosomes; when associated with M-664. Does not inhibit IRES-mediated protein synthesis; when associated with M-664.
Does not inhibit ribosome binding. Reduces protein synthesis; when associated with Q-477.
Does not inhibit ribosome binding. Reduces protein synthesis; when associated with Q-768.
Reduces phosphorylation. Inhibits strongly phosphorylation by CK2; when associated with S-109. Does not inhibits interaction with EIF2; when associated with S-109. Does not inhibit association with ribosomes; when associated with S-109. Reduces EIF2 interaction with ribosomes; when associated with S-109. Does not inhibit protein synthesis; when associated with A-109.
Reduces phosphorylation. Inhibits strongly phosphorylation by CK2; when associated with S-140. Does not inhibit interaction with EIF2; when associated with S-140. Does not inhibit association with ribosomes; when associated with S-140. Reduces EIF2 interaction with ribosomes; when associated with S-140. Does not inhibit protein synthesis; when associated with A-140.
Decreases nuclear import activity of HSPA8. Does not affect the dimer formation. Decreases binding to HSPA8.
Decreases nuclear import activity of HSPA8. Does not affect the dimer formation. Impairs binding to HSPA8.
Decreases nuclear import activity of HSPA8. Does not affect the dimer formation. Markedly decreases binding to HSPA8.
Flexible linker region involved in nuclear import of HSP70 proteins
Increases the nuclear migrating activity.
Required for F-X-F-G repeats-nucleoporins recognition and nuclear import
Connector enhancer of kinase suppressor of ras 2
Inactive serine/threonine-protein kinase PLK5
Ribosome quality control complex subunit TCF25
In MRD11; results in a 50% reduction of interaction of 4.1N protein to GRIA1 compared to wild-type.
Sufficient for binding to RE2 sequence motifs
Necessary for interaction with CBLN3, and homotrimerization
PWWP domain-containing DNA repair factor 3A
O-linked (Xyl...) (glycosaminoglycan) serine
G-protein coupled receptors family 1 profile
Zinc finger and SCAN domain-containing protein 31
4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase 9
Almost complete loss of alpha 1,3-fucosyltransferase activity. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-62. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-101.
Does not affect glycosylation. Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity. Affects subcellular location.
Does not affect glycosylation; when associated with A-3. Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; when associated with A-3. Does not affect subcellular location; when associated with A-3.
Does not affect glycosylation; when associated with A-5. Does not affect 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; when associated with A-5. Does not affect subcellular location; when associated with A-5.
Significantly decrease alpha 1,3-fucosyltransferase activity. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-62. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-153. Loss of catalytic efficiency.
Weakly decreases alpha 1,3-fucosyltransferase activity. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-101. Almost complete loss of alpha 1,3-fucosyltransferase activity; when associated with Q-153. Loss of catalytic efficiency.
In DEE70; loss of interaction with PP1 complex.
In DEE70; severely impaired interaction with actin.
In CSCSC2; enhances binding to microtubules.
Microtubule-associated protein RP/EB family member 2
Abolishes mitochondrial Ca(2+) uptake; when associated with A-185 and A-375.
Abolishes mitochondrial Ca(2+) uptake; when associated with A-185 and A-386.
Abolishes mitochondrial Ca(2+) uptake; when associated with A-375 and A-386.
Has a mild effect on polysaccharides binding.
In allele CLEC18A-1; abolishes binding to polysaccharides.
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9
Decreased ability to interact with and package the SNARESEC22B cargo into COPII vesicles. Has no effect on other cargos packaging.
In AUTSX5; associated with disease susceptibility; no effect on function; rescues embryonic brain development when expressed in a zebrafish heterologous system.
In MRXS35; increased the formation of actively translating ribosomes when expressed in a yeast heterologous system.
In MRXS35; loss of function; fails to rescue embryonic brain development when expressed in a zebrafish heterologous system.
In MRXS35; unknown pathological significance.
Rescues embryonic brain development when expressed in a zebrafish heterologous system.
Does not affect protein folding and binding to UGGT1 or UGGT2.
Telomerase RNA component interacting RNase
Heterogeneous nuclear ribonucleoprotein D0
Loss of in vitro protein phosphatase activity.
No effect on in vitro protein phosphatase activity.
Vacuolar protein sorting-associated protein 29
In MC1DN5; also found in a patient with muscular hypotonia; loss of catalytic activity.
In MC1DN5; unknown pathological significance.
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
In a patient with diffuse leukoencephalopathy with spheroids; unknown pathological significance.
Blocks the inhibition of transcription by RPS6KA5/MSK1.
Polypeptide N-acetylgalactosaminyltransferase 3
Decreased binding to the sequence motif K-D-E-L.
Important for recycling of cargo proteins with the sequence motif K-D-E-L from the Golgi to the endoplasmic reticulum
Inhibits coatomer/ARF-GAP recruitment, receptor redistribution, and intracellular retention of KDEL ligands.
Interaction with the K-D-E-L motif on target proteins
Loss of recycling together with cargo proteins containing the sequence motif K-D-E-L from the Golgi to the endoplasmic reticulum.
Redistribution to the ER is not affected upon PKA inactivation.
(Microbial infection) ADP-ribosylthreonine
Abolishes CteC-catalyzed ADP-ribosylation.
Abolishes HLTF-mediated polyubiquitination of PCNA.
Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)
Loss of DTX3L-mediated polyubiquitination of histone H3 and H4.
No effect on ADP-ribosylation, when associated with K-72.
No effect on ADP-ribosylation, when associated with K-74.
No effect on HLTF-mediated polyubiquitination of PCNA.
Phosphomimetic mutant that binds and activates PRKN.
Prevents phosphorylation in case of mitophagy. Decreased localization of PRKN to mitochondria.
Ankyrin repeat and BTB/POZ domain-containing protein 3
Flexible and important for F-actin binding
In GM1-gangliosidosis; unclassified clinical type.
In GM1G1 and GM1G2; also in a patient with a slowly progressive GM1-gangliosidosis form; 36.2% of wild-type galactosidase activity.
In GM1G1 and GM1G2; decrease in galactosidase activity.
In GM1G1 and GM1G2; loss of galactosidase activity.
In GM1G1 and GM1G2; loss of galactosidase activity; severe mutation.
In GM1G1 and GM1G2; no effect on intrinsic catalytic activity; decreased protein stability; 8.4% of wild-type galactosidase activity; activity severely reduced in transfection with variant F-436.
In GM1G1; 2.1% of wild-type galactosidase activity.
In GM1G1; 2.3% of wild-type galactosidase activity.
In GM1G1; 2.4% of wild-type galactosidase activity.
In GM1G1; 3.4% of wild-type galactosidase activity.
In GM1G1; 4.3% of wild-type galactosidase activity.
In GM1G1; 5.0% of wild-type galactosidase activity.
In GM1G1; complete lack of protein; loss of galactosidase activity.
In GM1G1; decrease in galactosidase activity.
In GM1G1; loss of galactosidase activity.
In GM1G1; loss of galactosidase activity; severe mutation.
In GM1G1; loss of galactosidase activity; severe mutation; causes a rapid degradation of the protein precursor.
In GM1G1; mild phenotype; unknown pathological significance; reduction of galactosidase activity.
In GM1G1; unknown pathological significance.
In GM1G1; with cardiac involvement in some patients; loss of galactosidase activity; severe mutation.
In GM1G1; with cardiac involvement in some patients; loss of galactosidase activity; severe mutation; causes a rapid degradation of the protein precursor.
In GM1G2 and GM1G1; loss of galactosidase activity.
In GM1G2 and GM1G3; 6.7% of wild-type galactosidase activity.
In GM1G2; 3.0% of wild-type galactosidase activity; the mutant protein is localized in the lysosomal-endosomal compartment.
In GM1G2; 7.4% of wild-type galactosidase activity.
In GM1G2; decrease in galactosidase activity.
In GM1G2; unknown pathological significance.
In GM1G3 and MPS4B; mild form; 5.7% of wild-type galactosidase activity.
In GM1G3; decrease in galactosidase activity.
In GM1G3; no effect on catalytic activity; decreased protein stability.
In GM1G3; originally classified as Morquio syndrome.
In MPS4B and GM1G1; severe decrease in galactosidase activity.
In MPS4B; 1.1% of wild-type galactosidase activity.
In MPS4B; 17.4% of wild-type galactosidase activity.
In MPS4B; 2-5% of wild-type galactosidase activity.
In MPS4B; 2.0% of wild-type galactosidase activity.
In MPS4B; 24.0% of wild-type galactosidase activity.
In MPS4B; also in a patient with a slowly progressive form of GM1-gangliosidosis; loss of galactosidase activity.
In MPS4B; decrease in galactosidase activity.
In MPS4B; decreased galactosidase activity.
In MPS4B; loss of galactosidase activity.
In MPS4B; mild form; 2.1% of wild-type galactosidase activity.
In MPS4B; mild form; fibroblasts from MPS4B compound heterozygotes for K-484 and A-500 have 1.9% of wild-type galactosidase activity.
Results in near-normal activity corresponding to 60%-100% of the wild-type depending on the expression system.
Seems to have a modulating action in the expression of the severity of other mutations.
T-cell receptor gamma alternate reading frame protein
Probable E3 ubiquitin-protein ligase makorin-3
Required for interaction with CBX5 and TBPL1
Coiled-coil domain-containing protein 30
Coiled-coil domain-containing protein 38
Abolishes SH3BP5-mediated guanine nucleotide exchange.
Constitutively active mutant. Decreases GTPase activity. Disrupts the trafficking of CDH1 to the plasma membrane and promotes accumulation of CDH1 in RAB11A endosomes in nonpolarized cells. Promotes mistargeting of CDH1 to the apical membrane in polarized cells.
Decreases SH3BP5-mediated guanine nucleotide exchange.
Dominant-negative mutant. Induces increased number of binucleated cells, indicating defects in cytokinesis. Inhibits the transport of NPC1L1 to the plama membrane. Disrupts the trafficking of CDH1 to the plasma membrane and promotes accumulation of CDH1 in RAB11A endosomes in nonpolarized cells. Promotes mistargeting of CDH1 to the apical membrane in polarized cells. Increased interaction with ATP9A. Loss of interaction with WDR44, decreased WDR44-positive tubules and loss of E-cadherin export.
Impairs protein folding and decreases affinity for guanine nucleotides.
Mildly decreases SH3BP5-mediated guanine nucleotide exchange.
Nearly abolishes SH3BP5-mediated guanine nucleotide exchange.
In IMD80; cell cycle defect and replication stress in patient-derived cells; loss of nuclear localization.
In IMD80; no effect on the formation of the replisome.
dolichyl-phosphate-mannose--protein mannosyltransferase
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.
Magnesium transporter MRS2 homolog, mitochondrial
Doublesex- and mab-3-related transcription factor 2
Phosphomimetic mutant; enhances kinase activity.
Abolishes cleavage into active form; when associated with A-247.
Abolishes cleavage into active form; when associated with A-249.
Platelet-derived growth factor D, latent form
Platelet-derived growth factor D, receptor-binding form
A disintegrin and metalloproteinase with thrombospondin motifs 20
Breakpoint for insertion to form PDE4DIP-PDGFRB fusion protein
In isoform 9, isoform 10 and isoform 12.
Does not restore GAP activity in yeast complementation assay.
Late secretory pathway protein AVL9 homolog
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with A-702; A-709; A-711 and A-712.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with A-702; A-709; A-711 and A-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with A-702; A-709; A-712 and A-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with A-702; A-711; A-712 and A-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with A-709; A-711; A-712 and A-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with D-702; D-709; D-711 and D-712.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with D-702; D-709; D-711 and D-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with D-702; D-709; D-712 and D-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with D-702; D-711; D-712 and D-714.
Abolishes SLC9A5 phosphorylation by CSNK2A1 and abolishes CSNK2A1-mediated binding of ARRB2; when associated with D-709; D-711; D-712 and D-714.
Does not disrupt the binding of ARRB2. Does not affect endocytosis of SLC9A5.
Does not disrupt the binding of ARRB2. Impaired endocytosis of SLC9A5.
Cyclic AMP-dependent transcription factor ATF-6 beta
Processed cyclic AMP-dependent transcription factor ATF-6 beta
Katanin p60 ATPase-containing subunit A-like 2
Eukaryotic peptide chain release factor subunit 1
In AAQ mutant; abolished ability to mediate translation termination. Can recognize stop codons in ribosomal A-site, but is unable to catalyze peptidyl-tRNA hydrolysis, promoting ribosome collisions.
NIKS motif; plays an important role in translational termination
Loss of PLA2 activity toward PAF. Impairs anti-adenoviral activity.
115-fold more potently inhibited by the alpha-conotoxin ImI; but no change in inhibition by the alpha-conotoxin ImII.
Essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to cell membrane
Neuronal acetylcholine receptor subunit alpha-7
Neurotransmitter-gated ion-channel ligand-binding
Neurotransmitter-gated ion-channel transmembrane
GTP cyclohydrolase 1 feedback regulatory protein
Ciliary neurotrophic factor receptor subunit alpha
Small integral membrane protein 10-like protein 2A
Small integral membrane protein 10-like protein 2B
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 2
In HJDD; due to a nucleotide substitution that affects a canonical splice site; patient cells contain normally spliced transcripts corresponding to protein variant T-355 but also transcripts lacking exon 5 and corresponding to protein variant 271-L--A-355 del.
In HJDD; due to a nucleotide substitution that affects a canonical splice site; patient cells contain transcripts lacking exon 5 and corresponding to protein variant 271-L--A-355 del but also normally spliced transcripts corresponding to protein variant T-355; loss of ferroxidase 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
Zinc finger SWIM domain-containing protein 8
In MCOPS16; does not affect nuclear localization; reduces DNA binding activity.
In MCOPS16; unknown pathological significance.
Tectonin beta-propeller repeat-containing protein 2
Abolished ubiquitination by the SCF(FBXL17) complex.
Abolishes DNA-binding and transcriptional repression activity, no effect on nuclear localization and interaction with HDAC5.
Abolishes DNA-binding and transcriptional repression activity, perturbs nuclear localization. No effect on interaction with HDAC5.
Abolishes acetylation. No effect on interaction with MTA3, NCOR1 and NCOR2.
Abolishes interaction with HDAC2 and MTA3 as well as transcriptional repressor and transforming activities. Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with K-21 and A-116.
Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with A-116 and 376-Q--Q-379.
Abolishes interaction with NCOR2 and HDAC2, no effect on interaction with CTBP1 and transcriptional autoinhibition; when associated with K-21 and 376-Q--Q-379.
No effect on DNA-binding, nuclear localization, transcriptional repression activity and interaction with HDAC5.
Required for interaction with NuRD complex and for transcriptional repressor activity
Found in a renal cell carcinoma sample; somatic mutation.
No significant effect on inhibition of elastase, trypsin and chymotrypsin.
Reactive bond for chymotrypsin, trypsin and elastase
Reduced inhibition of elastase. Strongly reduced inhibition of chymotrypsin and trypsin.
Strongly reduced inhibition of elastase. Abolishes inhibition of trypsin.
DNA-directed RNA polymerase III subunit RPC8
Meiosis-specific coiled-coil domain-containing protein MEIOC
Cilia- and flagella-associated protein 45
In HTX11; loss of panaxonemal expression in respiratory cilia and in sperm flagella.
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 adenocarcinoma sample; somatic mutation.
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.
In HLD5; induces misfolding and degradation, leading to destabilization of the PI4K complex.
No binding to IP4 and loss of plasma membrane localization.
Ribonucleases P/MRP protein subunit POP1
In GLCC; unknown pathological significance.
May be associated with increased risk for prostate cancer; results in decreased affinity for laminin.
Non-collagenous domain 1 association domain
O-linked (Xyl...) (chondroitin sulfate) serine
Zinc finger and BTB domain-containing protein 2
In DFNA79; unknown pathological significance.
Abolishes cleavage and production of vasculostatin-120.
Abolishes processing of vasculostatin-40.
Does not affect processing of vasculostatin-40.
Increased levels of vasculostatin-120 and decreased levels of vasculostatin-40.
Indispensable for interaction with MAGI1
N-terminal stalk following vasculostatin-120 cleavage which is not required for signaling activity
Beta-crystallin A3, isoform A1, Delta4 form
Beta-crystallin A3, isoform A1, Delta7 form
Beta-crystallin A3, isoform A1, Delta8 form
In FFEVF3; unknown pathological significance.
In CTRCT12; unknown pathological significance.
Tubulin polymerization-promoting protein family member 3
Probable tRNA (uracil-O(2)-)-methyltransferase
In LGMDR3; associated with P-G-A-Q-P-136 ins.
Found in a patient with cerebellar ataxia intellectual disability and dysequilibrium syndrome; unknown pathological significance; no effect on protein folding; no effect on tubulin heterodimer formation; no effect on integration into the microtubule lattice; no effect on cytoskeleton subcellular location.
In CDCBM7; affects microtubules assembly.
In CDCBM7; decreased protein expression; decreased tubulin heterodimer formation; no effect on integration into the microtubule lattice; no effect on microtubule cytoskeleton subcellular location; loss of axon guidance.
In CDCBM7; decreased tubulin heterodimer formation; decreased ability to incorporate into the cytoskeleton; no effect on microtubules disintegration; increased ability to repolymerize.
Abolishes interaction with GPSM2 and GPSM1; when associated with R-89.
In isoform 2, isoform 4, isoform 5 and isoform 6.
Strongly reduces interaction with GPSM2. Abolishes interaction with GPSM2 and GPSM1; when associated with D-97.
Lysophosphatidylcholine acyltransferase 2
Found in two consanguineous families with intellectual disability; unknown pathological significance.
Protein phosphatase 1 regulatory subunit 14B
8-fold increase in MMA production and almost complete elimination of sDMA production.
Loss of interaction with SF3B2; Abolishes enzymatic activity.
EP300-interacting inhibitor of differentiation 3
Non-structural maintenance of chromosome element 4 C-terminal
Inverted topology. No effect on activity.
No effect on topology. Increased Km for corticosterone.
Predominantly inverted topology. No effect on activity.
Coiled-coil domain-containing glutamate-rich protein 1
F-box and leucine-rich repeat protein 13
Decreases interaction with RHOA. Decreases stimulation of RHOAGTPase activity.
Decreases interaction with RHOA. Strongly decreases stimulation of RHOAGTPase activity.
Strongly decreases interaction with RHOA. Strongly decreases stimulation of RHOAGTPase activity.
In MCPH10; hypomorphic mutation; may cause altered transcript but some full-length protein is still formed.
Abolished localization to the nucleus. Abolished tyrosine--tRNA ligase activity. Abolished ability to activate PARP1.
Found in a patient with hereditary motor and sensory neuropathy; unknown pathological significance.
Found in a patient with proximal-predominant motor neuropathy; probable disease-associated variant; loss of function.
In IMNEPD2; hypomorphic variant in yeast complementation assays; decreased homodimerization; does not affect localization to the cytoplasm.
In IMNEPD2; unknown pathological significance.
N-acetylglycine; in Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed
Slightly reduced tyrosine--tRNA ligase activity.
Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed
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.
N-linked (GlcNAc...) (complex) asparagine
Inactive cell surface hyaluronidase CEMIP2
ATP-binding cassette sub-family C member 10
Testis-specific chromodomain protein Y 1
Abolishes secretion. No effect on multimer formation.
No effect on secretion. Affects multimer formation.
Myosin light chain kinase 2, skeletal/cardiac muscle
Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus.
In FASPS2; strongly reduces kinase activity.
In breast cancer samples; infiltrating ductal carcinoma; somatic mutation.
ADP-ribosylation factor GTPase-activating protein 1
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 MC1DN1; loss of mitochondrial respiratory complex I; altered nonsense mediated mRNA decay.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial
Probable phospholipid-transporting ATPase IM
Heparan sulfate glucosamine 3-O-sulfotransferase 1
Deamidated asparagine; partial; alternate
Abolishes localization to cytoplasmic vesicles in case of infection by S.typhimurium.
Critical for binding to sialylated and sulfated oligosaccharides
Does not affect localization to cytoplasmic vesicles in case of infection by S.typhimurium.
Impaired formation of the CRL2(PRAME) complex.
Loss of interaction with RARA and defective in repressing RARA signaling.
Melanoma antigen preferentially expressed in tumors
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.
Reversion-inducing cysteine-rich protein with Kazal motifs
Abolishes the inhibitory effect against ligand-induced activation of PLCG2 by CLEC1B and GP6:FCER1G; when associated with F-237.
In THAMY; increased protein degradation; decreased enhancement of hematopoietic lineage differentiation.
Loss of tyrosine phosphorylation and loss of interaction with PTPN6 and PTPN11.
Megakaryocyte and platelet inhibitory receptor G6b
Reduced level of tyrosine phosphorylation and interaction with PTPN6 and PTPN11.
Signal recognition particle 19 kDa protein
Cyclic AMP-responsive element-binding protein 3-like protein 2
Processed cyclic AMP-responsive element-binding protein 3-like protein 2
Decreased kinase activity. Reduced binding of S100B.
In a aLLTEL/AML1+ sample; somatic mutation.
Loss of autophosphorylation and kinase activity.
In HSN1E; unstable protein with decreased enzymatic activity and impaired heterochromatin binding ability after the S phase.
Interaction with the PRC2/EED-EZH2 complex
Loss of interaction with L3MBTL3 and DCAF5. Loss of ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex.
Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-667.
Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-664 and G-670.
Reduces activity about 10-fold; when associated with G-653; G-656; G-659; G-667 and G-670.
Reduces activity about 10-fold; when associated with G-653; G-656; G-664; G-667 and G-670.
Reduces activity about 10-fold; when associated with G-653; G-659; G-664; G-667 and G-670.
Reduces activity about 10-fold; when associated with G-656; G-659; G-664; G-667 and G-670.
Bromodomain and WD repeat-containing protein 1
HIG1 domain family member 1A, mitochondrial
Bridge-like lipid transfer protein family member 3A
Interchain (with C-60 in C8-gamma chain)
In Bonheiden; causes severe hereditary hemolytic anemia.
In TNCY; hemoglobin F-Brugine/Feldkirch; lowered affinity for oxygen.
In TNCY; hemoglobin Osaka; the presence of a tyrosine causes the formation of a covalent link with heme iron, so that the iron is stabilized in the ferric form; when this occurs methemoglobin is formed, oxygen can no longer bind to heme and cyanosis occurs.
In TNCY; hemoglobin Toms River; the side chain of methionine decreases both the affinity of oxygen for binding to the mutant hemoglobin subunit via steric hindrance and the rate at which it does so; the mutant methionine is converted to aspartic acid post-translationally.
Xylosyl- and glucuronyltransferase LARGE2
Cholesterol side-chain cleavage enzyme, mitochondrial
Ubiquitin carboxyl-terminal hydrolase 17-like protein 10
Abolished GTPase activation (GAP) activity.
Does not assemble into a stable folliculin complex (LFC), preventing localization to the lysosomal membrane upon amino acid starvation.
Essential for GTPase activation (GAP) activity
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.
In NEM7; protein is less soluble when expressed in Escherichia coli.
In NEM7; unknown pathological significance.
Abolishes interaction with CD2AP and CIN85/SH3KBP1.
Interaction with TSG101, VPS37B and VPS28
Mimics constitutively phosphorylated form and has the ability to interact with CD2AP and CIN85/SH3KBP1 without EGF treatment.
Aminoacyl-transfer RNA synthetases class-II family profile
In SIMHA; unknown pathological significance.
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.
Nucleoporin Nup133/Nup155-like C-terminal
Nucleoporin Nup133/Nup155-like N-terminal
57% reduction in mRNA export activity and loss of nuclear rim staining.
In PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density and impaired channel inactivation.
In PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density.
In SANDD; the mutant channels are unable to conduct calcium ions currents and have abnormal voltage-dependent gating.
Probable disease-associated variant found in a patient with autism spectrum disorder; gain of function; increases channel activity; the mutant channel is activated at less depolarized potentials with an increased current density and impaired channel inactivation.
Voltage-dependent L-type calcium channel subunit alpha-1D
Voltage-dependent calcium channel alpha-1 subunit IQ
No arylsulfatase activity in the media of retinal epithelium cell.
Sufficient for E3 SUMO-protein ligase activity
Leucine-rich repeat and calponin homology domain-containing 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 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.
Part of a helix bundle domain, formed by helices from N-terminal and C-terminal regions
Abolishes enzyme activity. Abolishes interaction with PLCG.
Abolishes proteolytic cleavage by PSEN1.
In a bladder transitional cell carcinoma sample; somatic mutation.
In a glioma low grade oligodendroglioma sample; somatic mutation.
Loss of phosphorylation site. Abolishes interaction with CBL.
Loss of phosphorylation site. Abolishes interaction with PIK3R1.
Loss of phosphorylation site. Abolishes interaction with PLCG.
Reduces phosphorylation at other tyrosine residues.
Strongly increases kinase activity. Increases activity in promoting proliferation of endothelial cells.
Vascular endothelial growth factor receptor 1
Risk factor for T2D when associated with G-127, S-340 and T-443; reduced pyruvate transmembrane transporter activity, loss of interaction with BSG and decreased localization to plasma membrane when associated with G-127, S-340 and T-443.
Risk factor for T2D when associated with I-113, G-127 and S-340; reduced pyruvate transmembrane transporter activity, loss of interaction with BSG and decreased localization to plasma membrane when associated with I-113, G-127 and S-340.
Risk factor for T2D when associated with I-113, G-127 and T-443; reduced pyruvate transmembrane transporter activity, loss of interaction with BSG and decreased localization to plasma membrane when associated with I-113, G-127 and T-443.
Risk factor for T2D when associated with I-113, S-340 and T-443; reduced pyruvate transmembrane transporter activity, loss of interaction with BSG and decreased localization to plasma membrane when associated with I-113, S-340 and T-443.
EF-hand calcium-binding domain-containing protein 13
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
In COXPD19; can form a normal complex with NFS1 but the desulfurase enzymatic activity of this complex is severely decreased compared to control.
In NS11; constitutively active form; increased GTPase activity.
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.
Sufficient for GEF activity towards RAB21
Suppressor APC domain-containing protein 1
Loss of proteolytic processing in response to low sterol.
No effect on proteolytic processing in response to low sterol.
Processed sterol regulatory element-binding protein 2
Restores cleavage by S2P; when associated with F-495 and L-496. No effect on site of cleavage by S2P.
Sterol regulatory element-binding protein 2
In BJS; with mild mitochondrial complex III deficiency.
In MC3DN1 and BJS; with mild mitochondrial complex III deficiency; causes a decreased incorporation of the Rieske iron-sulfur protein UQCRFS1 into complex III.
In MC3DN1; abolishes interaction with LETM1.
In MC3DN1; causes a decreased incorporation of the Rieske iron-sulfur protein UQCRFS1 into complex III.
Does not inhibit dipeptidyl peptidase activity, interaction with ADA and homodimer formation.
Inhibits strongly homodimerization, dipeptidyl peptidase activity, interaction with CARD11 and T-cell costimulation activity.
Inhibits weakly homodimerization and dipeptidyl peptidase activity.
Associated with variability of hair, eye and skin pigmentation; in Caucasians associated with dark hair, skin and eye color; strong protective effect for melanoma risk.
Associated with variability of hair, eye and skin pigmentation; in Caucasians associated with dark hair, skin and eye color; strong protective effect for melanoma risk; decreased protein stability; no effect on subcellular location.
Heterogeneous nuclear ribonucleoprotein H3
FAD-dependent oxidoreductase domain-containing protein 1
In MC1DN19; hypomorphic variant in vitro.
No effect. Able to restore complex I assembly when expressed in cells lacking FOXRED1.
Not able to restore complex I assembly when expressed in cells lacking FOXRED1.
Associated with susceptibility to drug abuse; the mutant enzyme is more sensitive to proteolytic degradation; displays reduced cellular expression probably due to a post-translational mechanism preceding productive folding.
In LGMDR27; unknown pathological significance.
Essential for its interaction with RNA polymerase II, transcription-coupled nucleotide excision repair activity, association with chromatin after UV irradiation and for mediating the UV-induced translocation of ERRC8 to the nuclear matrix
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.
N-terminal domain; essential for its chromatin remodeling activity
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.
PiggyBac transposable element-derived protein
In PFBMFT6; results in shortened telomeres and impaired hematopoiesis when expressed in iPSC-derived hematopoietic cells; increased single-stranded DNA binding; increased telomeric DNA binding; has no effect on the formation of canonical replication protein A complex.
In PFBMFT6; unknown pathological significance; has DNA-binding properties similar to the wild-type; has no effect on the formation of canonical replication protein A complex.
In PFBMFT6; unknown pathological significance; increased single-stranded DNA binding; increased telomeric DNA binding; has no effect on the formation of canonical replication protein A complex.
Loss of HELB-binding; when associated with E-41.
Loss of HELB-binding; when associated with E-43.
Loss of function in DNA replication and mismatch repair without effect on DNA-binding activity; when associated with S-500.
Loss of function in DNA replication and mismatch repair without effect on DNA-binding activity; when associated with S-503.
Replication protein A 70 kDa DNA-binding subunit
Replication protein A 70 kDa DNA-binding subunit, N-terminally processed
Significant reduction of sumoylation. Loss of sumoylation; when associated with R-577.
Slight sumoylation decrease. Loss of sumoylation; when associated with R-449.
In MRXSPM; unknown pathological significance; reduced sulfotransferase activity; no effect on protein levels.
In HMN9; decreased tryptophan-tRNA ligase activity; dominant negative effect; decreased general protein synthesis; decreased cell viability; no effect on homodimerization.
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.
Coiled-coil domain-containing protein 57
Microtubule-associated proteins 1A/1B light chain 3 beta 2
Phosphatidylethanolamine amidated glycine; alternate
Phosphatidylserine amidated glycine; alternate
In CCDS2; retains no significant activity.
Binding site for the uncoating ATPase, involved in lattice disassembly
Involved in binding clathrin light chain
In MC1DN34; unknown pathological significance.
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 8
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.
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.
Coiled-coil domain-containing protein 88B
May be a susceptibility factor for developing esophageal cancer especially in smoking population.
In CHTE; impairs IGSF1 trafficking to the plasma membrane.
Abrogates APP cleavage. Reduces Notch signaling. Loss of proteolytic activity.
Disintegrin and metalloproteinase domain-containing protein 10
In AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced amyloid-beta plaque load and reactive gliosis.
In a cutaneous metastatic melanoma sample; somatic mutation.
Abolished histone deacetylase and decrotonylase activities.
Abolishes histone deacetylase and decrotonylase activities.
Abolishes interaction with CHFR; when associated with I-297.
Abolishes interaction with CHFR; when associated with Y-287.
Decreases deacetylase activity, and disrupts interaction with NuRD and SIN3 complexes.
Impaired protein deacetylase activity without affecting the protein decrotonylase activity.
No effect on deacetylase activity, no effect on interaction with NuRD and SIN3 complexes.
Slightly decreases deacetylase activity, no effect on interaction with NuRD and SIN3 complexes.
Slightly decreases deacetylase activity.
Strongly decreases deacetylase activity, and disrupts interaction with NuRD and SIN3 complexes.
17-beta-hydroxysteroid dehydrogenase type 6
In LGMDR23; decreased protein abundance in patient cells.
In MDC1A; unknown pathological significance.
Decreased nuclear localization when associated with 218-A--A-220. Complete loss of nuclear localization; when associated with 85-A-A-86 and 218-A--A-220.
Decreased nuclear localization. Complete loss of nuclear localization; when associated with 218-A--A-220 and 230-A--A-232.
Decreased nuclear localization; when associated with 230-A--A-232. Complete loss of nuclear localization; when associated with 85-A-A-86 and 230-A--A-232.
Decreases 60S ribosomes synthesis. Strongly decreases 60S ribosomal subunit synthesis, enhances interaction with WDR74 and increases association of WDR74 and MTREX as well as induces partial migration of WDR74 to the nucleoplasm; when associated with Q-365.
Decreases 60S ribosomes synthesis. Strongly decreases 60S ribosomal subunit synthesis, enhances interaction with WDR74 and increases association of WDR74 and MTREX as well as induces partial migration of WDR74 to the nucleoplasm; when associated with Q-682.
Loss of ATP-binding. No effect on interaction with TERT, MTREX and RPL5 and on telomerase activity. Significant reduction in the level of the 60S ribosomal subunit.
Loss of ATP-binding. Significant reduction in interaction with TERT and in telomerase activity. Loss of interaction with MTREX.
Loss of nucleolar localization and interaction with RPL5.
Disrupts chloride ion dependence of serotonin transport. Results in larger serotonin-induced currents independent of the chloride ion gradient. Increases serotonin transport rate; when associated with C-336. Decreases expression at the cell surface.
Found in 15 autistic individuals, decreased expression at the cell surface; increased affinity for serotonin; increased serotonin transport capacity; loss of regulation through cGMP and MAP kinases pathways; hypoplasia of the enteric nervous system and decreased gastrointestinal peristaltic reflexes shown by a mouse knockin model of the mutation.
Found in 2 autistic individuals; increased affinity for serotonin; increased serotonin transport rate.
Found in 2 autistic individuals; increased expression at the cell surface; increased affinity for serotonin.
Impairs serotonin transport. Results in chloride ion-independent serotonin transport; when associated with A-101 or C-101.
Linked with susceptibility to obsessive-compulsive disorder; increased serotonin transport capacity.
Sodium:neurotransmitter symporter serotonin N-terminal
Abolishes binding to TNRFSF6 and cytotoxicity.
In ALPS1B; significant reduction in cytotoxicity and apoptosis and inhibition of the shedding of the soluble form.
Lowers binding to TNFRSF6 and abolishes cytotoxicity.
Lowers binding to TNFRSF6 and reduces cytotoxicity more than 100-fold.
Tumor necrosis factor ligand superfamily member 6, membrane form
Tumor necrosis factor ligand superfamily member 6, soluble form
In IMD32A; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA.
In IMD32B; in resting macrophages, no effect on cytoplasmic subcellular localization; loss of nuclear subcellular localization upon IFN-gamma induction; decreased protein abundance; increased proteasome-dependent degradation; increased ubiquitination and sumoylation; loss of transcriptional repressor activity; loss of IRF1-dependent transcriptional repressor activity; loss of IRF1-dependent transcriptional activator activity; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA.
In resting macrophages, no effect on cytoplasmic subcellular localization. Decreased nuclear subcellular localization upon IFN-gamma induction. Partial loss of IRF1-dependent transcriptional activator activity.
In resting macrophages, no effect on cytoplasmic subcellular localization. Loss of nuclear subcellular localization upon IFN-gamma induction. Loss of IRF1-dependent transcriptional activator activity.
In resting macrophages, no effect on cytoplasmic subcellular localization. No effect on nuclear subcellular localization upon IFN-gamma induction. No effect on transcriptional activator activity. No effect on IRF1-dependent transcriptional activator activity.
In CCDD; the mutation results in decreased protein solubility; causes abnormal aggregation; markedly reduced protein expression is observed in the sarcoplasm and nuclei of patient cardiomyocytes.
In a head & Neck squamous cell carcinoma sample; somatic mutation.
DnaJ homolog subfamily C member 30, mitochondrial
In LHONAR; results in reduced turnover of N-module subunits of the respiratory chain complex I and reduced complex I activity in homozygous patient-derived cells.
Abolishes ubiquitination. No effect on interaction with SHPRH.
Alters chromatin-associated PCNA stability and its function in DNA replication and repair.
Complete loss of interaction with UHRF2.
In ATLD2; a hypomorphic mutation affecting DNA repair in response to UV; results in significantly decreased interaction with FEN1, LIG1 and ERCC5.
Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-20 and R-77.
Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-20 and R-80.
Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-14; R-77 and R-80.
Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-13; R-20; R-77 and R-80.
Inhibits acetylation, recruitment to DNA damage sites, inducible ubiquitination and protein degradation, DNA replication and repair synthesis efficiencies, but homotrimer formation, nuclear recruitment to DNA damage sites, interactions with CREBBP, EP300 and POLD1 are similar as the wild-type; in association with R-14; R-20; R-77 and R-80.
Inhibits recruitment to DNA damage sites, but nuclear localization is similar as the wild-type; in association with A-77.
Inhibits recruitment to DNA damage sites, but nuclear localization is similar as the wild-type; in association with A-80.
No effect on POLD3-binding. Impairs binding to ALKBH2.
No effect on POLD3-binding. No effect on ALKBH2-binding.
Strong decrease in POLD3-binding. Impairs binding to ALKBH2.
15 X 5 AA repeats of C-C-[RQVGE]-[SPTN]-[TASPF]
CCR4-NOT transcription complex subunit 2
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.
Probable ubiquitin carboxyl-terminal hydrolase FAF-Y
Pleckstrin homology domain-containing family H member 2
In a patient with amyotrophic lateral sclerosis.
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.
Almost no change in KM and Vmax for MgATP and R-MVP.
Approximately 10-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and 50-fold increase in KM for R-MVP.
Approximately 100000-fold decrease in Vmax for MgATP.
Approximately 1400-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and R-MVP.
Approximately 15-fold decrease in Vmax for MgATP and R-MVP. Approximately 50-fold increase in KM for MgATP and approximately 7-fold in KM for R-MVP.
Approximately 20000-fold decrease in Vmax for MgATP.
Approximately 3-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in KM for MgATP and no change in KM for R-MVP.
Approximately 3000-fold decrease in Vmax for MgATP and R-MVP. No change in KM for MgATP and approximately 3-fold increase in KM for R-MVP.
Approximately 4-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and R-MVP.
Approximately 500-fold decrease in Vmax for MgATP and R-MVP. Approximately 3-fold increase in KM for MgATP and R-MVP.
Approximately 65-fold decrease in Vmax for MgATP and R-MVP. Approximately 8-fold increase in KM for MgATP and 60-fold increase in KM for R-MVP.
Approximately 7-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in KM for MgATP and 5-fold increase in KM for R-MVP.
Approximately 8-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in KM for MgATP and R-MVP.
Approximately 85-fold decrease in Vmax for MgATP and R-MVP. Approximately 5-fold increase in KM for MgATP and R-MVP.
Approximately 9-fold decrease in Vmax for MgATP and R-MVP. Approximately 10-fold increase in KM for MgATP and R-MVP.
In POROK1; results in reduced expression and solubility; disturbs subcellular localization with punctate rather than diffuse cytoplasmic distribution.
In POROK1; unknown pathological significance.
Abolished androsterone glucuronosyltransferase activity; no change in hyodeoxycholic acid and tetrachlorocatechol glucuronosyltransferase activities.
Abolished androsterone glucuronosyltransferase activity; reduced hyodeoxycholic acid and tetrachlorocatechol glucuronosyltransferase activities.
Abolished androsterone, hyodeoxycholic acid and tetrachlorocatechol glucuronosyltransferase activities.
Reduced androsterone and tetrachlorocatechol glucuronosyltransferase activities; abolished hyodeoxycholic acid glucuronosyltransferase activity.
Reduced androsterone, hyodeoxycholic acid and tetrachlorocatechol glucuronosyltransferase activities.
Major facilitator superfamily (MFS) profile
Solute carrier family 2, facilitated glucose transporter member 11
Found in a patient with hidrotic ectodermal dysplasia, abortive features of oculodentodigital dysplasia and extensive hyperkeratosis of the skin; unknown pathological significance; the patient also carries GJB2 variant H-127.
In EKVP3; loss of localization to the plasma membrane, retention in the Golgi apparatus.
In HLHS1; unknown pathological significance; associated with Q-362; abolishes phosphorylation by PKA and PKC.
In HLHS1; unknown pathological significance; associated with Q-376; abolishes phosphorylation by PKA and PKC.
In HSS; overlapping features with oculodentodigital dysplasia.
In ODDD; atypical form of ODDD characterized by the predominance of the ocular involvement and by the absence of hand and/or foot syndactyly and absence of any neurologic signs.
In ODDD; de novo mutation found in a sporadic case.
In PPKCA1; can form functional gap junctions; results in enhanced hemichannel activity that causes increased cell death.
In heart malformations; shows abnormalities in the regulation of cell-cell communication as compared with cells expressing normal GJA1.
Phosphoserine; by PKC/PRKCG and PKC/PRKCD
In EPVB6D; decreased expression at the mRNA level; undetectable at the protein level in patient's fibroblasts.
Important loss of interaction with YAP1.
In SCRA; loss of interaction with YAP1 and also activation by YAP1.
26S proteasome non-ATPase regulatory subunit 3
Tigger transposable element-derived protein 3
Involved in the interaction with H3C15 and H3C1
Reduced interaction with H3C15 and H3C1.
Helical; Signal-anchor for type III membrane protein
Zinc finger and BTB domain-containing protein 42
In MC4DN5; unknown pathological significance.
Leucine-rich PPR motif-containing protein, mitochondrial
Pentacotripeptide-repeat region of PRORP
Significantly reduced half-life; when associated with S-60.
Significantly reduced half-life; when associated with S-62.
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.
Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport
Mediates proton transfer from the protein to the inner aqueous phase
Required for localization in the endoplasmic reticulum
Restores chloride translocation, but not proton transport; when associated with A-281.
Submaxillary gland androgen-regulated protein 3B
Reduces affinity for KLRF2 over 10'000-fold.
Impairs interaction with LMOD2 and TMOD1.
In CMH3; no change in homodimerization; decreased in hom odimer thermal stability; decreased in actin binding; increased calcium-dependent regulation of myosin binding to actin filaments; dominant effect in the homodimer.
In CMH3; no change in homodimerization; no change in homodimer thermal stability; decreased actin binding; recessive effect in the homodimer; increased calcium-dependent regulation of myosin binding to actin filaments; dominant effect in the homodimer.
In isoform 2, isoform 3, isoform 7, isoform 8 and isoform 9.
Increased formation of actin stress fibers.
Loss of phosphorylation and decreased formation of actin stress fibers.
In XLID19; kinase activity is decreased but not abolished.
In a gastric adenocarcinoma sample; somatic mutation.
In a glioblastoma multiforme sample; somatic mutation.
Phosphoserine; by autocatalysis and MAPKAPK2
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.
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.
No effect on ceramide hydrolase activity.
Required for correct folding and localization
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.
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 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.
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 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.
Involved in the recognition of the lipid substrate on the exoplasmic side
Involved in the release of the transported lipid into the cytosolic leaflet
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.
Loss of kinase activity and of ability to activate NEK11. Loss of phosphorylation of CCDC102B.
Required for microtubule binding and for localization to the centrosomes
RNA 3'-terminal phosphate cyclase insert
RNA 3'-terminal phosphate cyclase-like protein
N-linked (GlcNAc...) asparagine; partial
Natural cytotoxicity triggering receptor 1
Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein
0.1% enzymatic activity; no intramolecular processing.
Complete loss of enzymatic activity; no intramolecular processing.
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.
Abolishes binding to phosphorylated EGFR.
Abolishes interaction with and activation of GNAI3 and also abolishes recruitment of GNAI3 to EGFR. Reduced EGFR autophosphorylation and SH2 adapter recruitment, reduced localization of EGFR at the cell membrane following ligand stimulation with increased endosomal localization, reduced cell migration and increased cell proliferation. Abolishes enhancement of AKT signaling. Abolishes interaction with GNAS.
Abolishes phosphorylation and leads to reduced AKT phosphorylation, impaired formation of actin stress fibers and impaired cell migration abolishes interaction with PIK3R1 and activation of PI3K, reduces phosphorylation of Ser-1417 but does not affect interaction with or activation of GNAI3; when associated with F-1799.
Abolishes phosphorylation and leads to reduced AKT phosphorylation, impaired formation of actin stress fibers and impaired cell migration, abolishes interaction with PIK3R1 and activation of PI3K activity, reduces phosphorylation of Ser-1417 but does not affect interaction with or activation of GNAI3; when associated with F-1765.
Does not affect binding to phosphorylated EGFR.
Increases binding to phosphorylated EGFR.
No effect on guanine nucleotide exchange factor activity.
Phosphomimetic mutant which abolishes interaction with GNAI3, inhibits guanine nucleotide exchange factor activity, inhibits cell migration and triggers cell proliferation. Retains ability to bind to GNAS. Increased inhibition of GNAS; when associated with D-1675.
Phosphomimetic mutant which has no effect on tyrosine phosphorylation.
Phosphomimetic mutant which results in slight increase in binding to GNAI3 and GNAS. Increased inhibition of GNAS; when associated with D-1690.
Phosphorylation-deficient mutant which disrupts actin organization, cell migration and lamellipodia formation but has no effect on tyrosine phosphorylation.
Phosphorylation-deficient mutant which disrupts binding to GNAI3 and GNAS.
Phosphorylation-deficient mutant which retains the ability to bind GNAI3.
SH2-like; required for interaction with growth factor receptors
Acyl-coenzyme A synthetase ACSM4, mitochondrial
PC-esterase domain-containing protein 1B
Gypsy retrotransposon integrase-like protein 1
Necessary for interaction with RAB11A, subcellular location, homo- or heterooligomerization
Decreased interaction with free histones.
Sperm microtubule associated protein 2-like
1000-fold reduction in activity, inhibits equally PP1 and PP2A.
Protein phosphatase 1 regulatory subunit 1A
In CVID14; increased protein abundance in patient-derived B lymphocytes; impairs immature B cell differentiation.
Interferon regulatory factor 2-binding protein 2
Abolished interaction with SPG21 and induced T-cell activation.
Abrogates the interaction with MHCII and T cell activation.
Has no effect on the interaction with MHCII. Impairs recognition by OKT4 antibody.
Increases the affinity for MHCII; when associated with W-70; R-85 and R-88.
Increases the affinity for MHCII; when associated with Y-65; R-85 and R-88.
Increases the affinity for MHCII; when associated with Y-65; W-70 and R-85.
Increases the affinity for MHCII; when associated with Y-65; W-70 and R-88.
Loss of Nef-induced CD4 down-modulation.
Loss of homodimerization; when associated with A-445.
Loss of homodimerization; when associated with A-447.
In allele TGFBR1*6A; could be a tumor susceptibility allele.
Loss of phosphorylation on threonine residues. Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with A-187; A-189 and A-191.
Loss of phosphorylation. Loss of response to TGF-beta.
Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-189.
Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-187 and A-191.
Loss of threonine phosphorylation, reduced phosphorylation on serine residues and loss of response to TGF-beta; when associated with 185-VV-186; A-189 and A-191.
Reduced phosphorylation. Reduced response to TGF-beta.
receptor protein serine/threonine kinase
Abolishes DNA-binding to the CDK1 promoter; when associated with Y-525.
Abolishes DNA-binding to the CDK1 promoter; when associated with Y-527.
Critical for interaction with target DNA
29kDa cytosolic podoplanin intracellular domain
Does not affect localization at cell surface protrusions. Does not induce reorganization of the actin cytoskeleton. Increases cell migration collectively. Does not significant change RHOA activation. No effect on interaction with CD44. Impairs interaction with the EZR and MSN. Impairs epithelial to mesenchymal transition. Does not change localization at invadopodium. Fails to assemble into rings. Fails invadopodia-mediated ECM degradation.
Eliminates induction of platelet aggregation.
Highly decreases interaction with the EZR and MSN. Induces an intermediate phenotype between epithelial and mesenchymal. Does not affect localization at cell surface protrusions. Induces reorganization of the actin cytoskeleton oncomitantly with the induced morphological changes. Increases cell migration individually. Increases invasiveness. Enhances RHOA activity. Colocalizes at cell-surface protrusions with RHOA and RAC1.
Impairs interaction with the EZR and MSN. Impairs epithelial to mesenchymal transition. Does not affect localization at cell surface protrusions. Does not induce reorganization of the actin cytoskeleton. Increases cell migration collectively.
Prevents self-assembly and association to lipid rafts. Reduces the recruitment to invadopodium. Disrupts assembly into adhesion rings. Fails invadopodia-mediated ECM degradation.
Requires for dimerization and lipid rafts association
Requires for interaction with MSN and EZR
In CHNG6, decreases transcriptional activity, decreases T3 binding) (Ref.25.
In CHNG6, reduces T3 binding, impairs thyroid hormone-dependent transcriptional activation, no effect on DNA-binding) (Ref.24.
In CHNG6; atypical phenotype; weak reduction in transcriptional activation.
In CHNG6; no effect on T3 binding; no effect on thyroid hormone-dependent transcriptional activation.
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.
Tetratricopeptide repeat protein 19, mitochondrial
Cilia- and flagella-associated protein 107
STE20-related kinase adapter protein beta
In THC4; increases the pro-apoptotic function by triggering caspase activation more efficiently than wild-type; does not affect the redox function.
Inhibits interaction with BLNK. Inhibits activation of several downstream signaling pathways.
Inhibits interaction with CSK. Stimulates activation of several downstream signaling pathways.
Proline-rich region necessary for constitutive interaction with LYN
SLP adapter and CSK-interacting membrane protein
Receptor-binding cancer antigen expressed on SiSo cells
Mediates endoplasmic reticulum retention
Results in loss of ER retention signal and relocalization at the Golgi apparatus.
Interferes with dimerization and reduces activity by 94%.
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.
Zinc finger SWIM domain-containing protein 6
Diacylglycerol O-acyltransferase 2-like protein 6
Necessary and sufficient to promote mitochondrial fission
Does not affect phosphorylation by PLK1.
Strongly impairs phosphorylation by PLK1.
Found in a patient with spastic paraplegia; unknown pathological significance.
In ILLD; may act as a disease modifier aggravating the phenotype; found in patients that carried additional mutations C-344 and/or L-567; when assayed in yeast, does not exhibit any phenotype; when assayed in yeast in association with L-567, increases L-567-induced growth retardation and reduction in methionine incorporation.
In ILLD; when assayed in yeast, induces a slight growth retardation and reduction in methionine incorporation; may interfere with efficient substrate binding.
In ILLD; when assayed in yeast, reduces methionine incorporation; when assayed in yeast in association with T-393, induces growth retardation and strong reduction in methionine incorporation; may interfere with efficient substrate binding.
In TTD9; unknown pathological significance; homozygous patient cells show decreased methionyl-tRNA aminoacylation; decreased protein abundance in homozygous patient cells.
In a breast pleomorphic lobular carcinoma sample; somatic mutation.
Mitogen-activated protein kinase kinase kinase 19
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.
Required for association with the NAA10-NAA15 complex
In ARVD8; unknown pathological significance.
In a case of recessive arrhythmogenic right ventricular cardiomyopathy with skin abnormalities and woolly hair.
Cyclic AMP-dependent transcription factor ATF-2
Essential for its histone acetyltransferase activity
Impairs phosphorylation by PLK3. Weak histone acetyltransferase activity.
Phosphoserine; by PKC/PRKCA and PKC/PRKCB
Phosphothreonine; by MAPK1, MAPK3, MAPK11, MAPK12, MAPK14 and PLK3
Reduced phosphorylation and repression of c-Jun-mediated activation of transcription.
Weak histone acetyltransferase activity.
FERM, ARHGEF and pleckstrin domain-containing protein 1
Zinc finger CCCH domain-containing protein 4
Associated with resistance to anticancer indisulam.
Associated with resistance to anticancer indisulam; abolished degradation by the DCX(DCAF15) complex in presence of indisulam.
Associated with resistance to anticancer indisulam; decreased interaction with the DCX(DCAF15) complex in presence of indisulam; abolished degradation by the DCX(DCAF15) complex in presence of indisulam.
Zinc finger Ran-binding domain-containing protein 2
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
Loss of polyubiquitination of PCNA. Impairs interaction with SHPRH.
In COXPD49; patient cells have reduced MIEF2 protein levels and show elongated mitochondria and increased mitochondrial fusion events.
Unable to associate with DNM1L into filaments forming the tubular structures that wrap around the scission site.
Beta/gamma crystallin domain-containing protein 1
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
Abolished homodimerization and disulfide bond formation.
CCA tRNA nucleotidyltransferase 1, mitochondrial
Decreased CCA tRNA nucleotidyltransferase activity; abolished homodimerization and disulfide bond formation.
In SIFD; decreased CCA tRNA nucleotidyltransferase activity; abolished homodimerization and disulfide bond formation.
In SIFD; loss of CCA tRNA nucleotidyltransferase activity.
In SIFD; loss of CCA tRNA nucleotidyltransferase activity; decreased stability.
In SIFD; reduced CCA tRNA nucleotidyltransferasevactivity; decreased stability.
In SIFD; unknown pathological significance.
May assist in discriminating ATP from CTP
Essential for determining substrate specificity
Increased triglyceride hydrolase and reduced phospholipase activity.
Loss of triglyceride hydrolase and phospholipase activity.
In POF16; unknown pathological significance; affects nuclear localization; the mutant exhibits a punctate localization in the nucleus.
No effect on phosphorylation, no effect on subcellular location.
No effect on phosphorylation. Abolishes phosphorylation and induces nuclear restriction; when associated with A-541.
Reduces phosphorylation and induces partial relocation into the cytoplasm.
Strongly reduces phosphorylation and induces partial relocation into the cytoplasm.
Strongly reduces phosphorylation. Abolishes phosphorylation and induces nuclear restriction; when associated with A-537.
Necessary for tight junction and adherens junction localization; Requires for interaction with PARD3
Inhibits weakly translational repression activity. Inhibits interaction with CCND1 and cell cycle arrest.
Required and sufficient for interaction with KDM1A
Loss of binding to (PtdIns(3)P) and (PtdIns(3,4)P2).
No effect on binding to 'Lys-48'- or 'Lys-63'-tetraubiquitin chains.
Strongly decreased binding to 'Lys-48' or 'Lys-63'-tetraubiquitin chains.
Ubiquitin carboxyl-terminal hydrolase MINDY-2
Found in a family with autosomal dominant macular dystrophy; unknown pathological significance.
Found in autosomal dominant macular dystrophy; unknown pathological significance; affects guanylate cyclase regulator activity resulting in a constitutively active form at physiologic calcium concentrations; no change of affinity for calcium ions; increased affinity for magnesium ions.
In COD3; constitutive activation of GUCY2D.
In COD3; exhibits an about 18-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal.
In COD3; exhibits an about 28-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal.
In COD3; exhibits an about 6-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal.
In COD3; results in impaired guanylate cyclase regulator activity leading to increased GUCY2D activity.
In COD3; results in impaired guanylate cyclase regulator activity; at high calcium ion concentrations the mutant protein stimulates GUCY2D activity while the wild-type inhibits it.
In COD3; results in impaired guanylate cyclase regulator activity; at low calcium concentrations the mutant protein stimulates GUCY2D less efficiently than the wild-type but it remains active at high calcium concentrations causing persistent GUCY2D stimulation.
In COD3; some subjects may present a moderately severe cone-rod dystrophy; unknown pathological significance; causes a decrease in the number of bound calcium ions from 3 to 2, without changing the activity profile.
In COD3; unknown pathological significance.
In CORD14; affects guanylate cyclase regulator activity resulting in constitutive activation of GUCY2D at physiologic calcium concentrations; 10-fold lower affinity for calcium ions.
In CORD14; affects guanylate cyclase regulator activity resulting in constitutive activation of GUCY2D at physiologic calcium concentrations; altered tertiary structure; no change of affinity for calcium ions; increased affinity for magnesium ions.
In CORD14; results in impaired guanylate cyclase regulator activity; at low calcium concentrations the mutant protein stimulates GUCY2D as the wild-type while at high calcium concentrations it does not fully inhibit GUCY2D; decreased affinity for calcium ions.
In CORD14; results in impaired guanylate cyclase regulator activity; interferes with GCAP1 calcium-dependent transition from activator to inhibitor of GUCY2D; the mutant protein remains active at high calcium concentrations causing persistent GUCY2D stimulation.
In a patient with an atypical form of retinitis pigmentosa; unknown pathological significance.
In HH19; rare variant associated with susceptibility to disease; the patient carries a second mutation in the HH-associated gene FGFR1.
In HH19; rare variant associated with susceptibility to disease; the patient carries a second variant in the HH-associated gene SPRY4.
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.
In isoform 2, isoform 3, isoform 4 and isoform 6.
Facilitates phospholipid membrane insertion
In CMD1W; significantly alters metavinculin-mediated cross-linking of actin filaments.
Phosphotyrosine; by SRC-type Tyr-kinases
8 X 7 AA tandem repeats of [PT]-[AT]-A-[ENT]-[PT]-[PTS]-[AG]
Interaction with phosphoserine on interacting protein
Protein N-terminal asparagine amidohydrolase
Does not significantly alter affinity for PIP2, but mutant channels do not open despite binding PIP2.
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 localization to the lysosome membrane and promotes relocalization to the plasma membrane; when associated with 14-A-A-15.
Abolished localization to the lysosome membrane and promotes relocalization to the plasma membrane; when associated with 318-A-A-319. Does not affect interaction with TASL.
Abolished transmembrane transporter activity. Abolished interaction with TASL.
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.
In HAE7; unknown pathological significance.
In AN1 and ocular anterior segment anomalies; loss of DNA binding ability.
In AN1; mild; shows 50% lower DNA-binding and transactivation ability than the wild-type protein.
In AN1; shows almost no binding efficiency; transcriptional activation ability is about 50% lower than that of the wild-type protein.
In AN1; shows almost no binding efficiency; transcriptional activation ability is about 80% of that of the wild-type protein.
In AN1; shows only one-quarter to one-third the binding ability of the normal wild-type protein; exhibits normal transactivation.
In AN1; the mutant homeodomain binds DNA as well as the wild-type homeodomain; the mutant does not modify the DNA-binding properties of the paired domain; the steady-state levels of the full-length mutant protein are higher than those of the wild-type one; a responsive promoter is activated to a higher extent by the mutant protein than by the wild-type protein; the presence of the mutation reduces sensitivity to trypsin digestion.
In ASGD5; also found in patients with congenital cataract and foveal hypoplasia.
In BONH; significant impairment of ability to activate transcription.
In COAD and COLON; significant impairment of transcriptional activation ability.
In FVH1; unknown pathological significance.
In a family with nystagmus associated with a variant form of aniridia.
In foveal hypoplasia; associated with presenile cataract syndrome.
In morning glory disk anomaly; significant impairment of transcriptional activation ability.
Required for suppression of NFATC1-mediated transcription
Shows about two-fold higher binding efficiency than the normal wild-type protein; transcriptional activation ability is about 89% of that of the wild-type protein.
N-acetylthreonine; in Ubiquitin-conjugating enzyme E2 G1, N-terminally processed
Ubiquitin-conjugating enzyme E2 G1, N-terminally processed
Complete loss of phosphorylation by PRKD1.
N-terminal EF-hand calcium-binding protein 3
U6 snRNA-associated Sm-like protein LSm5
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.
Anaphase-promoting complex subunit 4-like WD40
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.
Interaction with U4 snRNA and with the 7-methylguanosine cap of RNA molecules
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 exonuclease activity; when associated with A-114 and A-116.
Abolishes exonuclease activity; when associated with A-114 and A-258.
Abolishes exonuclease activity; when associated with A-116 and A-258.
Decreased protein stability and catalytic activity; when associated with S-119 or T-119.
Loss of catalytic activity. Cannot prevent cell detachment after depletion of the endogenous protein.
Loss of catalytic activity. Decreased protein stability and catalytic activity; when associated with A-72.
Loss of glycosylation site. Abolishes secretion. No effect on catalytic activity.
No effect. Reduces activity by 70%; when associated with S-512.
Reduces activity by 40%. Reduces activity by 70%; when associated with S-509.
Abolishes binding to the telomeric double-stranded 5'-TTAGGG-3' repeat.
Loss of catalytic activity. Loss of ATP binding.
Protein adenylyltransferase SelO, mitochondrial
Slightly enhances redox complex formation.
In a breast infiltrating ductal carcinoma sample; somatic mutation.
In an ovarian mucinous carcinoma sample; somatic mutation.
Lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase
Found in families with neurodegeneration with brain iron accumulation; uncertain pathological significance.
In NBIA4 and SPG43; impairs subcellular localization to the endoplasmic reticulum or mitochondrion.
In NBIA4; impairs subcellular localization to the endoplasmic reticulum or mitochondrion.
In NBIA4; no effect on its subcellular localization; no cytosolic redistribution seen in response to oxidative stress.
In NBIA4; predominantly cytosolic distribution with a localization also seen in the mitochondrial matrix; no cytosolic redistribution seen in response to oxidative stress; patient fibroblasts accumulate high levels of mitochondrial calcium and are more prone to oxidative stress-induced apoptosis.
In NBIA4; unknown pathological significance.
FRAS1-related extracellular matrix protein 3
V-type proton ATPase 16 kDa proteolipid subunit c
Does not inhibit cell membrane localization. Inhibits interaction with CA2 and bicarbonate transport.
Does not inhibit interaction with CA2. Does not inhibit interaction with CA2 and bicarbonate transport in PMA-induced cells.
Does not inhibit interaction with CA2. Inhibits interaction with CA2 and bicarbonate transport in PMA-induced cells.
Reduced chloride oxalate exchanger activity.
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1
Echinoderm microtubule-associated protein-like 5
Histone-arginine methyltransferase CARM1
Loss of FBXO9-mediated ubiquitination and subsequent proteasomal degradation.
Loss of protein methyltransferase activity without affecting ability to regulate replication fork progression.
In BSVD3; loss of galactosyltransferase activity.
Loss of galactosyltransferase activity; when associated with A-166.
Loss of galactosyltransferase activity; when associated with A-168.
Loss of galactosyltransferase activity; when associated with A-461.
Loss of galactosyltransferase activity; when associated with A-463.
No effect on galactosyltransferase activity; when associated with A-585.
No effect on galactosyltransferase activity; when associated with A-587.
Small decrease of galactosyltransferase activity.
Abolishes self-association, protein aggregation and cell death.
Interferon regulatory factor 2-binding protein 1
In MC4DN2 and MYP6; reduced cytochrome c oxidase subunit II synthesis and reduced ability to regulate cellular copper homeostasis.
In MC4DN2; renders the protein unstable.
In MYP6; remains stable in mitochondria; reduces the level of the protein copurifying with COA6 by 80%.
In MYP6; unknown pathological significance.
Loss of interferon-gamma induced phosphorylation.
In HLCS deficiency; 14% of activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form.
In HLCS deficiency; 22% activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form.
In HLCS deficiency; <10% activity; has normal or low KM values for biotin (non-KM mutant).
In HLCS deficiency; benign variant; conserves enzymatic wild-type activity.
In HLCS deficiency; has normal or low KM values for biotin (non-KM mutant).
In HLCS deficiency; has normal or low KM values for biotin (non-KM mutant); growth of patients' fibroblasts is compromised compared with normal fibroblasts; patients cells are not sensitive to biotin-depletion from the media; growth rates cannot be restored by re-administration of biotin; enzyme activity is severely compromised and cannot be increased by additional biotin; turn-over rate for the mutant protein is double that of wild-type enzyme.
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..
Tumor suppressor candidate gene 1 protein
Abolished interaction with OXSR1/OSR1 and STK39/SPAK, preventing phosphorylation and activation.
Abolished sodium and chloride ion cotransporter activity.
Decreased phosphorylation by OXSR1/OSR1 and STK39/SPAK.
In GTLMNS; 27% residual Na(+) uptake activity; increased MAPK1/3 (ERK1/2) phosphorylation in response to IL18; no effect on localization at the plasma membrane.
In GTLMNS; 40% residual Na(+) uptake activity; increased MAPK1/3 (ERK1/2) phosphorylation in response to IL18; no effect on localization at the plasma membrane.
In GTLMNS; 48% residual Na(+) uptake activity; no effect on localization at the plasma membrane.
In GTLMNS; 54% residual Na(+) uptake activity; no effect on localization at the plasma membrane.
In GTLMNS; 58% residual Na(+) uptake activity; decreased MAPK1/3 (ERK1/2) phosphorylation in response to IL18; partial loss of localization at the plasma membrane.
In GTLMNS; 68% residual Na(+) uptake activity; partial loss of localization at the plasma membrane.
In GTLMNS; associated with deletion of N-566.
In GTLMNS; complete loss Na(+) uptake activity; partial loss of localization at the plasma membrane.
In GTLMNS; does not affect MAPK1/3 (ERK1/2) phosphorylation in response to IL18.
In GTLMNS; unknown pathological significance.
Reduced sensitivity to thiazide diuretics.
Reduced sensitivity to thiazide diuretics. Reduced sodium and chloride ion cotransporter activity.
Reduced sodium and chloride ion cotransporter activity.
Strongly reduced sodium and chloride ion cotransporter 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
Short-chain dehydrogenase/reductase family 42E member 1
Abolishes generation of the 104 kDa chain.
Decreased proteolytic processing; when associated with 116-A--A-119.
Decreased proteolytic processing; when associated with 66-A--A-69.
Strongly increases generation of the 104 kDa chain.
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
Leucine-rich repeat and fibronectin type-III domain-containing protein 5
FLYWCH-type zinc finger-containing protein 1
Abolishes interaction with CBX5; when associated with E-240.
Abolishes interaction with CBX5; when associated with E-242.
Necessary for homodimerization and competence for chromatin assembly
Immunoglobulin-like and fibronectin type III domain-containing protein 1
In CMH29; loss-of-function variant unable to rescue heart defects and cardiac failure in zebrafish morphants.
Weak interaction with CUL3. Weak autoubiquitination.
Mas-related G-protein coupled receptor member E
Fails to undergo proteolytic cleavage and is unable to activate ENaC.
In DFNB8; fails to undergo proteolytic cleavage and is unable to activate ENaC.
Disintegrin and metalloproteinase domain-containing protein 20
Inactive Rho GTPase-activating protein 11B
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.
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.
Phosphatidylinositol 4,5-bisphosphate (PIP2) binding
Ubiquitin carboxyl-terminal hydrolase 17-like protein 17
Transcription factor CBF/NF-Y/archaeal histone
Basic leucine zipper transcriptional factor ATF-like 3
Janus kinase and microtubule-interacting protein 2
Found in a patient with atrial septal defects; unknown pathological significance.
Protein tyrosine phosphatase receptor type C-associated protein
WAP four-disulfide core domain protein 13
Abolishes interaction with NCOA1, NCOA2 and NCOA3.
Decreases phosphorylation and transactivation activity. Abolishes AF-1 transactivation. Insensitive to PPP5C inhibition of transactivation activity.
Destabilizes the receptor and decreases its affinity for estradiol at 25 degrees Celsius, but not at 4 degrees Celsius.
Enhances transactivation activity. Insensitive to PPP5C inhibition of transactivation activity.
Has higher transcriptional activity in the absence of wild type ER. Inhibits transcriptional activity when coexpressed with the wild type receptor.
In ESTRR; highly decreased estrogen receptor activity.
In ESTRR; results in highly reduced activity.
In a 80 kDa form found in a breast cancer line; contains an in-frame duplication of exons 6 and 7.
Loss of cyclin A-dependent induction of transcriptional activation.
Loss of hormone binding capacity and temperature-sensitive loss in DNA-binding.
Loss of transmembrane localization, no effect on peripheral membrane localization. Impairs activation of estrogen-induced activation of NOS3 and production of nitric oxide. No effect on binding to ERES.
Modulating (transactivation AF-1); mediates interaction with MACROD1
Reduces PELP1-mediated activation of transcriptional activity.
Coiled-coil domain-containing protein 68
Sodium- and chloride-dependent glycine transporter 1
Calcium and integrin-binding family member 2
Found in a family with deafness; unknown pathological significance; the patient also carries a likely disease-causing mutation in PDZD7.
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.
Dual specificity mitogen-activated protein kinase kinase 5
ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited form
Does not affect glycosylation by C.rodentium protein NleB.
Drastic reduction of the extent and significant prolongation of the lag phase of free radical-induced aggregation.
Glyceraldehyde 3-phosphate dehydrogenase NAD(P) binding
Glyceraldehyde-3-phosphate dehydrogenase
Increased free radical-induced aggregation.
Increased resistance to free radical-induced aggregation.
Inhibits S-nitrosylation of Cys-247; when associated with M-245.
Inhibits S-nitrosylation of Cys-247; when associated with M-250.
Markedly reduced glycolytic activity; when associated with S-152 and S-156. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247.
Markedly reduced glycolytic activity; when associated with S-152 and S-247. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247.
Markedly reduced glycolytic activity; when associated with S-156 and S-247. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247. Abolished interaction with TRAF2 and TRAF3.
No effect on free radical-induced aggregation.
S-nitrosocysteine; in reversibly inhibited form
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial
AFG2-interacting ribosome maturation factor
Abolishes phosphorylation by CK2 kinase; when associated with A-104 and A-134.
Abolishes phosphorylation by CK2 kinase; when associated with A-104 and A-182.
Abolishes phosphorylation by CK2 kinase; when associated with A-134 and A-182.
Does not affect FBXL15-mediated ubiquitination.
NEDD4-like E3 ubiquitin-protein ligase WWP2
Loss of interaction with TESK1, however no effect on interaction with ILK; when associated with D-4.
Loss of interaction with TESK1, however no effect on interaction with ILK; when associated with D-8.
Required for interaction with TESK1 and ILK
In DIH4; decreased retinoic acid biosynthetic process.
In DIH4; unknown pathological significance.
IQ motif and SEC7 domain-containing protein 2
In XLID1; decreased guanine nucleotide exchange factor activity.
Impairs the expression of KLRD1-KLRC2 on the cell surface.
Increases the affinity for HLA-E to a value similar to that observed for HLA-E-KLRD1-KLRC1 complex.
NKG2-C type II integral membrane protein
Sodium/potassium-transporting ATPase subunit beta-3
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
Coiled-coil domain-containing protein 85B
Loss of interaction with TCF7L2 and loss of suppression of CTNNB1 activity. Loss of cell growth inhibition.
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 TPDS1; significantly increased risk for renal cell carcinoma.
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
In NPHS5; unknown pathological significance.
In PIERS and NPHS5; with mild ocular abnormalities.
In PIERS and NPHS5; with mild ocular abnormalities; associated with F-1393.
In PIERS and NPHS5; with mild ocular abnormalities; associated with K-1380.
In RHABDO1; associated with disease susceptibility.
In RHABDO1; associated with disease susceptibility; greatly reduced protein levels detected by Wester blot in skeletal muscle from a homozygous patient.
Reduced binding to phosphatidylinositol 3,4-bisphosphate.
Reduced binding to phosphatidylinositol 4,5-bisphosphate.
Mitogen-activated protein kinase kinase kinase 3
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
Decreases HIV-1 binding/entry in cells as well as virus replication.
C4-type zinc-finger of DNA polymerase delta
DNA-directed DNA polymerase family B exonuclease
DNA-directed DNA polymerase family B multifunctional
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.
Golgin subfamily A member 6-like protein 6
In MKS14; unknown pathological significance.
Thioredoxin domain-containing protein 15
Does not interact with DR1 and drastically affects transcriptional repression; when associated with E-330.
Does not interact with DR1 and drastically affects transcriptional repression; when associated with E-332.
Interacts with DR1 and partially affects transcriptional repression; when associated with E-330.
Interacts with DR1 and partially affects transcriptional repression; when associated with E-332.
Necessary for transcriptional repression and sufficient for interaction with DR1
Nuclear factor interleukin-3-regulated protein
In CSS7; abolishes interaction with acetylated histone H3; strongly decreased interaction with methylated histone H3.
In CSS7; abolishes interaction with acetylated or methylated histone H3.
Strongly decreased interaction with histones H3 and H4 and loss of function; when associated with A-275 and A-300.
Strongly decreased interaction with histones H3 and H4 and loss of function; when associated with A-275 and A-346.
Strongly decreased interaction with histones H3 and H4 and loss of function; when associated with A-300 and A-346.
Important for superfibronectin formation
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.
Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-?)
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.
V region (type III connecting segment, IIICS)
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.
V-set and transmembrane domain-containing protein 1
CCR4-NOT transcription complex subunit 8
Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated with A-40.
Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated with A-42.
V-set and immunoglobulin domain-containing protein 1
Abolishes interaction with GABARAP and MAP1LC3C.
Decreased interaction with GABARAP, no effect on interaction with MAP1LC3B; when associated with A-3343 and A-3344.
Decreased interaction with GABARAP, no effect on interaction with MAP1LC3B; when associated with A-3343 and A-3351.
Decreased interaction with GABARAP, no effect on interaction with MAP1LC3B; when associated with A-3344 and A-3351.
Decreases interaction with GABARAP and MAP1LC3C.
In MCPH18; increased cellular DVL3 protein levels as compared to the wild-type protein and loss of attenuation of Wnt signaling; when expressed in Drosophila, causes brain anomalies.
Sufficient for localization to p62 bodies/ALIS
WD repeat and FYVE domain-containing protein 3
Origin recognition complex subunit 4 C-terminal
In an ovarian mucinous carcinoma; somatic mutation.
Reduces phosphorylation upon DNA damage; when associated with A-406.
Reduces phosphorylation upon DNA damage; when associated with A-408.
Thyroid hormone receptor-associated protein 3
DNA-directed RNA polymerases I, II, and III subunit RPABC5
Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-817; A-820 and A-833.
Abolishes interaction with CBX1, CBX3 and CBX5; when associated with A-817; A-820 and A-840.
Abolishes interaction with CBX1, CBX3 and CBX5; when associated with when associated with A-817; A-833 and A-840.
Diminishes interaction with CBX5 and abolishes interaction with CBX1 and CBX5; when associated with A-820; A-833 and A-840.
Loss of phosphorylation. Loss of interaction with PSIP1; when associated with A-1392.
Loss of phosphorylation. Loss of interaction with PSIP1; when associated with A-1396.
Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-1392.
Phosphomimetic mutant. Significant increase in interaction with PSIP1; when associated with D-1396.
Pogo transposable element with ZNF domain
Probable disease-associated variant found in patients with ASD.
Putative ATP-dependent RNA helicase TDRD12
Leucine zipper putative tumor suppressor 3
CCR4-NOT transcription complex subunit 9
Type I cytokine receptor cytokine-binding
Zinc finger and BTB domain-containing protein 49
In CILD3; disease phenotype consistent with Kartagener syndrome.
Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-350 and R-381. Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-381.
Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-350 and R-383. Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-383.
Abolishes FBXL15-mediated ubiquitination and degradation; when associated with R-381 and R-381.
Fails to ubiquitinate RHOA; when associated with A-28.
Fails to ubiquitinate RHOA; when associated with A-85.
Loss of enzyme activity, without abolishing FBXL15-mediated ubiquitination.
In SCN5; patient fibroblasts are characterized by impaired motility and increased apoptosis.
Vacuolar protein sorting-associated protein 45
GATA zinc finger domain-containing protein 1
In DEE80; decreased protein levels; decreased cell surface presence of GPI-anchored proteins.
In DEE80; decreased protein levels; slightly decreased cell surface presence of GPI-anchored proteins.
In DEE80; no effect on protein levels; decreased cell surface presence of GPI-anchored proteins.
In DEE80; strongly decreased protein levels; decreased cell surface presence of GPI-anchored proteins.
In DEE80; strongly decreased protein levels; slightly decreased cell surface presence of GPI-anchored proteins.
In DEE80; unknown pathological significance.
Insulin-like growth factor-binding protein 7
Interaction with PYHIN1 and necessary for interaction with RFFL and RNF34
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.
Sufficient to promote the mitochondrial pathway of apoptosis
G-protein coupled receptor-associated sorting protein 1
Abolished E3 ubiquitin-protein ligase activity in threonine discharge assay, associated with enhanced thiol-sensitive ubiquitin adduct formation.
Abolished E3 ubiquitin-protein ligase activity.
Does not affect E3 ubiquitin-protein ligase activity.
Increased thiol-sensitive adduct formation.
Reduced E3 ubiquitin-protein ligase activity in threonine discharge assay.
Retains activity while also forming a discrete monoubiquitin adduct that is resistant to thiolysis but is reversible after base treatment.
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.
Interaction with the C-terminus of CDCA1 and the SPBC24-SPBC25 subcomplex
Interaction with the N-terminus of CDCA1
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.
Required for reduction of TSC22D1 protein stability
Translationally-controlled tumor protein
In SPGF21; no effect on protein expression; unknown pathological significance.
Actin, aortic smooth muscle, intermediate form
In MYMY5 and MSMDS; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract.
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
N-acetylglutamate; in Actin, aortic smooth muscle
In XLID41; causes reduced binding and recycling of RAB3A.
Endogenous Bornavirus-like nucleoprotein 1
50% reduction in 3'-to-5'exoribonuclease activity.
Disruption of homodimerization and loss of 3'-to-5'exoribonuclease activity; when associated with A-178 or A-215.
Disruption of homodimerization and loss of 3'-to-5'exoribonuclease activity; when associated with A-178.
Disruption of homodimerization and loss of 3'-to-5'exoribonuclease activity; when associated with A-179.
Disruption of homodimerization and loss of 3'-to-5'exoribonuclease activity; when associated with R-179 or A-179.
Loss of 3'-to-5'exoribonuclease activity.
No effect on 3'-to-5'exoribonuclease activity.
DNA-directed DNA polymerase family A palm
In PEOA1 and MTDPS4A; unknown pathological significance.
In PEOA1; can underlie parkinsonism; 45-fold decrease in apparent binding affinity for the incoming nucleoside triphosphate; 2-fold less accurate for basepair substitutions than wild-type.
In PEOB1, SANDO, SCAE and MTDPS4A; results in clearly decreased activity, DNA binding and processivity of the polymerase.
In PEOB1; unknown pathological significance.
In PEOB1; with absence of progressive external ophthalmoplegia.
In SANDO, SCAE and MTDPS4A; unknown pathological significance.
In SANDO; shows DNA binding affinity and processivities similar to the controls.
Important for selectivity toward medium-length fatty acids
Moderately reduced catalytic activity. Enhances activity with acyl-CoA with C18 and C20 fatty acid chains.
Strongly reduced catalytic activity. Enhances activity with acyl-CoA with C12 and C14 fatty acid chains.
In isoform 2, isoform 3, isoform 4 and isoform 5.
Predominantly cytoplasmic rather than nuclear localization.
Can be associated with insulin resistance.
Protein phosphatase 1 regulatory subunit 3A
Mas-related G-protein coupled receptor member X4
Abolishes interaction with RAD1; when associated with D-646.
Abolishes interaction with RAD1; when associated with D-656.
Impairs phosphorylation on S-656. Abolishes interaction with the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3.
Impairs phosphorylation. Impairs interaction with DNA and the RAD1-RAD9-HUS1 complex; does not affect interaction with RFC3.
Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RFC3, RFC4, ATM or ATR; when associated with A-646.
Reduces by 50% phosphorylation by ATR, and abolishes interaction with RAD1. Abolishes phosphorylation by ATR and checkpoint activation without affecting interaction with RFC3, RFC4, ATM or ATR; when associated with A-656.
Does not affect neither UBA5-binding nor thioester formation with UFM1.
Impairs binding to UBA5 and thioester formation with UFM1.
In NEDSG; decreased ability to form thioester bond with UFM1; decreased protein ufmylation.
Instead of the formation of an intermediate complex with a thiol ester bond between UFC1 (E2-like enzyme) and UFM1 (substrate), a stable complex with an O-ester bond is formed.
Ubiquitin-fold modifier-conjugating enzyme 1
In HTX5; decrease in signal transduction.
In HTX5; likely benign variant; decrease in signal transduction.
Almost complete loss of function. Lysis.
Loss of glycation mediated inactivation.
In ARCI1; skin phenotype consistent with lamellar ichthyosis.
In ARCI1; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma.
Protein-glutamine gamma-glutamyltransferase K
Neuronal PAS domain-containing protein 1
Fails to localize at the centromere during interphase.
Loss of kinase activity, autophosphorylation and tumor suppressor activity.
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.
tRNA N(3)-methylcytidine methyltransferase METTL2B
Decreased kinase activity without affecting much autophosphorylation status.
Does not autophosphorylation and kinase activity.
Impaired autophosphorylation and kinase activity.
In DEE30; no change in subcellular location.
Loss of interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-473.
Prevents phosphorylation and activation by STK11/LKB1 complex. Reduced inhibition of CRTC3-mediated transcriptional activity.
Putative serine/threonine-protein kinase SIK1B
RK-rich region; required for cAMP responsiveness and nuclear localization
Reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity.
Reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-575.
Strongly reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity.
Abolishes Ras activity increase and ERK1/2 phosphorylation.
Abolishes dimerization. Abolishes activation of HRAS.
Global loss of tyrosine phosphorylation. Abolishes interaction with FHL2 and HAX1.
Impairs phosphotyrosine binding by SH2 domain.
Important for dimerization and for HRAS activation
Important for lipid binding and for stimulation of cell migration
Abolishes nuclear export; when associated with A-349.
Abolishes nuclear export; when associated with A-353.
Cytoplasmic polyadenylation element-binding protein 3
Cilia- and flagella-associated protein 221
Adenine nucleotide translocase lysine N-methyltransferase
Does not affect mitochondrial localization.
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.
Transcription activation and HCFC1 interaction
In CMYP8; unknown pathological significance.
In MPD6; unknown pathological significance.
50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 213-E-L-214 and 294-E-L-295.
50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 213-E-L-214 and 423-E-L-424.
50-fold decrease in RNA-binding affinity, decreased location in cytoplasmic RNP, increased nuclear location; when associated with 294-E-L-295 and 423-E-L-424.
Insulin-like growth factor 2 mRNA-binding protein 1
Loss of binding to RBPR and loss of interaction with m6A-modified mRNA; when associated with 423-E-E-424.
Loss of binding to RBPR and loss of interaction with m6A-modified mRNA; when associated with 505-E-E-506.
Necessary for interaction with ELAVL4 and binding to TAU mRNA
Partial reduction in interaction with m6A-modified mRNA; when associated with E-213.
Partial reduction in interaction with m6A-modified mRNA; when associated with E-294.
Abolishes autoacetylation, represses transcription activity, does not inhibit its association with chromatin to promoter-specific regions and decreases the association of GTF2F1 with chromatin to promoter-specific regions.
Decreases BREd-dependent pre-initiation complex formation.
Defects in transcription start site selection. Supports a level of transcription equivalent to wild-type.
Does not inhibit interaction with TBP. Inhibits the recruitment of RNA polymerase II into the initiation complex.
Does not inhibit the formation of the TATA box-bound TBP ternary complex.
Inhibits interaction with RNA polymerase II; when associated with E-286 and E-290.
Inhibits interaction with RNA polymerase II; when associated with E-286 and E-295.
Inhibits interaction with RNA polymerase II; when associated with E-290 and E-295.
Inhibits interaction with SSU72; when associated with E-185 or E-189. Inhibits interaction with VP16; when associated with E-185. Inhibits RNA pol II transcription activation induced by VP16 but does not affect basal transcription; when associated with E-185.
Inhibits interaction with SSU72; when associated with E-193. Reduces interaction with SSU72; when associated with E-200. Inhibits interaction with VP16; when associated with E-200. Inhibits RNA pol II transcription activation induced by VP16 but does not affect basal transcription; when associated with E-200.
Necessary for TATA box-bound TBP complex formation
Reduces interaction with SSU72; when associated with E-185 or E-189. Inhibits interaction with VP16; when associated with E-189. Inhibits RNA pol II transcription activation induced by VP16 but does not affect basal transcription; when associated with E-189.
Reduces interaction with SSU72; when associated with E-193 or E-200. Inhibits interaction with VP16; when associated with E-193. Inhibits RNA pol II transcription activation induced by VP16 but does not affect basal transcription; when associated with E-193.
Reduces interaction with VP16; when associated with L-185.
Reduces interaction with VP16; when associated with L-189.
Reduces interaction with VP16; when associated with L-196.
Reduces interaction with VP16; when associated with L-200.
Reduces the formation of the TATA box-bound TBP ternary complex.
Associated with mild anemia and a tendency to iron loading. Prevents hepcidin/HAMP-induced degradation. Protects against severe malaria disease.
Complete loss of HAMP-dependent ubiquitination. Does not affect protein stability. Does not affect cell surface localization.
In HFE4; Does not affect protein stability. Does not affect cell surface localization. Increases iron export activity.
In HFE4; Reduces protein stability. Loss of cell surface localization. Loss of iron export activity. Increases intracellular manganese.
In HFE4; Reduces protein stability. Loss of cell surface localization. Loss of iron export function. Increases intracellular manganese.
Loss of iron export activity. Loss of cell surface localization. Increases intracellular manganese.
No loss of ubiquitination; when associated with R-236.
No loss of ubiquitination; when associated with R-253.
Reduces protein stability. Loss of cell surface localization. Loss of iron export activity. Increases intracellular manganese.
Abolishes localization to the nuclear membrane.
In EPM1B; affects interaction with REST.
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
In TEBIVANED1; results in severe early developmental defects when expressed in zebrafish embryos; results in defective cell cycle progression when expressed in zebrafish embryos.
In TEBIVANED2 and TEBIVANED3; unknown pathological significance; does not affect early development when expressed in zebrafish embryos.
In TEBIVANED2; results in severe early developmental defects when expressed in zebrafish embryos.
In TEBIVANED3; results in early developmental defects when expressed in zebrafish embryos.
In TEBIVANED4; results in early developmental defects when expressed in zebrafish embryos.
In TEBIVANED4; results in severe early developmental defects when expressed in zebrafish embryos.
Omega-N-methylarginine; by PRMT1; alternate
Symmetric dimethylarginine; by PRMT5 and PRMT7; alternate
TATA box binding protein associated factor (TAF) histone-like fold
(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Abolished E3 ubiquitin-protein ligase activity and ability to promote formation of the bacterial ubiquitin coat; when associated with A-885 and A-935.
Abolished E3 ubiquitin-protein ligase activity and ability to promote formation of the bacterial ubiquitin coat; when associated with A-885 and A-983.
Abolished E3 ubiquitin-protein ligase activity and ability to promote formation of the bacterial ubiquitin coat; when associated with A-935 and A-983.
Abolishes polyubiquitination activity of LUBAC; when associated with S-699.
Abolishes polyubiquitination activity of LUBAC; when associated with S-702.
Abolishes polyubiquitination activity of LUBAC; when associated with S-871.
Abolishes polyubiquitination activity of LUBAC; when associated with S-874.
Decreased ubiquitin-binding and ability to promote formation of the bacterial ubiquitin coat.
Does not affect interaction with OTULIN.
Reduced ubiquitination; when associated with R-735 and R-783.
Reduced ubiquitination; when associated with R-735 and R-875.
Reduced ubiquitination; when associated with R-783 and R-875.
Phosphoribosyltransferase domain-containing protein 1
Required for function in lipid remodeling
Increases NMD activity and translation stimulation.
Required for association with EIF4A3 and ECJ core components CASC3, MAGOH and RBM8A
In SPGF39; loss of the outer dynein arms in sperm cells.
In SPGF39; when associated in cis with L-3499; not expressed in flagellum and loss of the outer dynein arms in sperm cells when associated in cis with L-3499.
In SPGF39; when associated in cis with P-3595; not expressed in flagellum and loss of the outer dynein arms in sperm cells when associated in cis with P-3595.
Fibroblast growth factor-binding protein 1
Sufficient for interaction with FGF2 and FGF2-induced effects
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2, mitochondrial
In USH1G; atypical form with mild retinitis pigmentosa and normal vestibular function; also found in patients with autosomal recessive non-syndromic deafness; strongly reduced affinity for USH1C.
In USH1G; reduced interaction with IFT52 and IFT57.
Phosphomimetic mutant; does not affect interaction with MAGI2.
Probable disease-associated variant found in patients with non-syndromic sensorineural hearing loss; reduced interaction with IFT52 and IFT57; failure to rescue the USH1C splicing defect seen in USH1G-depleted cells.
Abolishes dimerization, leucine uptake and interaction with beta-1 integrins.
Amino acid transporter heavy chain SLC3A2
Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-365 Q-381 and Q-424.
Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-365 Q-381 and Q-506.
Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-365; Q-424 and Q-506.
Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-381; Q-424 and Q-506.
Interchain (with C-164 in SLC7A5; C-158 in SLC7A11 and C-154 in SLC7A8)
Nearly abolishes leucine transport activity.
No effect on dimerization, leucine uptake or interaction with beta-1 integrins.
Strongly decreased leucine transport activity.
Major facilitator superfamily domain-containing protein 3
Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5
Decrease in cytidine deaminase and antiviral activity.
Decrease in cytidine deaminase and antiviral activity; when associated with A-251.
Decrease in cytidine deaminase and antiviral activity; when associated with A-67.
No effect on cytidine deaminase and antiviral activity.
Resistant to HIV-1 Vif and abolishes Vif binding but is still efficiently incorporated into the virion.
Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion.
Resistant to HIV-1 Vif and reduces Vif binding.
Resistant to HIV-1 Vif, reduces Vif binding and abolishes incorporation into the virion.
In TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration.
In TDH4; strongly reduces activity; marginally respond to the increase of flavin mononucleotide concentration; reduces protein stability.
Decreased degradation in response to DNA damage. Decreased phosphorylation, degradation and increased interaction with RPL11 in response to DNA damage; when associated with A-233.
Decreased phosphorylation, degradation and increased interaction with RPL11 in response to DNA damage; when associated with A-289.
Loss of localization to the nucleolus and in response to DNA damage increased degradation and decreased interaction with RPL11; when associated with D-233.
Loss of localization to the nucleolus and in response to DNA damage increased degradation and decreased interaction with RPL11; when associated with D-289.
Mediates interaction with CDKN2A/isoform tumor suppressor ARF
Mediates interaction with human herpesvirus 8 protein ORF16
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8)
Largely reduces interaction with DDB1; abolishes interaction with DDB2.
Rho guanine nucleotide exchange factor 17
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 CMYP1A and MHS1; 2-3% of the cases; increases calcium-induced calcium release activity.
In CMYP1A and MHS1; 3-5% of the cases; increases calcium-induced calcium release activity.
In CMYP1A and MHS1; increases calcium-induced calcium release activity.
In CMYP1A 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 CMYP1A and MHS1; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR.
In CMYP1A; increases sensitivity to caffeine and 4-chloro-m-cresol.
In CMYP1A; 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 CMYP1A; unknown pathological significance.
In KDS; unknown pathological significance.
In MHS1, CMYP1A 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.
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.
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 MPLPF; no effect on localization; changed interaction with spliceosomal complexes.
In MPLPF; unknown pathological significance.
In MPLPF; unknown pathological significance; no effect on localization.
Probable ATP-dependent RNA helicase DDX41
In MTDPS3; significant reduction of activity.
In NCPH1; impairs adenosine triphosphate binding; reduction of activity.
Decreased function in regulation of alternative splicing. Decreased pre-mRNA binding. No effect on homodimerization.
Decreased function in regulation of alternative splicing. No effect on pre-mRNA binding.
Loss of function in regulation of alternative splicing. Loss of pre-mRNA binding activity. Decreased homodimerization.
Impaired substrate ubiquitination of both Tau and ATXN3.
Loss of predominant nuclear localization.
Loss of ubiquitination activity toward various substrates, including POLR2H, ATXN3, STUB1 and MAPT.
Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)
Mitochondrial import inner membrane translocase subunit Tim8 B
Cytochrome c oxidase assembly protein COX11, mitochondrial
In MC4DN23; unknown pathological significance; decreased respiration-derived ATP levels in patient cells.
Peptidase M1 membrane alanine aminopeptidase
Coiled-coil domain-containing protein 149
Interaction with FYN when phosphorylated at Tyr-284
In PTORCH3; increased cellular sensitivity to type IIFNs; fails to appropriately traffic USP18 thereby preventing USP18 to inhibit responses to IFN-I.
In PTORCH3; increased cellular sensitivity to type IIFNs; loss of interaction with USP18 thereby preventing USP18 to inhibit responses to IFN-I.
Prevents the nuclear import; when associated with A-374.
Prevents the nuclear import; when associated with A-375.
Prevents the nuclear import; when associated with A-409.
Prevents the nuclear import; when associated with A-415.
Reduces phosphorylation of STAT1 in response to IFN-ALPHA.
Signal transducer and activator of transcription 2
Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-442.
Does not interact with SLF1 and is defective in restoring cell survival after DNA damage; when associated with A-444.
Lower activity toward PCNA monoubiquitination.
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.
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like
Abolishes the basolateral membrane localization.
FERM and PDZ domain-containing protein 2
In NEDDSBA; results in loss of PI-specific phospholipase C sensitivity which could be rescued by expression of the wild-type protein.
Abscisic acid G-protein coupled receptor-like
Impaired amino-acid-mediated mTORC1 activation.
Impaired assembly of the GATOR2 complex.
Guanylate cyclase soluble subunit alpha-2
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.
Prevents phosphorylation and activation by STK11/LKB1 complex.
Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and RIOX1; when associated with A-56.
Abolishes histone H3K36me3-binding. Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and RIOX1; when associated with C-50.
Impairs chromatin binding as part of the PRC2 complex.
In muthPhf19; abolishes histone H3K36me3-binding and impaired activity of the PRC2 complex and subsequent H3K27me3 methylation.
Abolishes ceramide and phosphatidylcholine binding.
Conformation remains closed and prevents cytochrome c leakage.
Conformation remains open and constitutively allows cytochrome c efflux.
Involved in ceramide and phosphatidylcholine binding. Critical for channel structural stability and gating
Loss of PRKN-dependent monoubiquitination increases mitochondria calcium uptake, and ultimately increased apoptosis. Consequently, mitochondria are swelled with defective cristae structures. PRKN-dependent polyubiquitination is unaffected.
PRKN-dependent polybiquitination is decreased, whereas PRKN-dependent monoubiquitination, mitochondrial calcium uptake and apoptosis are unaffected; when associated with R-12; R-20 and 109-R-R-110.
PRKN-dependent polybiquitination is decreased, whereas PRKN-dependent monoubiquitination, mitochondrial calcium uptake and apoptosis are unaffected; when associated with R-12; R-20 and R-53.
PRKN-dependent polybiquitination is decreased, whereas PRKN-dependent monoubiquitination, mitochondrial calcium uptake and apoptosis are unaffected; when associated with R-12; R-53 and 109-R-R-110.
PRKN-dependent polybiquitination is decreased, whereas PRKN-dependent monoubiquitination, mitochondrial calcium uptake and apoptosis are unaffected; when associated with R-20; R-53 and 109-R-R-110.
Voltage-dependent anion-selective channel protein 1
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.
Dynein heavy chain domain-containing protein 1
Dynein heavy chain hydrolytic ATP-binding dynein motor region
In SPGF65; low expression, if any, in sperm flagella.
In SPGF65; unknown pathological significance.
In SPGF65; unknown pathological significance; low expression, if any, in sperm flagella.
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.
Found in a patient with early-onset atypical dystonia and myoclonic features; unknown pathological significance.
In AMC5; increased localization to the nuclear membrane; induces the formation of spheroid bodies in cells.
In DYT1 and AMC5; acts as a dominant negative; increased identical protein binding; loss of interaction with TOR1AIP1 and TOR1AIP2 with loss of ATPase activity induction; increased localization to the nuclear membrane; decreased ATP-dependent chaperone mediated protein folding; changed nuclear membrane organization.
In DYT1; increased identical protein binding; decreased ATP-dependent chaperone mediated protein folding; changed nuclear membrane organization.
In DYT1; increased identical protein binding; decreased ATP-dependent chaperone mediated protein folding; changed nuclear membrane organization; decreased neuron projection development.
Loss of ATP hydrolysis. Loss of interaction with KLHL14. Localizes in the nuclear envelope. No effect on interaction with TOR1AIP1.
Loss of ATP-binding. No effect on interaction with KLHL14. Increases interaction with TOR1AIP1 and TOR1AIP2. Abolishes interaction with SLC6A3.
N-linked (GlcNAc...) (high mannose) asparagine
Found in a case of clear cell renal carcinoma; somatic mutation.
Found in a endometrial cancer cell line.
Found in a malignant melanoma cell line.
Found in an endometrial cancer cell line.
Found in hematopoietic and lymphoid cancer cell lines.
Found in hematopoietic, lymphoid, lung and liver cancer cell lines.
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 7 and isoform 9.
Requires 2 nucleotide substitutions; found in a colon cancer cell line.
Acyl-CoA-binding domain-containing protein 7
3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic
Abolishes myristoylation and induces a subcellular location change.
In STHAGX1; decreased interaction with EDAR for isoform 1; decreased interaction with EDA2R for isoform 3; changed downstream signaling.
In XHED; abolishes proteolytic processing.
In XHED; decreased interaction with EDAR for isoform 1; decreased interaction with EDA2R for isoform 3; changed downstream signaling.
In XHED; loss of function in EDAR-mediated signaling; not secreted.
In XHED; loss of interaction with EDAR for isoform 1; decreased interaction with EDA2R for isoform 3; changed downstream signaling.
In XHED; unknown pathological significance.
In XHED; when associated in cis with C-290; loss of function in EDAR-mediated signaling when associated in cis with C-290; not secreted when associated in cis with C-290.
In XHED; when associated in cis with P-289; loss of function in EDAR-mediated signaling when associated in cis with P-289; not secreted when associated in cis with P-289.
4 X 7 AA repeats of P-[LV]-T-[IL]-T-[ST]-P
In CMD1OO; loss of DNA-binding transcription activator activity, RNA polymerase II-specific.
Epidermal growth factor receptor kinase substrate 8-like protein 3
In HYPT5; unknown pathological significance.
Found in a patient with familial intrahepatic cholestasis; unknown pathological significance.
Lipolysis-stimulated lipoprotein receptor
Abolishes ATPase activity, dominantly inhibits the TA protein insertion pathway.
In CMD2H; contrary to the wild type, the mutant is unable to rescue cardiac failure in zebrafish lacking GET3; results in decreased function in tail-anchored membrane protein insertion into ER membrane; has no effect on thermal stability.
In CMD2H; when associated in cis with 305-Q--Q-348 del.
In CMD2H; when associated in cis with variant W-289.
Cleavage; by S.Typhimurium viral protease GtgE
Loss of LRRK2 binding. Does not stimulate LRRK2 kinase activity. Localized to the cytosol.
Loss of phosphorylation by LRRK2. Does not stimulate LRRK2 kinase activity; when associated with E-71.
Loss of phosphorylation by LRRK2. Does not stimulate LRRK2 kinase activity; when associated with E-72.
Zinc finger CCCH domain-containing protein 11A
Suppression of NEDD8-binding; when associated with A-464; A-468 and A-587. Suppression of NEDD8-buster function; when associated with A-587.
Suppression of NEDD8-binding; when associated with A-464; A-468 and A-591. Suppression of NEDD8-buster function; when associated with A-591.
Abolishes inactivation of KCNMA1 channel.
Calcium-activated potassium channel subunit beta-2
Putative protein MSS51 homolog, mitochondrial
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
In GPHYSD3; unknown pathological significance; no effect on TGF-beta secretion.
Interchain (with C-33 in TGFB1); in linked form
Latent-transforming growth factor beta-binding protein 3
May be involved in congenital central hypoventilation syndrome.
Long-chain fatty acid transport protein 5
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1
In SPGF17; loss of function in egg activation.
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.
In MDBH; 50% reduction of cysteine-tRNA ligase activity.
In MDBH; 84% reduction of cysteine-tRNA ligase activity.
In MDBH; loss-of-function variant unable to rescue viability defects in a yeast complementation assay.
In MDBH; undetectable mutant protein in patient cells; loss-of-function variant unable to rescue viability defects in a yeast complementation assay.
Abolished RAC1 GTPase activity; when associated with A-566.
Abolished RAC1 GTPase activity; when associated with L-527.
In F-BARx-R5E mutant; abolished binding to membranes; when associated with 234--E--E-238.
In F-BARx-R5E mutant; abolished binding to membranes; when associated with 54-E-E-55.
Loss of the ability to stimulate cell migration, to localize at the plasma membrane protrusions and to dimerize.
SLIT-ROBO Rho GTPase-activating protein 2
Ubiquinone biosynthesis O-methyltransferase, mitochondrial
Interaction with the 5'-triphosphate group of PPP-RNA
Interferon-induced protein with tetratricopeptide repeats 1
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
No degradation; when associated with A-19.
No degradation; when associated with A-23.
Medium-chain acyl-CoA ligase ACSF2, mitochondrial
Iroquois-class homeodomain protein IRX-6
TRBP-interacting domain; interaction with STIL
Histone-lysine N-methyltransferase SETDB1
Calcium/calmodulin-dependent protein kinase II inhibitor 1
Phosphoserine; by PKC/PRKCE and PKC/PRKCZ
Reduces sensitivity to capsaicin 40-fold.
Required for PIP2-mediated channel inhibition
Transient receptor potential cation channel subfamily V member 1
4-hydroxybenzoate polyprenyltransferase, mitochondrial
In COQ10D1; decreased 4-hydroxybenzoate decaprenyltransferase activity.
In COQ10D1; decreased ubiquinone biosynthesis.
In COQ10D1; loss of ubiquinone biosynthesis.
In COQ10D1; unknown pathological significance.
In MSA1; associated with disease susceptibility.
In MSA1; associated with disease susceptibility; decreased ubiquinone biosynthesis.
ATP synthase F(0) complex subunit B1, mitochondrial
Completely abolishes enzyme activity. No change in subcellular location.
Phosphatidylcholine:ceramide cholinephosphotransferase 1
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.
Involved in interaction with pre-mRNA 5' splice site
Required for interaction with EFTUD2 and SNRNP200
Restriction endonuclease homology domain
Benign variant; originally reported as possible disease-causing mutation in a patient with hearing loss.
Found in a patient with hearing loss; unknown pathological significance.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-148.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-150.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-148 and A-150.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-111; A-146; A-148 and A-150.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-109; A-113; A-146; A-148 and A-150.
In KLHL20m6; abolishes interaction with CUL3; when associated with A-111; A-113; A-146; A-148 and A-150.
Zinc finger and BTB domain-containing protein 24
Opioid-binding protein/cell adhesion molecule
Fanconi anemia core complex-associated protein 100
Altered interaction with ARF1 and loss of association to membranes.
Loss of GTPase activity and loss of function.
C-terminal transmembrane transporter domain
Found in patients with recurrent kidney stones formation; unknown pathological significance; no effect on protein abundance; no effect on stability; decreased adenyl nucleotide antiporter activity; no effect on transporter activity regulation by calcium.
Mitochondrial adenyl nucleotide antiporter SLC25A25
Impairs DNA binding. Abolishes DNA binding; when associated with 52-A--A-57.
Impairs DNA binding. Abolishes DNA binding; when associated with 88-A--A-91.
Important for oligomerization and fiber formation
Loss of microtubule-end localization and microtubule plus-end tracking. Decreases MAPRE1 binding.
Found in a patient with Bardet-Biedl syndrome compound heterozygote for mutations in BBS1; rare variant; unknown pathological significance.
Found in a patient with Bardet-Biedl syndrome homozygous for a mutation in BBS2; unknown pathological significance.
Greatly decreases all interactions with BBS7, BBS9 and BBS12 indicating that this residue may be required for overall protein conformation rather than required for ATP binding and substrate folding.
In BBS10; has moderately reduced ability to interact with BBS7 and BBS9.
In BBS10; has moderately reduced ability to interact with BBS7 and BBS9; severely reduces the interaction with BBS12; 15% of wild-type.
In BBS10; has moderately reduced ability to interact with BBS7 and BBS9; severely reduces the interaction with BBS12; 19% of wild-type.
In BBS10; has moderately reduced ability to interact with BBS7 and BBS9; severely reduces the interaction with BBS12; 8% of wild-type.
In BBS10; unknown pathological significance.
Lymphocyte function-associated antigen 3
Pseudouridylate synthase RPUSD4, mitochondrial
80% decrease in interaction with MAPK1 and MAPK3.
Catalytically inactive and substrate trapping with higher affinity for substrate.
In a colon cancer sample; somatic mutation.
Receptor-type tyrosine-protein phosphatase eta
Substrate trapping with much higher affinity for substrate.
Abolishes binding of polyubiquitin to IKBKE.
Reduced higher order self-association and association with TRIM5.
Required for homodimerization and interaction with MTMR2
Glycoprotein integral membrane protein 1
4-aminobutyrate aminotransferase, mitochondrial
In GABATD; 25% reduction in 4-aminobutyrate aminotransferase activity.
Loss of 4-aminobutyrate aminotransferase activity.
N6,N6,N6-trimethyllysine; by EHMT2; alternate
N6,N6-dimethyllysine; by EHMT2; alternate
Pleckstrin homology domain-containing family A member 5
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.
In COQ10D6; unknown pathological significance.
Probable disease-associated variant found in patients with Schwannomatosis; loss of function.
Ubiquinone biosynthesis monooxygenase COQ6, mitochondrial
Pre-B-cell leukemia transcription factor 4
Minimal region required to interact with TAF12
Transcription initiation factor TFIID subunit 4
Binds actin 2.5-fold less than wild-type; little change in inhibition of actin polymerization.
Very weak actin binding; no inhibition of actin polymerization.
Found in a patient with developmental delay; unknown pathological significance; no effect on calcium ion export across plasma membrane.
In MRD66; decreased calcium ion export across plasma membrane.
In MRD66; decreased calcium ion export across plasma membrane; decreased localization to plasma membrane.
No effect on calcium ion export across plasma membrane.
Plasma membrane calcium-transporting ATPase 1
Required for basolateral membrane targeting
Killer cell lectin-like receptor subfamily F member 2
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.
Zinc-regulated GTPase metalloprotein activator 1A
Coiled-coil domain-containing protein 92
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.
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
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
In CSBS; affects subcellular location; the mutant protein is localized in the cytoplasm.
Abolishes insulin-induced tyrosine phosphorylation and insulin-induced receptor supersensitization.
Affects binding of catecholamines, and produces an uncoupling between the receptor and stimulatory G proteins.
Delayed agonist-promoted desensitization.
Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization.
Disruption of the cooperative binding of C-terminal peptides from FZD7 and phosphatidylinositol-4,5-bisphosphate.
Disruption of the cooperative binding of C-terminal peptides from FZD7 and phosphatidylinositol-4,5-bisphosphate. Impaired interaction with FZD7 and disruption of the cooperative binding of C-terminal peptides from FZD7 and phosphatidylinositol-4,5-bisphosphate; when associated with A-214.
Disruption of the cooperative binding of C-terminal peptides from FZD7 and phosphatidylinositol-4,5-bisphosphate. Impaired interaction with FZD7 and disruption of the cooperative binding of C-terminal peptides from FZD7 and phosphatidylinositol-4,5-bisphosphate; when associated with A-250.
Copper type II ascorbate-dependent monooxygenase C-terminal
Copper type II ascorbate-dependent monooxygenase N-terminal
Peptidyl-alpha-hydroxyglycine alpha-amidating lyase
Peptidyl-glycine alpha-amidating monooxygenase
Peptidylglycine alpha-hydroxylating monooxygenase
Electron transfer via tryptophanyl radical
Required for inhibition of CLOCK-BMAL1-mediated transcription
Breakpoint for translocation to form SET-CAN oncogene
Loss of membrane association and DLG2-binding.
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
N6,N6,N6-trimethyllysine; by METTL21A; in vitro
Reduces the pro-apoptotic activity and interaction with VDAC1.
Reduces the pro-apoptotic activity, no effect on interaction with VDAC1.
Transmembrane and coiled-coil domain-containing protein 5A
Elongation of very long chain fatty acids protein 4
Copper chaperone for superoxide dismutase
Found in a patient with congenital cataracts, hearing loss, neurodegeneration, neonatal hypotonia and hypoglycemia, pericardial effusion and neurodevelopmental regression after infection; the patient also carries a mutation in SLC33A1; mutant protein does not interact with SOD1.
Reduces copper binding by half; when associated with S-22. Negligible effect on zinc binding.
Reduces copper binding by half; when associated with S-244. Negligible effect on zinc binding.
Reduces copper binding by half; when associated with S-246. Negligible effect on zinc binding.
Reduces copper binding by half; when associated with S-25. Negligible effect on zinc binding.
In OCA1A and OCA1B; temperature sensitive variant.
Cyclin-dependent kinase 2-associated protein 1
Mitochondrial import inner membrane translocase subunit Tim17-A
Nuclear transcription factor Y subunit beta
Does not alter the enzymatic affinity of the corresponding enzyme; does not affect the affinity for single-stranded nucleic acid.
In LCA11; does not alter the enzymatic affinity of the corresponding enzyme; alters the affinity and/or the specificity of single-stranded nucleic acid.
In RP10; alters the affinity and/or the specificity of single-stranded nucleic acid.
In RP10; does not alter the enzymatic affinity of the corresponding enzyme; alters the affinity and/or the specificity of single-stranded nucleic acid.
Inosine-5'-monophosphate dehydrogenase 1
Breakpoint for translocation to form chimeric MASL1
Dominant negative effect on the ERK1/ERK2 signaling pathway and EPO-induced erythroid differentiation.
Malignant fibrous histiocytoma-amplified sequence 1
Ankyrin repeat domain-containing protein 11
In KBGS; unknown pathological significance.
Serine/threonine-protein phosphatase with EF-hands 1
Endosome/lysosome-associated apoptosis and autophagy regulator family member 2
(Microbial infection) Cleavage; S.pyogenes SpeB
Increased affinity for integrin ITGAV:ITGB3. Suppression of integrin binding; when associated with E-171; E-190 or E-204. Suppression of integrin binding; when associated with E-179 and E-181.
Involved in interaction with TMED10 C-terminus
Loss of activation by CASP1; when associated with A-116.
Loss of activation by CASP1; when associated with A-27.
No effect on binding to IL1R or on IL1B activity. Markedly reduced activity; when associated with E-171; E-190 and E-204. Markedly reduced activity; when associated with E-179; E-181; E-190 and E-204.
Promotes release of IL1B precursors through the Gasdermin-D (GSDMD) ring-shaped pore complex.
Suppression of integrin binding; when associated with E-179 and K-244. Markedly reduced activity; when associated with E-179; E-190; E-204 and C-233.
Suppression of integrin binding; when associated with E-181 and K-244. Markedly reduced activity; when associated with E-181; E-190; E-204 and C-233.
Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-171; E-190 and C-233. Markedly reduced activity; when associated with E-179; E-181; E-190 and C-233.
Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-171; E-204 and C-233. Markedly reduced activity; when associated with E-179; E-181; E-204 and C-233.
Suppression of integrin binding; when associated with K-244. Markedly reduced activity; when associated with E-190; E-204 and C-233.
Inhibits RHBDL4/RHBDD1-induced cleavage.
LHFPL tetraspan subfamily member 3 protein
Abolishes GTPase activity. No effect on GTP binding and on dimerization.
Impairs dimerization and abolishes GTPase activity. No effect on GTP binding.
Abolishes both enzymatic activity and effects on cell proliferation.
Ubiquitin carboxyl-terminal hydrolase 17
In SPG5A; unknown pathological significance.
Ubiquitin carboxyl-terminal hydrolase 43
Torsin-1A-interacting protein 2, isoform IFRG15
In EDSVASC; requires 2 nucleotide substitutions.
In PMGEDSV; does not affect interaction with ADGRG1.
O-linked (Gal...) hydroxylysine; alternate
14-3-3 protein gamma, N-terminally processed
Found in an individual with autism; unknown pathological significance.
In DEE56; unknown pathological significance.
N-acetylmethionine; in 14-3-3 protein gamma; alternate; partial
N-acetylvaline; in 14-3-3 protein gamma, N-terminally processed; partial
Probable disease-associated variant found in an individual with neurodevelopmental disorder.
Decreased interaction with nuclear receptors.
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.
Nuclear envelope phosphatase-regulatory subunit 1
Decreases 3-alpha-hydroxysteroid reductase activity about 50-fold.
Decreases 3-alpha-hydroxysteroid reductase activity about 500-fold.
Increases the low androstenedione reductase activity.
Strongly decreases affinity for androstenedione. Decreases androstenedione reductase activity about 60-fold.
In HMN6; does not affect ATPase activity; loss of helicase activity on RNA duplices.
In HMN6; does not affect activity; reduces protein steady-state levels.
In HMN6; severe reduction of ATPase activity and loss of helicase activity on RNA duplices.
In HMN6; unknown pathological significance.
Affects ion selectivity of the channel. Reduced permeability to negatively charged glutamate and gluconate.
Volume-regulated anion channel subunit LRRC8D
Leucine-rich repeat-containing protein 36
In GSD4; childhood neuromuscular form; 15 to 25% residual activity.
In GSD4; non-progressive form; impairs protein stability; 50% residual activity.
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.
FHF complex subunit HOOK-interacting protein 2B
Loss of DNA polymerase activity; when associated with A-199.
Loss of DNA polymerase activity; when associated with D-198.
Impaired import of NAD(+) into mitochondria.
Mitochondrial nicotinamide adenine dinucleotide transporter SLC25A51
MORC family CW-type zinc finger protein 4
Subject to oxidation and hydroselenide loss to dehydroalanine
Found in a patient with primary ovarian failure associated with intellectual disability and sensorineural hearing loss; unknown pathological significance; no change in glycosylation pattern.
Impaired glycosylation. Loss of GLY1 and GLY2 forms. No effect on oocyte survival.
Impaired glycosylation; loss of GLY2 form; oocyte death.
In OZEMA7; impaired glycosylation resulting in the absence of GLY2 and the accumulation of GLY1 forms; associated with increased hemi-channel activity.
In OZEMA7; impaired glycosylation resulting in the absence of GLY2 and the accumulation of GLY1 forms; associated with increased hemichannel activity.
Zinc fingers and homeoboxes protein 1, isoform 2
Abolishes phosphorylation. Reduces COS cell adhesion to ICAM1.
Phosphothreonine; by PKC/PRKCA; in vitro
in ADMIDAS binding site and liganded-open conformation
in ADMIDAS binding site and unliganded-closed conformation
In MCPH20; Decreased expression at the mRNA level and loss of localization at the midbody during cytokinesis and consequently loss of CIT/CRIK recruitment to the midbody, when analyzed in primary fibroblasts from a patient who is a compound heterozygous with variant D-849.
In MCPH20; Decreased expression at the mRNA level and loss of localization at the midbody during cytokinesis and consequently loss of CIT/CRIK recruitment to the midbody, when analyzed in primary fibroblasts from a patient who is a compound heterozygous with variant V-1221.
In MCPH20; drastically decreased expression at the mRNA level; loss of localization at the midbody during cytokinesis and consequently loss of CIT/CRIK recruitment to the midbody.
In MCPH20; unknown pathological significance.
Required for microtubule-binding with high affinity
In GSD12; likely benign variant; does not affect thermal stability; 4-fold decrease in catalytic efficiency due to reduced enzyme activity.
In GSD12; reduces thermal stability; 3-fold decrease in catalytic efficiency mostly due to reduced substrate affinity.
Necessary for preference for fructose 1,6-bisphosphate over fructose 1-phosphate
Schiff-base intermediate with dihydroxyacetone-P
Sprouty-related, EVH1 domain-containing protein 3
Fails to restore protein stability; when associated with pathogenic variant BBS9 R-141.
In BBS9; severe loss of protein stability, probably due to aberrant folding.
Gamma-aminobutyric acid receptor subunit alpha-5
In DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway.
In DEE79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway; the mutant subunit decreases the trafficking of the partnering GABRB3 subunit to the cell membrane with no effect on other subunits.
In DEE79; increased affinity to GABA; decreased maximal GABA-evoked current density.
In colon cancer; sporadic; somatic mutation; loss of ligand-binding.
In colon cancer; sporadic; somatic mutation; partial loss of ligand-binding.
Peroxisome proliferator-activated receptor gamma
Significant independent determinant of CIMT; may protect from early atherosclerosis in subject at risk for diabetes; associated with BMI.
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.
Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole
Does not result in actin depolymerization activity in absence of calcium. Has actin depolymerization activity in absence of calcium; when associated with N-214 and N-697 or N-214, N-697 and Q-719.
Does not result in actin depolymerization activity in absence of calcium. Has actin depolymerization activity in absence of calcium; when associated with N-214 and N-697 or N-214, Q-236 and N-697.
Does not result in actin depolymerization activity in absence of calcium. Has actin depolymerization activity in absence of calcium; when associated with N-214 and Q-236, N-214 and Q-719 or N-214, Q-236 and Q-719.
In AMYL5; does not result in actin depolymerization in absence of calcium.
5'-AMP-activated protein kinase subunit beta-1
Abolishes myristoylation and AMP-enhanced phosphorylation of PRKAA1 or PRKAA2.
Loss of activity; when associated with Q-36.
Loss of activity; when associated with S-34.
Doublesex- and mab-3-related transcription factor B1
Histone-lysine N-methyltransferase SETDB2
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B
In PPNAD3; shows significantly higher cyclic AMP levels after transfection with the mutant protein than after transfection with the wild-type, indicating an impaired ability of the mutant protein to degrade cAMP.
Cleavage; by caspase-3, caspase-6 and caspase-7
4 X 17 AA approximate tandem repeats of P-G-P-R-G-E-A-G-G-Q-A-E-A-[KR]-G-D-A
Cell growth regulator with EF hand domain protein 1
Eukaryotic translation initiation factor 3 subunit B
In SCA23; PDYN, dynorphin A and dynorphin B are located in Purkinje cells as observed in control cerebellum, but cerebellar tissue with the mutation has decreased levels of SLC1A6 and CALB1, both of which are markers of Purkinje cells; SLC1A6 accumulates and aggregates in patient cerebellar tissue.
In SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, resulting in an approximately 2-fold decreased level of dynorphin B compared to dynorphin A; mutant dynorphin A is neurotoxic to cultured striatal neurons, suggesting a dominant-negative effect; disrupts membrane property.
In SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, with increased levels of dynorphin A compared to dynorphin B; mutant dynorphin A is neurotoxic to cultured striatal neurons, suggesting a dominant-negative effect; disrupts membrane property.
In SCA23; the mutant PDYN protein is produced, but processing to opioid peptides is dramatically affected, with increased levels of dynorphin A compared to dynorphin B; these results suggest slow conversion of dynorphin A to short enkephalins; mutant S-211 dynorphin A is not neurotoxic to cultured striatal neurons; no effect on membrane property.
Constitutively active. Dramatic reduction of the rate of GTP hydrolysis. Loss of interaction with AFDN, RLF and RALGDS; when associated with S-53. Loss of interaction with AFDN; when associated with G-55.
Dominant negative. Loss of interaction with AFDN, RLF and RALGDS.
In NS8; results in increased ELK1 transcriptional activation.
In NS8; results in increased ELK1 transcriptional activation; results in increased MAPK-ERK signaling.
In NS8; results in increased MAPK-ERK signaling.
Loss of interaction with AFDN, RLF and RALGDS; when associated with L-79.
Loss of interaction with AFDN, but not with RLF and RALGDS; when associated with L-79.
Probable disease-associated variant found in patients with features of Noonan syndrome.
No effect on catalytic activity. No effect on catalytic activity; when associated with D-76.
No effect on catalytic activity; when associated with D-145.
Complement C1q tumor necrosis factor-related protein 8
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.
In COXPD15 and MC1DN27; decreased methionyl-tRNA formyltransferase activity.
In COXPD15; loss of methionyl-tRNA formyltransferase activity.
Methionyl-tRNA formyltransferase, mitochondrial
In EPM12; due to a nucleotide substitution that can result in aberrant splicing; patient cells contain both normally spliced transcripts and transcripts that retained intron 1; marked reduction of protein expression in patient cells.
Probable RNA polymerase II nuclear localization protein SLC7A6OS
Required for nuclear and nucleolar localization
Activated RNA polymerase II transcriptional coactivator p15
Transcriptional coactivator p15 (PC4) C-terminal
Histidine-rich carboxyl terminus protein 1
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)
High affinity immunoglobulin epsilon receptor subunit gamma
EP300-interacting inhibitor of differentiation 2
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.
In MYP26; unknown pathological significance.
Membrane-spanning 4-domains subfamily A member 5
Decreased association with 'Lys-48'-linked conjugated ubiquitin.
Decreased binding to 'Lys-48' tetraubiquitin chains.
Greatly impairs ubiquitin hydrolase activity.
Loss of binding to 'Lys-48' tetraubiquitin chains.
No effect on binding to 'Lys-48' tetraubiquitin chains.
Ubiquitin carboxyl-terminal hydrolase MINDY-1
Acyl-coenzyme A synthetase ACSM1, mitochondrial
Alkyldihydroxyacetonephosphate synthase, peroxisomal
In RCDP3; does not affect protein levels.
In RCDP3; severely reduced protein levels.
Apolipoprotein L domain-containing protein 1
Decreases the vesicular uptake of noradrenaline and dopamine.
Decreases the vesicular uptake of noradrenaline, dopamine and serotonin; may predispose carriers to a increased cortical response to negative stimuli and reduced threat-related amygdala reactivity.
Found in a patient with bipolar disorder; decreases the vesicular uptake of noradrenaline, dopamine and serotonin.
Found in a patient with bipolar disorder; has no significant effect on monoamine vesicular uptake.
Found in patients with bipolar disorder; decreases the vesicular uptake of noradrenaline, dopamine and serotonin.
Found in patients with bipolar disorder; increases the vesicular uptake of noradrenaline and dopamine.
Complete loss of interaction with IRF3. About 3-4 times less genomic RNA in West Nile virus particles.
Probable ATP-dependent RNA helicase DDX56
Abrogates transcriptional activation and RNA polymerase II binding by the MTAD region. No change in ATP binding and ATPase activities.
Abrogates transcriptional activation by the MTAD region. No change in RNA polymerase II holoenzyme binding.
Does not inhibit binding to origins of DNA replication.
Does not inhibit binding to origins of DNA replication; when associated with A-511.
Does not inhibit binding to origins of DNA replication; when associated with A-512.
Does not reduce siRNA-binding and interaction with AGO2.
Inhibits interaction with AGO2, DICER1 and TARBP2. Abrogates helicase activity and transcriptional activation. Does not inhibit binding to origins of DNA replication.
Inhibits siRNA-binding and decreases interaction with AGO2; when associated with A-53 and A-54.
Inhibits siRNA-binding and decreases interaction with AGO2; when associated with A-53 and A-55.
Inhibits siRNA-binding and decreases interaction with AGO2; when associated with A-54 and A-55.
Inhibits siRNA-binding and interaction with AGO2.
Inhibits siRNA-binding and interaction with AGO2; when associated with A-234 and A-235.
Inhibits siRNA-binding and interaction with AGO2; when associated with A-234 and A-236.
Inhibits siRNA-binding and interaction with AGO2; when associated with A-235 and A-236.
Localizes in the cytoplasm and does not interact with the importin complex.
Localizes in the nucleus and interacts with the importin complex.
Localizes in the nucleus and the cytoplasm and interacts weakly with the importin complex.
Necessary for interaction with RNA polymerase II holoenzyme
Reduces NUP98-induced mRNA transcription and alternative splicing activities.
Reduces siRNA-binding and interaction with AGO2.
Reduces siRNA-binding and interaction with AGO2; when associated with A-186.
Reduces siRNA-binding and interaction with AGO2; when associated with A-187.
Reduces siRNA-binding and interaction with AGO2; when associated with A-6.
Reduces siRNA-binding; when associated with A-5.
Abolished acetylation by EP300. Abolished deacetylation by SIRT6.
Abolished interaction with phosphorylated CTNNB1. Impaired phosphorylation of histone H3.
Abolishes both pyruvate kinase and protein kinase activities.
Abolishes serine binding and allosteric activation.
Impaired homotetramerization, leading to homodimerization and subsequent activation of the protein kinase activity.
Mimics acetylation, promoting homodimerization and ativation of the protein kinase activity.
Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-403.
Significant reduction in hydroxylation and in PKM-mediated transcriptional activity of HIF1A; when associated with A-408.
Unable to bind FBP but still activated by serine.
Benign variant; no effect on PYCARD/ASC inflammasome formation.
Does not form MEFV- and PSTPIP1-containing perinuclear specks.
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 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 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.
Required for homotrimerization and induction of pyroptosomes
Essential for protaglandin-E synthase activity
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.
T-cell receptor-associated transmembrane adapter 1
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)
Loss of acetylation and transcriptional coactivator activity. Reduced ubiquitination. Significant reduction in ubiquitination; when associated with A-182.
Reduced sumoylation and transcriptional corepressor activity.
Reduced ubiquitination. Significant reduction in ubiquitination; when associated with A-626.
SUMO interaction motif 1 (SIM); crucial for efficient sumoylation
Significant loss of interaction with SUMO1 and SUMO2 and reduced transcriptional corepressor activity.
Immunoglobulin superfamily DCC subclass member 4
Involved in retention in extracellular matrix (ECM); involved in trimer formation
Reduces attachment to cells and retention in extracellular matrix (ECM); retention in ECM partially dependent on beta-1 integrin.
Reduces attachment to cells and retention in extracellular matrix.
No effect on basal enzyme activity, but increased enzyme activity upon activation via G-proteins or forskolin.
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.
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.
Glutamate receptor ionotropic, kainate 3
Abolishes inositol-4,5-bisphosphate binding. Strongly reduces affinity for inositol-3,4,5-trisphosphate.
Found in a clear cell renal carcinoma case; somatic mutation.
Found in a patient with global developmental delay; unknown pathological significance.
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.
Breakpoint for translocation to form NUP98-PHF23 oncogene
Centrosomal protein of 290kDa coiled-coil region
In LCA10; also found in a patient with night blindness and hearing loss.
In LCA10; unknown pathological significance.
In MKS4; unknown pathological significance.
Self-association (with itself or C-terminus)
Self-association (with itself or N-terminus)
Epithelial cell-transforming sequence 2 oncogene-like
Deamidated glutamine; by Photorhabdus PAU_02230
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.
Cellular retinoic acid-binding protein 1
In isoform 2, isoform 3, isoform 4, isoform 5 and isoform 6.
In isoform 3, isoform 4, isoform 5 and isoform 6.
TOX high mobility group box family member 4
Decreased interaction with HUWE1. Loss of oligomerization. Increased proteasomal degradation. Loss of stabilization by HAPSTR2.
HUWE1-associated protein modifying stress responses 1
HUWE1-binding and HAPSTR1 oligomerization (HBO) domain
Loss of interaction with HUWE1. No effect on oligomerization.
Loss of interaction with HUWE1. No effect on oligomerization. No effect on stabilization by HAPSTR2.
In DEE102; unknown pathological significance.
Modulates L-glutamine-induced conductances and Na(+) binding
Sodium-coupled neutral amino acid transporter 3
Abolished E3 ubiquitin-protein ligase activity in vitro.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-37.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-40.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-54.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-57.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-72.
Abolishes ability to regulate T-cell activation and E3 ligase activity in vitro; when associated with A-75.
Abolishes ability to regulate T-cell activation but not E3 ligase activity in vitro. Also abolishes myristoylation and membrane localization.
Interaction with the C2HC RNF-type zinc finger
Interaction with the RING-type zinc finger
Reduced ubiquitination and reduced binding to ubiquitinated proteins; when associated with P-217.
Reduced ubiquitination and reduced binding to ubiquitinated proteins; when associated with Q-221.
Required for interaction with ubiquitin and for autoubiquitination
Cilia- and flagella-associated protein 44
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.
High mobility group nucleosome-binding domain-containing protein 4
Abolishes interaction with SARS-CoV spike glycoprotein.
About 50% loss of angiotensin I cleavage but two-fold greater activity with angiotensin II.
About 80% loss of angiotensin I cleavage.
About 95% loss of angiotensin I cleavage.
Complete loss of enzyme activity. Does not affect amino acid transport activity of SLC6A19.
Essential for cleavage by TMPRSS11D and TMPRSS2
Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein.
Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and L-386.
Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and Y-330.
Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-330 and L-386.
Increases very slightly the interaction with RBD domain of SARS-CoV-2 spike protein.
Inhibits interaction with SARS-CoV spike glycoprotein.
Interaction with SARS-CoV spike glycoprotein
No effect on interaction with SARS-CoV spike glycoprotein.
Processed angiotensin-converting enzyme 2
Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Strongly inhibits interaction with SARS-CoV spike glycoprotein.
In AMS; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type.
In BBRSAY; decreased chromatin binding; the mutant binds to alternative chromatin binding sites compared to wild-type.
N-linked (GlcNAc...) (complex) asparagine; alternate
N-linked (GlcNAc...) (paucimannose) asparagine; alternate
No effect on proteolytic processing, enzyme activation or sorting to cytoplasmic granules.
Does not interact with AKAP9 and the kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with L-602.
Does not interact with AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1); when associated with I-609.
Has a voltage-gated potassium channel activity. Disrupts KCNE4-mediated voltage-gated potassium channel activity inhibition.
Has a voltage-gated potassium channel activity. Inhibition of voltage-gated potassium channel activity by KCNE4.
Helical; Voltage-sensor; Name=Segment S4
In JLNS1 and LQT1; impairs outward potassium current; affects plasma membrane localization.
In JLNS1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers).
In JLNS1; requires 2 nucleotide substitutions; does not affect plasma membrane localization; complete loss of outward currents; enhances outward currents when coexpressed with wild type at equimolar ratio.
In LQT1 and JLNS1; affects plasma membrane localization; strongly reduces potassium current; impairs binding to AKAP9 and the targeting protein kinase A (PKA) catalytic subunit and protein phosphatase 1 (PP1).
In LQT1 and JLNS1; impairs outward potassium current; affects plasma membrane localization.
In LQT1; affects channel activity; when expressed in heterologous system the mutant significantly reduces total IKs steady-state and tail currents with a positive shift of the voltage dependence of activation.
In LQT1; associated with M-254 in a patient.
In LQT1; associated with M-417 in a patient.
In LQT1; associated with a fruste phenotype; decreases interaction with KCNE1 C-terminus; does not affect plasma membrane localization; reduces IKS current density; shifts activation of the voltage dependence; deactivates more rapidly; impairs binding with phosphatidylinositol 4,5-bisphosphate.
In LQT1; complete loss of outward potassium current when expressed alone and even in the presence of the wild type at variable ratios; decreases plasma membrane localization.
In LQT1; complete loss of outward potassium current; enhances outward potassium current when co-transfected with wild type; decreases plasma membrane localization.
In LQT1; decreases IKs amplitude; accelerates the IKs deactivation; effect on plasma membrane localization; reduces up-regulation of Iks through PKA activation.
In LQT1; decreases delayed rectifier potassium current Iks; prevents the up-regulation of Iks through PKA activation.
In LQT1; decreases interaction with KCNE1 C-terminus; does not affect plasma membrane localization; reduces IKS current density; impairs binding with Phosphatidylinositol 4,5-bisphosphate.
In LQT1; decreases interaction with KCNE1 C-terminus; does not affect plasma membrane localization; reduces IKS current density; impairs binding with phosphatidylinositol 4,5-bisphosphate; loss of channel activity.
In LQT1; decreases outward potassium current; decreases plasma membrane localization.
In LQT1; functional channel with reduced macroscopic conductance (homomultimers); alteration of normal KVLQT1 function (mut/wt homomultimers).
In LQT1; loss of channel activity and no interaction with wt KVLQT1 or MINK subunits.
In LQT1; loss of function mutation acting in a dominant-negative manner.
In LQT1; minor changes of wt current (homomultimers); positive voltage shift of the channel activation (heteromultimers).
In LQT1; no effect on cell membrane localization; slows activation kinetics; accelerates deactivation kinetics; rightshifts the voltage-dependent activation; does not affect cAMP-dependent up-regulation; decreases interaction with KCNE1 C-terminus; does not affect plasma membrane localization; does not affect phosphorylation at S-27 during cAMP-dependent stimulation; reduces IKS current density; impairs binding with Phosphatidylinositol 4,5-bisphosphate.
In LQT1; reduces IKs density and causes a right-shift of the current?voltage relation of channel activation; reduces cell surface expression; no effect on interaction with AKAP9; does not affect the cAMP-dependent IKs up-regulation.
In LQT1; slower rate of activation and voltage dependence of activation-inactivation shifted to more positive potentials (homomultimers); channels non-functional (heteromultimers).
In LQT1; unknown pathological significance.
In LQT1; unknown pathological significance; hardly any effect on channel activity, shows fast activation.
In LQT1; unknown pathological significance; no effect on channel activity.
Inhibits voltage-gated potassium channel activity.
Interaction with CALM; calcium-dependent
No phosphorylation by PKA. Decreases delayed rectifier potassium channel activity.
Potassium channel voltage dependent KCNQ C-terminal
Potassium voltage-gated channel subfamily KQT member 1
Reduced cell surface expression and moderately reduced potassium current.
Reduced cell surface expression and strongly reduced potassium current.
Reduced protein expression, probably due to misfolding and proteasomal degradation. No detectable electrophysiological activity. Reduced electrophysiological activity in the presence of KCNE1.
Reduced protein expression, probably due to misfolding and proteasomal degradation. Significantly reduced electrophysiological activity. Reduced electrophysiological activity in the presence of KCNE1.
Strongly inhibits SLC5A3 transporter activity.
Mitochondrion outer membrane (MOM)-targeting sequence
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.
Phosphoserine; by GSK3-alpha and GSK3-beta
Gamma-aminobutyric acid receptor subunit rho-1
In JBTS33; loss of function in ciliogenesis.
Mediates modulation of Th2 dominant cytokine production
Probable disease-associated variant found in patients with microcephaly and intellectual disability; disrupts interaction with CEP63; no effect on interaction with PCM1.
5'-nucleotidase domain-containing protein 1
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.
Pregnancy-specific beta-1-glycoprotein 4
In IMD8; the mutation causes a decrease in protein stability; patient T-cell blasts show delayed activation of signaling molecules MAPK3 and MAPK1.
Almost complete loss of bactericidal activity.
WD repeat and HMG-box DNA-binding protein 1
Beta-1,4 N-acetylgalactosaminyltransferase 1
50% decrease in scramblase activity in presence of Ca2+, and 40% decrease in scramblase activity in presence of Mg2+.
Important for degradation of atrial natriuretic peptide by IDE
No effect on degradation of atrial natriuretic peptide by IDE.
Reduced degradation of atrial natriuretic peptide by IDE; when associated with N-147--151-YDEL.
Reduced degradation of atrial natriuretic peptide by IDE; when associated with S-124--126-RDEL.
Reduced binding to THRB, RXRA, ESR2 and ESR1.
Strong increase in binding to THRB, RXRA and ESR2, but dramatic decrease in binding to ESR1.
Interferon-induced transmembrane protein 10
ATP-dependent zinc metalloprotease YME1L1
In OPA11; does not affect localization to mitochondria; abolishes processing to mature form by MPP; results in decreased mitochondrial protein catabolism; has very low protease activity; results in mitochondrial fragmentation.
Loss of ATPase and protease activity. Loss of PRELID1 degradation. Cannot restore OMA1 degradation in YME1L-depleted cells.
Loss of protease activity. Cannot restore OMA1 degradation in YME1L-depleted cells.
Required for interaction with YY1, SIN3A and HDAC1, and transcriptional repression activity
Coiled-coil domain-containing protein 102B
Required for centriolar localization and for interaction with CEP250, CROCC, LRRC45 and NEK2
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-135, A-142, A-194, A-210, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-142, A-194, A-210, A-401 and A-404.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-142, A-194, A-210, A-401 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-142, A-194, A-210, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-142, A-194, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-142, A-210, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-135, A-194, A-210, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-22, A-34, A-142, A-194, A-210, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-21, A-34, A-135, A-142, A-194, A-210, A-401, A-404 and A-406.
Substantial decrease in phosphorylation; when associated with A-22, A-34, A-135, A-142, A-194, A-210, A-401, A-404 and A-406.
Mitochondrial coiled-coil domain protein 1
Coiled-coil domain-containing protein 178
Tubulin-specific chaperone cofactor E-like protein
Decrease in AURKB activity and almost no phosphorylation by TTK; when associated with A-88; A-169 and A-230.
Decrease in AURKB activity and almost no phosphorylation by TTK; when associated with A-88; A-94 and A-230.
Decrease in AURKB activity and almost no phosphorylation by TTK; when associated with A-94; A-169 and A-230.
Decrease in AURKB activity and dimer disruption. Decrease in AURKB activity and almost no phosphorylation by TTK; when associated with A-88; A-94 and A-230.
Decrease in AURKB activity and no effect on the structure.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-171, A-185, A-189, A-199 and A-204.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-171, A-185, A-189, A-199 and A-219.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-171, A-185, A-189, A-204, A-219.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-171, A-185, A-199, A-204 and A-219.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-171, A-189, A-199, A-204 and A-219.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-106, A-185, A-189, A-199, A-204 and A-219.
Decreases interaction with SOG1 and SOG2, abolishes localization to centromeres in prometaphase; when associated with A-171, A-185, A-189, A-199, A-204 and A-219.
Fails to exhibit normal localization to the nucleolus in interphase depleted cells.
Loss of binding to BIRC5; when associated with E-70.
Loss of binding to BIRC5; when associated with E-74.
Loss of binding to INCENP; when associated with E-35.
Loss of binding to INCENP; when associated with Y-46.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with E-17 and E-19.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with E-17 and E-20.
Loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with E-19 and E-20.
Required for interaction with INCENP and BIRC5
Required to form a minimal CPC core complex that localizes to the central spindle and midbody and properly executes the role of the CPC during cytokinesis
Results in reduction but not abolition of phosphorylation.
Glycosyltransferase 1 domain-containing protein 1
GDP-locked form; mild defects in ciliary assembly. Loss of interaction with the intraflagellar transport (IFT) complex B via the IFT74-IFT81 heterodimer. Loss of interaction with CEP19. Loss of localization to the centrosome. Loss of localization to the base of the cilium.
GTP-locked form; interacts with the intraflagellar transport (IFT) complex B via the IFT74-IFT81 heterodimer. Localizes to the base of the cilium and accumulates within the cilium and at the tip in specific puncta.
Mild defects in ciliary assembly. Loss of interaction with the intraflagellar transport (IFT) complex B via the IFT74-IFT81 heterodimer. Interacts with CEP19.
Chloride intracellular channel protein 3
Required for insertion into the membrane
Neuroblast differentiation-associated protein AHNAK
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.
In SEDKF; unknown pathological significance.
Membrane-bound transcription factor site-1 protease
Essential for phosphatidylinositol-4-phosphate phosphatase activity
Loss of phosphatidylinositol-4-phosphate phosphatase activity.
Neurotrophin receptor-interacting factor homolog
Peroxisomal N(1)-acetyl-spermine/spermidine oxidase
Nitration by tetranitromethane destroys a Ca(2+) binding site and inactivates enzyme
Oncostatin-M-specific receptor subunit beta
In LAD3; unknown pathological significance; decreases cell adhesion in hematopoietic cells; requires 2 nucleotide substitutions.
Cancer/testis antigen family 45 member A2
Cancer/testis antigen family 45 member A8
Cancer/testis antigen family 45 member A9
Abolishes activity as transcriptional activator.
Altered sequence specificity, with increased affinity for the DNA sequence 5'-TAATCTAATTA-3'.
Decreased activity as transcriptional activator.
Important for transcriptional activation of target genes
Loss of interaction with EP300 and CREBBP.
No effect on activity as transcriptional activator.
Reduced activity as transcriptional activator.
Required for interaction with EP300 and CREBBP, and for transcriptional activation of target genes
Found in a patient with neural tube defects; unknown pathological significance.
In OTFCS2; significantly reduced transactivation of the regulatory sequence of NKX3-2 in cells over-expressing the mutant sequence compared to cells over-expressing wild-type sequence.
Abolishes binding to GTP and GTPase activity; when associated with A-290.
Abolishes binding to GTP and GTPase activity; when associated with A-292.
In MMAA; abolishes protein levels; decreases protein stability.
In MMAA; decreases protein levels; decreases protein stability; no effect on binding to GDP; no effect on GTPase activity; no effect on interaction with MUT; impairs GTPase activity stimulation by MUT; reduces release of AdoCbl by MMAB.
In MMAA; decreases protein levels; highly decreases binding to GDP; no effect on GTPase activity; abolishes interaction with MUT; impairs GTPase activity stimulation by MUT; highly reduces release of AdoCbl by MMAB.
In MMAA; decreases protein levels; no effect on binding to GDP; decreases by 55% GTPase activity; abolishes interaction with MUT; impairs GTPase activity stimulation by MUT; highly reduces release of AdoCbl by MMAB.
In MMAA; decreases protein levels; no effect on binding to GDP; no effect on GTPase activity; abolishes interaction with MUT; impairs GTPase activity stimulation by MUT; highly reduces release of AdoCbl by MMAB.
In MMAA; decreases protein levels; no effect on binding to GDP; no effect on GTPase activity; no effect on interaction with MUT; impairs GTPase activity stimulation by MUT; reduces release of AdoCbl by MMAB.
In MMAA; decreases protein levels; no effect on binding to GDP; no effect on GTPase activity; no effect on interaction with MUT; impairs GTPase activity stimulation by MUT; slightly reduces release of AdoCbl by MMAB.
In MMAA; highly decreases protein levels.
In MMAA; highly decreases protein levels; decreases protein stability.
In MMAA; highly decreases protein levels; decreases protein stability; no effect on binding to GDP; no effect on GTPase activity; abolishes interaction with MUT; impairs GTPase activity stimulation by MUT; highly reduces release of AdoCbl by MMAB.
In MMAA; no effect on protein levels; no effect on binding to GDP; no effect on GTPase activity; abolishes interaction with MUT; impairs GTPase activity stimulation by MUT; highly reduces release of AdoCbl by MMAB.
In MMAA; no effect on protein levels; no effect on binding to GDP; no effect on GTPase activity; no effect on interaction with MUT; impairs GTPase activity stimulation by MUT; reduces release of AdoCbl by MMAB.
In MMAA; unknown pathological significance; decreases protein levels; no effect on binding to GDP; no effect on GTPase activity; no effect on interaction with MUT; impairs GTPase activity stimulation by MUT; reduces release of AdoCbl by MMAB.
Methylmalonic aciduria type A protein, mitochondrial
U3 small nucleolar RNA-associated protein 14 homolog C
(Microbial infection) Interaction with Tula hantavirus
BMP-binding endothelial regulator protein
Hsp90 co-chaperone Cdc37, N-terminally processed
N-acetylvaline; in Hsp90 co-chaperone Cdc37, N-terminally processed
Motor neuron and pancreas homeobox protein 1
Increased permeability to glycerol at acidic pH.
Nearly abolishes permeability to glycerol.
Glycylpeptide N-tetradecanoyltransferase 2
Glycylpeptide N-tetradecanoyltransferase C-terminal
Glycylpeptide N-tetradecanoyltransferase N-terminal
Abolishes phosphorylation. Abolishes interaction with PIN1. Reduces protein stability.
Cis/trans isomerization of proline peptide bond; by PIN1; dependent on Ser-110 phosphorylation
Interleukin-1 receptor-associated kinase 3
May be associated with ASRT5; abolishes phosphorylation of Ser-110; abolishes interaction with PIN1; no effect on cytoplasmic localization; reduces protein stability.
Phosphomimic. Slight decrease in the interaction with PIN1. Weak interaction with PIN1 in absence of IL33-mediated dendritic cell stimulation. Increases resistant to degradation. Localizes to the nucleus in absence of stimulus. Does not affect isomerization of Pro-111 peptide bond.
No effect on keratin filament organization.
Phosphoserine; by MAPKAPK2, MAPKAPK3 and PKC
In XLID96; unknown pathological significance.
Loss of TGF-beta-induced apoptosis. No translocation to the nucleus following TGF-beta treatment. Loss of XIAP-binding.
Abolishes guanyl nucleotide exchange activity toward RHOA.
Abolishes interaction with PRKAR2A and leads to constitutive activation of RHOA; when associated with P-1260.
Abolishes interaction with PRKAR2Aand leads to constitutive activation of RHOA; when associated with P-1251.
Abolishes interaction with YWHAB, leading to constitutive activation of RHOA and MAPK14.
Decreases guanyl nucleotide exchange activity toward RHOA.
Loss of guanyl nucleotide exchange activity toward RHOA.
Reduces guanyl nucleotide exchange activity toward RHOA.
HLA class II histocompatibility antigen, DO alpha chain
In NS12; also found as somatic mutation in ovarian cancer; increased MAPK signaling; results in craniofacial patterning defects when expressed in zebrafish.
In NS12; associated in cis with C-75; increased MAPK signaling; results in craniofacial patterning defects when expressed in zebrafish; results in craniofacial patterning defects in zebrafish when associated with C-75.
In NS12; decreased GAP-stimulated GTPase activity leading to an accumulation of RRAS2 in its GTP-bound active state; increased MAPK signaling; loss of interaction with RASSF5.
In NS12; increased MAPK signaling; results in craniofacial patterning defects when expressed in zebrafish.
Likely benign variant; associated in cis with H-72 in a patient with Noonan syndrome; has no effect on MAPK signaling; has no effect on craniofacial patterning when expressed in zebrafish; results in craniofacial patterning defects in zebrafish when associated with H-72.
Strongly decreased lysine fatty-acylation.
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.
Found in patients with melanomas; decreased protein phosphatase activity, leading to increased phosphorylation of STING1.
Serine/threonine-protein phosphatase 6 catalytic subunit
Serine/threonine-protein phosphatase 6 catalytic subunit, N-terminally processed
Pleckstrin homology domain-containing family G member 1
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase C
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
Abolishes the ITAM-mediated-activating activity.
Abolished interaction with ATG8 proteins MAP1LC3A, MAP1LC3B and MAP1LC3C.
Abrogates interaction with BAX, resulting in a nonapoptotic protein.
Does not affect interaction with ATG8 proteins MAP1LC3A, MAP1LC3B and MAP1LC3C.
Loss of RASSF1-binding; interacts with BAX in the absence of RASSF1.
No effect on RASSF1-binding; interacts with BAX in the absence of RASSF1.
Weakened interaction with BAX, resulting in a nonapoptotic protein.
HIG1 domain family member 2A, mitochondrial
Trinucleotide repeat-containing gene 18 protein
In HHC3; there is a rightward shift in Ca(2+)concentration-response curves with the mutant compared to wild-type, indicating a decrease in the sensitivity of cells expressing CASR to extracellular calcium.
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.
Decreased interaction with GABARAP and GABARAPL2.
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 7
Loss of interaction with CUL3. Loss of function in TIAM1 degradation.
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.
Androgen-dependent TFPI-regulating protein
Found in an individual with features of Cowden syndrome; unknown pathological significance; associated with increased manganese superoxide dismutase expression; associated with normal reactive oxygen species; associated with no change in AKT expression but a 1.2-fold increase of MAPK expression.
In MC2DN3; results in highly reduced protein expression; results in impaired cellular respiration.
In MC2DN3; results in impaired mitochondrial complex II assembly; results in impaired cellular respiration.
May increase susceptibility for developing paraganglioma, breast and thyroid carcinoma; may be involved in somatic Merkel cell carcinoma; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with a 2.0-fold increase in AKT expression and a 1.7-fold increase in MAPK expression.
May increase susceptibility for developing pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; associated with increased manganese superoxide dismutase expression; associated with increased reactive oxygen species; associated with 1.9-fold increase in both AKT and MAPK expression.
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
Ankyrin repeat and KH domain-containing protein 1
ATP synthase subunit e, mitochondrial, N-terminally processed
Associated with schizophrenia in some populations; results in reduced localization to the nucleus; decreased interaction with chromatin.
Probable disease-associated variant found in a patient with non-specific intellectual disability syndrome.
Probable global transcription activator SNF2L2
Diphosphorylated at Ser-21 and Ser-23, also called form S2.
Monophosphorylated at Ser-23, also called form S1.
Serine/threonine-protein phosphatase with EF-hands 2
Disrupts association with coatomer; when associated with A-194-195-A.
Disrupts association with coatomer; when associated with S-198-199-S.
No inhibition of coatomer-dependent GTP hydrolysis.
Reduced surface and total expression of CASR.
Required for TMED10 and TMED2 cis-Golgi network localization
Transmembrane emp24 domain-containing protein 2
Loss of kinase activity. Loss of binding to TSACC.
Loss of kinase activity. No effect of binding to TSACC.
Testis-specific serine/threonine-protein kinase 6
Endonuclease domain-containing 1 protein
Ras association domain-containing protein 6
Afadin- and alpha-actinin-binding protein
S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1B
Leucine-rich repeat-containing protein 63
Associated with an increased risk for intervertebral disk disease.
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
Breakpoint for translocation to form KAT6B-CREBBP
Serine-rich and transmembrane domain-containing protein 1
Electrogenic aspartate/glutamate antiporter SLC25A13, mitochondrial
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.
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.
Required for interaction with NMDA receptors
Membrane-spanning 4-domains subfamily A member 14
Ankyrin repeat domain-containing protein 18A
Interleukin-1 receptor antagonist protein
Intercalates between bases and promotes DNA bending
Almost abolishes RAN-binding. Does not disrupt binding to AURKB or CDCA8. Disrupts mitotic spindle assembly. Does not disrupt nuclear export.
Baculoviral IAP repeat-containing protein 5
Disrupts interaction with histone H3pT3, no effect on interaction with INCENP.
Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-62 and R-78.
Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-62 and R-79.
Increases ubiquitination and blocks dissociation from centromeres; when associated with R-23; R-78 and R-79.
Increases ubiquitination and blocks dissociation from centromeres; when associated with R-62; R-78 and R-79.
Localizes normally during mitosis but cannot support cell proliferation. Increased affinity for CDCA8/borealin.
Loss of FBXL7 mediated polyubiquitination.
Loss of acetylation. Localization primarily within the cytoplasm.
Loss of acetylation; localization primarily within the cytoplasm; increased likelihood of existing as monomer; stronger binding to XPO1/CRM1.
Mimics acetylation. Localization primarily within the nucleus.
Mimics phosphorylation. Disrupts subcellular localization during mitosis and prevents interaction with INCENP.
No change. Loss of interaction with AURKB; when associated with A-70.
No change. Loss of interaction with AURKB; when associated with A-71.
Prevents phosphorylation by AURKB. Still able to localize correctly but prevents interaction with INCENP.
Abolishes detoxification activity 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 activity on methylglyocal-adducted CoA.
In PARK7; loss of protection against metal cytotoxicity; decreased detoxification activity on methylglyocal-adducted CoA.
In PARK7; no apparent effect on protein stability; impaired mitochondrial morphology; no effect on detoxification activity 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 activity 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 activity 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 activity 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 activity on methylglyocal-adducted CoA.
Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide.
Unknown pathological significance; no effect on detoxification activity on methylglyocal-adducted CoA.
Abolishes the effect on degradation of mitochondrion-associated cytosolic rRNAs.
In LCWM; the loss of a disulfide bond may affect protein folding and stability; the protein is retained in the endoplasmic reticulum and the mitochondria while lysosomal localization is disrupted.
WAS/WASL-interacting protein family member 2
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 hydrolysis of the covalent intermediate between substrate and the catalytic cysteine residue.
Impairs protein folding. Decreases affinity for UDP-glucose. No effect on inhibition by UDP-xylose. No effect on hysteresis and cooperativity.
Important for formation of active hexamer structure
In DEE84; decreased function in glycosaminoglycan biosynthetic process in patient cells; severely decreased protein stability; decreased hexamer formation; severe decrease of UDP-glucose 6-dehydrogenase activity.
In DEE84; severely decreased protein stability; decreased hexamer formation; severe decrease of UDP-glucose 6-dehydrogenase activity.
In DEE84; unknown pathological significance.
In DEE84; unknown pathological significance; may affect splicing.
Loss of hexamer formation. Causes formation of stable dimers. Strongly decreased specific activity at pH 8.4.
Loss of hexamer formation. Causes formation of stable dimers. Strongly reduced affinity for NAD and UDP-glucose, and strongly decreased catalytic efficiency at pH 8.6.
Nearly abolishes enzyme activity. Stabilizes the enzyme in a low-activity hexameric conformation.
No effect on the intrinsically disordered nature of the C-terminus. No effect on affinity for the inhibitor UDP-xylose.
No significant effect on catalytic activity and on affinity for NAD and UDP-glucose. Decreases affinity for the inhibitor UDP-xylose. Disrupts hysteresis and cooperativity.
Reduced affinity for UDP-glucose, and reduced catalytic efficiency.
Stabilizes the active conformation of the hexamer. Decreases affinity for UDP-xylose, but not for UDP-glucose. Disrupts hysteresis and cooperativity.
Strongly decreases affinity for the inhibitor UDP-xylose.
Rho guanine nucleotide exchange factor 38
ATP-dependent 6-phosphofructokinase, platelet type
In JABELS; unknown pathological significance.
Stress-associated endoplasmic reticulum protein 1
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.
Ubiquitin carboxyl-terminal hydrolase 49
Reduces guanine exchange factor activity by over 90%.
In FECD1; unknown pathological significance.
Complement C1q tumor necrosis factor-related protein 5
Abolishes ubiquitination of ERGIC3 and CFTR, and degradation of CFTR; when associated with S-64. Reduces ubiquitination of DLG1; when associated with S-64, S-106 and S-109. Reduces inhibition of HIV-1 virus production and VSVG protein expression; when associated with S-64. Abolishes ubiquitination of IKBKG/NEMO; when associated with S-64 and Q-90.
Abolishes ubiquitination of ERGIC3 and CFTR, and degradation of CFTR; when associated with S-67. Reduces ubiquitination of DLG1 ; when associated with S-67, S-106 and S-109. Reduces inhibition of HIV-1 virus production and VSVG protein expression; when associated with S-67. Abolishes ubiquitination of IKBKG/NEMO; when associated with S-67 and Q-90.
Abolishes ubiquitination of IKBKG/NEMO; when associated with S-64 and S-67.
Abolishes ubiquitination of and interaction with DLG1; when associated with A-97.
Reduces ubiquitination of DLG1. No effect on interaction with DLG1. Abolishes ubiquitination of and interaction with DLG1; when associated with 243-E--V-246 DEL.
Reduces ubiquitination of DLG1; when associated with S-64, S-67 and S-106.
Reduces ubiquitination of DLG1; when associated with S-64, S-67 and S-109.
Required for inhibition of HIV-1 virus production and VSV G protein expression
Binds Mu-conotoxin KIIIA; via amide nitrogen
Binds Mu-conotoxin KIIIA; via carbonyl oxygen
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 autism; 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.
Pro-neuregulin-2, membrane-bound isoform
In HYPT15; loss of expression in homozygous patient cells.
In HYPT15; reduced expression in homozygous patient cells; does not localize to the cell membrane; decreased interaction with LIPH; results in strongly decreased LIPH-mediated synthesis of 2-acyl lysophosphatidic acid.
Abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2. Abolishes transcriptional activation of KDM5C.
In ACCAG; abolishes transcriptional activation of KDM5C; abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2.
In DEE1 and PRTS; also found in non-specific intellectual disability families; frequent variant.
In DEE1; corpus callosum hypoplasia and simplified gyral pattern observed in one patient; reduces sequence-specific DNA-binding; slightly reduces transcriptional repression of LMO1.
In LISX2; abolishes transcriptional activation of KDM5C; abolishes sequence-specific DNA-binding; reduces transcriptional repression of LMO1 and SHOX2.
Loss of homodimerization, activation, and autophosphorylation.
Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-326.
Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-349.
Serine/threonine-protein kinase 4 18kDa subunit
Serine/threonine-protein kinase 4 37kDa subunit
N-alpha-acetyltransferase 16, NatA auxiliary subunit
Abolishes ubiquitin binding; loss of inhibitory activity on NF-kappa-B activation.
ADP-ribosylation factor-like protein 6-interacting protein 6
Leucine-rich repeat and transmembrane domain-containing protein 1
Centrosomal protein of 170 kDa protein B
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.
Huntingtin-interacting protein 1 clathrin-binding
Huntingtin-interacting protein 1-related protein
Cancer/testis antigen family 45 member A10
Cancer/testis antigen family 45 member A5
In PEBAS; unknown pathological significance.
Trafficking protein particle complex subunit 12
Eukaryotic translation initiation factor 2-alpha kinase 3
In AD4; increased mitochondrion-endoplasmic reticulum membrane tethering resulting in increased calcium transfer to mitochondria.
In AD4; results in altered amyloid-beta production and increased amyloid-beta 42/amyloid-beta 40 ratio; loss of function as calcium-leak channel; results in calcium overload in the endoplasmic reticulum; increased mitochondrion-endoplasmic reticulum membrane tethering resulting in increased calcium transfer to mitochondria.
In AD4; unknown pathological significance.
In CMD1V and AD4; unknown pathological significance.
Reduces production of amyloid-beta in APP processing and of NICD in NOTCH1 processing. Increased mitochondrion-endoplasmic reticulum membrane tethering resulting in increased calcium transfer to mitochondria.
Reduces production of amyloid-beta in APP processing.
Dendritic cell-specific transmembrane protein
Exocyst complex component Sec8 N-terminal
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 interaction with MAP1LC3B. No effect on interaction with PHB. No effect on mitochondrial location. Abolishes rescue of Parkin-mediated mitophagy.
Necessary for transcriptional repression
No effect on homodimerization or interaction with PHB. Decreases mitochondrial dynamics. Disrupts mitochondrial-mediated antiviral innate immune response.
Reduces helicity. Decreases homodimerization and interaction with PHB. Disrupts mitochondrial dynamics. Disrupts mitochondrial-mediated antiviral innate immune response.
Breakpoint for translocation to form TRIP11-PDGFRB
Breakpoint for translocation to form the CEP85L-PDGFRB fusion protein
In IBGC4; decreased protein abundance; no effect on receptor activity; decreased PDGF signaling pathway.
In IBGC4; no effect on protein abundance; loss of PDGF beta receptor activity.
In IBGC4; no effect on protein abundance; no effect on receptor activity; decreased PDGF signaling pathway.
In PENTT; gain of function in protein tyrosine kinase activity; shows ligand-independent constitutive signaling.
Loss of interaction with GRB10. Abolishes interaction with RASA1. No effect on phosphatidylinositol 3-kinase activity.
Loss of kinase activity. Abolishes interaction with RASA1. No effect on phosphatidylinositol 3-kinase activity.
Loss of kinase activity; when associated with F-579. No effect on interaction with GRB10.
Loss of kinase activity; when associated with F-581. Strongly reduces interaction with SRC family kinases. No effect on interaction with GRB10.
No effect neither on interaction with GRB10 and RASA1 nor on phosphatidylinositol 3-kinase activity.
No effect on interaction with GRB10. Abolishes interaction with PLCG1; when associated with F-1021.
No effect on interaction with RASA1 and on phosphatidylinositol 3-kinase activity.
Platelet-derived growth factor receptor beta
Reduces kinase activity. No effect on interaction with GRB10. Abolishes interaction with RASA1. No effect on phosphatidylinositol 3-kinase activity.
Strongly reduces up-regulation of cell proliferation. Abolishes interaction with PLCG1; when associated with F-1009. No effect on interaction with GRB10.
Strongly reduces up-regulation of cell proliferation; when associated with F-740. Abolishes phosphatidylinositol 3-kinase activity and interaction with NCK1, and slightly reduces interaction with RASA1. No effect on interaction with GRB10.
Strongly reduces up-regulation of cell proliferation; when associated with F-751. Strongly decreases phosphatidylinositol 3-kinase activity. No effect on interaction with GRB10 and RASA1.
Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-466.
Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-459 and E-470.
Abolishes dimerization and decreases kinase activity but no effect on phosphorylation; when associated with E-466 and E-470.
Abolishes phosphorylation and kinase activity.
Abrogates both 'Lys-48'-linked and 'Lys-33'-linked ubiquitination.
Decreases kinase activity. No effect on phosphorylation.
Decreases kinase activity. Reduced phosphorylation of STING1.
Decreases phosphorylation and kinase activity.
Decreases phosphorylation and kinase activity. Abolishes dimerization.
Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with A-357 or R-448.
Decreases phosphorylation and kinase activity. Abolishes dimerization; when associated with R-355.
Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-30.
Decreases ubiquitination. Abolishes ubiquitination, phosphorylation and kinase activity; when associated with R-401.
In FTDALS4; loss of kinase activity; impairs binding to OPTN.
In FTDALS4; unknown pathological significance.
In IIAE8; loss of kinase activity; loss of autophosphorylation at S-172; loss of IFNB induction.
In IIAE8; unknown pathological significance.
Loss of kinase activity. No effect on dimerization. Loss of USP38-mediated degradation.
Phosphoserine; by autocatalysis and IKKB
Strongly decreases interaction with AZI2, TANK and TBKBP1. No effect on phosphorylation.
Strongly decreases interaction with TANK and TBKBP1. No effect on phosphorylation.
Mas-related G-protein coupled receptor member D
Coiled-coil domain-containing protein 190
Gamma-aminobutyric acid receptor subunit theta
Abolished farnesylation and recruitment to the pathogen-containing vacuoles or vacuole-escaped bacteria. Impaired ability to promote pyroptosis in response to T.gondii infection.
Abolished localization to pathogen-containing vacuoles.
Constitutively dimeric. Localizes at vesicle-like structures at the plasma membrane.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-210, R-382, R-562, R-567 and R-573.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-210, R-382, R-562, R-567 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-210, R-382, R-562, R-573 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-210, R-382, R-567, R-573 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-210, R-562, R-567, R-573 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-209, R-382, R-562, R-567, R-573 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-207, R-210, R-382, R-562, R-567, R-573 and R-587.
In 8KR mutant; abolished ubiquitination by S. flexneri IpaH9.8 when associated with R-209, R-210, R-382, R-562, R-567, R-573 and R-587.
Loss of GTPase activity. Constitutively monomeric. Expressed throughout the cytoplasm, loss of vesicular accumulation. Impaired ability to promote pyroptosis in response to T.gondii infection.
Complex I assembly factor ACAD9, mitochondrial
In MC1DN20; unknown pathological significance.
Loss of long-chain-acyl-CoA dehydrogenase activity. Does not affect mitochondrial complex I assembly.
Inhibits binding to the 9-1-1 complex. Does not inhibit interaction with TOPBP1. Inhibits localizion to sites of DNA damage.
RAD9, HUS1, RAD1-interacting nuclear orphan protein 1
In DEE35; unknown pathological significance.
In ITPAD; complete loss of enzymatic activity at homozygosity; partial loss of activity without ITP accumulation in heterozygous individuals.
Coiled-coil domain-containing protein 71L
Abolishes autophosphorylation. Abolishes interaction with SRC and activation of BMX. Reduces phosphorylation of NEDD9.
In BAIPRCK; loss-of-function variant affecting ion transmembrane transport in response to acetylcholine; does not localize to plasma membrane.
Neuronal acetylcholine receptor subunit alpha-3
In NEDMCMS; increased homodimerization; even in absence of oxidative stress.
In NEDMCMS; may affect splicing; decreased protein abundance; homozygous patient cells show decreased mitochondrial respiratory reserve capacity and compensatory increased glycolytic activity.
In NEDMCMS; unknown pathological significance.
Increased homodimerization even in absence of oxidative stress.
Thioredoxin-related transmembrane protein 2
Eukaryotic translation initiation factor 3 subunit F
50% reduction in interaction with GRB2. No effect on interaction with SHC1.
Fails to bind SHC1. Reduced recruitment of SHC1 to focal adhesions. Slightly reduces interaction with GRB2. Does not affect interaction with RASAL2. Does not affect association with integrin ITGB1.
Impairs interaction with tensin TNS3 and association with integrin ITGB1. 50% reduction in interaction with GRB2. No effect on interaction with unphosphorylated SHC1 but reduces interaction with tyrosine-phosphorylated SHC1. Reduces focal adhesion localization. Reduces cell migration.
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.
Sorting and assembly machinery component 50 homolog
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.
Intramolecular interaction with C-terminus
Intramolecular interaction with N-terminus
Membrane association; releases autoinhibition.
Coiled-coil domain-containing protein 9B
Loss of interaction with ECT2, PARD6A and with SQSTM1.
No effect on the SRC-mediated phosphorylation state. No effect on SRC-induced enzyme activity. Little effect on TRAF6-mediated activation of NF-kappa-B. Decreased binding to KPNB1/importin-beta.
No effect on the SRC-mediated phosphorylation state. No effect on SRC-induced enzyme activity. No effect on TRAF6-mediated activation of NF-kappa-B.
No effect on the SRC-mediated phosphorylation state. Significant reduction of SRC-induced enzyme activity. Greatly reduced TRAF6-mediated activation of NF-kappa-B. Reduces NGF-dependent cell survival.
Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-85.
Slight decrease of interaction with PARD6A. Loss of interaction with PARD6A; when associated with A-91.
In CMH4; also found in a patient with RCM; decreases protein abundance; increases polyubiquitination level; accelerates the degradation process; no effect on phosphorylation; decreases endopeptidase activity; increases apoptotic process.
In CMH4; destabilizes the structure of Ig-like C2-type domain 5.
In CMH4; no effect on protein abundance; no effect on endopeptidase activity.
In CMH4; unknown pathological significance.
In CMH4; unknown pathological significance; as well folded and stable as the wild-type.
May act as a phenotype modifier in cardiomyopathy patients.
Abolishes the SUMO-specific isopeptidase activity.
Altered SUMO-binding and SUMO-specific isopeptidase activity.
Loss of SUMO-binding and catalytic activity.
Solute carrier organic anion transporter family member 1A2
In an ovarian papillary serous adenocarcinoma sample; somatic mutation.
In a lung squamous cell carcinoma sample; somatic mutation.
Myosin light chain kinase family member 4
Abolishes formation of gap junctions. No significant effect on formation of functional hemichannels.
In CTRCT14; autosomal dominant congenital/infantile 'ant-egg' cataract.
In CTRCT14; central nuclear cataract with punctate opacities.
In CTRCT14; nearly abolishes formation of gap junctions; no significant effect on formation of functional hemichannels.
In CTRCT14; nearly abolishes formation of gap junctions; no significant effect on formation of functional hemichannels; not fully penetrant mutation.
In CTRCT14; nuclear progressive cataract.
In CTRCT14; nuclear pulverulent and posterior polar cataract; the mutant affects the formation of gap junction plaques; affects hemichannel permeability.
In CTRCT14; nuclear pulverulent cataract.
In CTRCT14; unknown pathological significance.
Abolishes membrane anchoring via glycosylphosphatidylinositol.
Has no effect on membrane anchoring via glycosylphosphatidylinositol.
Low affinity immunoglobulin gamma Fc region receptor III-B
Kelch repeat and BTB domain-containing protein 3
Electron transfer flavoprotein regulatory factor 1
Abolishes ATPAse activity, no effect on pericentromeric heterochromatin localization.
Impairs interaction with histone H3 peptides and reduces localization to pericentromeric heterochromatin foci.
Impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3) and reduces localization to pericentromeric heterochromatin foci.
Impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3).
Impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3); loss of heterochromatic localization.
Impairs interaction with histone H3 peptides unmethylated at 'Lys-5' (H3K4me0); reduces pericentromeric localization.
In ATRX; atypical; patients presents spastic paraplegia at birth.
In ATRX; greatly impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3) and reduces localization to pericentromeric heterochromatin foci.
In ATRX; impairs interaction with histone H3 peptides and reduces localization to pericentromeric heterochromatin foci.
In ATRX; impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3) and reduces localization to pericentromeric heterochromatin foci.
In ATRX; impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3).
In ATRX; impairs interaction with histone H3 peptides trimethylated at 'Lys-10' (H3K9me3); loss of heterochromatic localization.
In ATRX; unknown pathological significance.
In MRXHF1 and ATRX; originally reported as Juberg-Marsidi syndrome.
In MRXHF1; originally reported as Carpenter-Waziri syndrome.
Found in individuals with delayed sleep phase syndrome; has higher frequency in affected individuals than in healthy controls; unknown pathological significance.
Important for the catalytic mechanism; involved in substrate deprotonation
Does not interact with RAB8A. Does not localize to cilia.
In OCRL; uncertain pathological significance.
In OCRL; uncertain pathological significance; abolishes FAM109A-, FAM109B- and APPL1-binding.
Inositol polyphosphate 5-phosphatase OCRL
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.
Suppression of tumorigenicity 18 protein
In APRTD; Japanese type; allele APRT*J; most common mutation.
Abolished interaction with RNF14 and decreased interaction with EIF2AK4/GCN2.
In ANXD3; unknown pathological significance.
Nucleolus and neural progenitor protein-like N-terminal
In NEDHND; decreased protein abundance in patient cells homozygous for the mutation.
Probable E3 ubiquitin-protein ligase HERC4
Nuclear cap-binding protein subunit 2-like
Calcium/calmodulin-dependent protein kinase type II subunit alpha
In MRD53; decreased protein abundance; increased autophosphorylation; decreased neuronal migration.
In MRD53; increased basal autophosphorylation.
In MRD53; increased ubiquitin-mediated proteasomal degradation with a dominant negative effect on wild-type protein; decreased localization to dendritic spines; no effect on holoenzyme assembly; loss of interaction with SHANK3; loss of interaction with GRIN2B; loss of interaction with CACNB2; loss of interaction with LRRC7; loss of interaction with GRM5; decreased protein serine/threonine kinase activity with a dominant negative effect on wild-type protein; decreased autophosphorylation; changed dendritic spine development; decreased neuronal migration.
In MRD53; no effect on protein abundance; decreased autophosphorylation; decreased neuronal migration.
In MRD53; no effect on protein abundance; increased autophosphorylation; decreased neuronal migration.
In MRD53; no effect on protein abundance; loss of autophosphorylation; loss of neuronal migration.
In MRD53; unknown pathological significance.
In MRD53; unknown pathological significance; no effect on protein abundance; no effect on autophosphorylation; no effect on neuronal migration.
No effect on neuronal migration; when associated with R-42.
No effect on protein stability or degradation. No effect on neuronal migration; when associated with P-286.
Loss of function in inducing TLR2 degradation.
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
Chondroitin sulfate glucuronyltransferase
Interleukin-1 receptor accessory protein-like 1
Structure-specific endonuclease subunit SLX1
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.
Found in two patients with a diagnosis of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome; unknown pathological significance.
Heme-copper oxidase subunit III family profile
In LHON; possible rare primary mutation.
In LHON; secondary mutation; does not seem to directly cause the disease.
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.
Chromodomain-helicase-DNA-binding protein 5
In PMNDS; unknown pathological significance.
Reduced affinity for trimethylated histone H3K27me3.
WAP four-disulfide core domain protein 5
16% reduction in catalytic efficiency toward trimethylamine and 40% increase toward benzydamine and methyl p-tolyl sulfide.
2-fold decrease in affinity for trimethylamine; 3-fold decrease in catalytic efficiency toward methimazole; 3-fold increase in catalytic efficiency toward sulindac; 30% increase in catalytic efficiency toward ethylenethiourea.
35%, 45% and 71% increase in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide, respectively.
65% increase in catalytic efficiency toward trimethylamine and 60% reduction toward benzydamine and methyl p-tolyl sulfide.
In TMAU; 90% reduction in catalytic efficiency toward trimethylamine and benzydamine; 34% reduction in catalytic efficiency toward methyl p-tolyl sulfide; nearly no effect on affinity for these substrates.
In TMAU; loss of activity; affects FAD binding.
In TMAU; more than 90% reduction in catalytic efficiency toward trimethylamine, benzydamine and methyl p-tolyl sulfide.
In TMAU; profoundly alters enzyme function.
Modest increase in catalytic efficiency toward trimethylamine, methimazole, ethylenethiourea and sulindac.
Calmodulin-regulated spectrin-associated protein 1
Sufficient for interaction with calmodulin
Does not affect Ca(2+) affinity as measured by isothermal titration calorimetry of the mutant protein.
N-end rule aminoacyl transferase C-terminal
Calcium-activated chloride channel regulator 1
Dexamethasone-induced Ras-related protein 1
Induces a rapid dissociation of D-glucose.
Abolishes binding to amyloid-beta peptide.
Collagen-like Alzheimer amyloid plaque component
In CFEOM5; causes loss of stability; causes incorrect folding.
Reduces binding to amyloid-beta peptide.
Abolished inhibition by sphingosine-1-phosphate; when associated with A-230.
Abolished inhibition by sphingosine-1-phosphate; when associated with A-325.
Strongly decreased phosphorylation leading to reduced ceramide synthase activity.
G-protein coupled receptors family 2 profile 2
In VBU; affects the regulation of mast cells degranulation; results in increased vibration-induced mast cells degranulation; no effect on localization to plasma membrane.
Strongly reduced affinity for peptide substrate.
Abolishes localization to endosomes and association with PI3P.
Zinc finger FYVE domain-containing protein 16
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.
Loss of interaction with the RPA complex and loss of recruitment to sites of DNA damage.
Disrupts topology with the N-terminus in the lumen instead of the cytoplasm. Abolishes lipid droplet localization and lipid droplet clustering.
Does not affect lipid droplet localization.
Lipid droplet-regulating VLDL assembly factor AUP1
Reduced interaction with ER quality control machinery and misfolded substrates; when associated with 306-K--A-308.
Reduced interaction with ER quality control machinery and misfolded substrates; when associated with 333-L-L-334 Del.
Reduced lipid droplet clustering; when associated with 319-V-E-320 and 333-E-D-334.
Reduced lipid droplet clustering; when associated with R-316 and 319-V-E-320.
Reduced lipid droplet clustering; when associated with R-316 and 333-E-D-334.
Significantly reduced interaction with UBE2G2.
Cytochrome b-c1 complex subunit Rieske, mitochondrial
In MC3DN10; decreased protein abundance.
In MC3DN10; loss of localization to mitochondrial inner membrane; the mutant protein is distributed over the entire cytosol and in the nucleus.
In MDDGA1 and MDDGB1; likely benign variant.
In MDDGA1; associated with the loss of function of alpha dystroglycan as a matrix receptor.
In MDDGA1; severe Walker-Warburg syndrome.
Found as a heterozygous variant in a patient with non-syndromic hearing impairment; unknown pathological significance.
Abolishes 'Lys-63'-linked polyubiquitination.
Important for interaction with BIRC2 and BIRC3
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.
(Microbial infection) N6-acetyllysine; by EIS
Cerebral cavernous malformations 2 protein
Abolished ability to mediate pyroptosis.
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.
Abolished ubiquitination by S.flexneri IpaH7.8.
Decreased ability to trigger pyroptosis.
Decreased ability to trigger pyroptosis. Abolished ubiquitination by S.flexneri IpaH7.8.
Decreased interaction with S.flexneri IpaH7.8.
Decreased interaction with S.flexneri IpaH7.8. Abolished ubiquitination by S.flexneri IpaH7.8; when associated with A-124.
Decreased interaction with S.flexneri IpaH7.8. Abolished ubiquitination by S.flexneri IpaH7.8; when associated with A-208.
Decreased interaction with S.flexneri IpaH7.8. Does not affect ability to trigger pyroptosis.
Does not abolish ubiquitination by S.flexneri IpaH7.8; when associated with R-166.
Does not abolish ubiquitination by S.flexneri IpaH7.8; when associated with R-308.
Does not prevent cleavage by granzyme A (GZMA). Reduced ability to trigger pyroptosis.
Does not relieve autoinhibition. Relieves autoinhibition; when associated with 339-A--A-343.
Does not relieve autoinhibition. Relieves autoinhibition; when associated with D-399.
Reduced ability to trigger pyroptosis; when associated with A-26.
Reduced ability to trigger pyroptosis; when associated with A-51.
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.
Required for interaction with SSNA1 and microtubules
Required for interaction with microtubules
Required for interaction with microtubules and microtubule severing
Eukaryotic translation initiation factor 4H
No association with GAP; when associated with F-362.
No association with NCK. No association with GAP; when associated with F-398.
In MSD; almost abolished enzyme activity.
In MSD; decreases its specific enzyme activity to less than 3%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is almost comparable to wild-type.
In MSD; loss of activity; decreases its specific enzyme activity to about 23%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is decreased.
In MSD; loss of activity; decreases its specific enzyme activity to less than 1%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is almost comparable to wild-type.
In MSD; loss of activity; decreases its specific enzyme activity to less than 1%; does not affect localization of the protein in the endoplasmic reticulum of MSD fibroblasts; protein stability is severely decreased.
In MSD; mild phenotype; reduced but not abolished activity.
In MSD; reduced but not abolished activity.
Low-density lipoprotein receptor-related protein 1B
Abolishes ATPase activity; inhibition of MYC- and CTNNB1-mediated transformation.
Reduces ATPase activity. Decreases interaction with NOPCHAP1. No effect on formation of RUVBL1-RUVBL2 heteromeric complex.
Required for localization to SC35 splicing speckles
Essential to induce neural progenitor proliferation
Abolishes arginine transport. No effect on subcellular location and interaction with Ragulator complex.
Abolishes association with the Ragulator complex.
Abolishes association with the Ragulator complex. Abolishes the interaction with the Rag GTPases heterodimer complex.
Abolishes association with the Ragulator complex. No effect on amino acid transport activity. Abolishes the interaction with the Rag GTPases heterodimer complex.
Abolishes cholesterol binding; when associated with I-460. Does not affect disrupted arginine-mediated activation of mTORC1; when associated with I-460. Does not affect lysosomal localization; when associated with I-460. Increases interactions with both Rag GTPase and Ragulator subunits; when associated with I-460. Loss of L-glutamine transport stimulation by cholesterol.
Abolishes interaction with the Ragulator and Rag GTPases complexes.
Decreases cholesterol binding. Abolishes cholesterol binding; when associated with I-449. Does not affect disrupted arginine-mediated activation of mTORC1; when associated with I-449. Does not affect lysosomal localization; when associated with I-449. Increases interactions with both Rag GTPase and Ragulator subunits; when associated with I-449. Loss of L-glutamine transport stimulation by cholesterol.
Does not affect L-glutamine transport activity.
Does not affect association with the Ragulator complex. Abolishes the interaction with the Rag GTPases heterodimer complex.
Does not affect interaction with the Ragulator and Rag GTPases complexes.
Important for arginine binding and amino acid transport
Moderately affects amino acid transport.
Abolishes cleavage by proprotein convertases.
Abolishes interaction with RAC1 and RND1.
Important for interaction with RAC1 and RND1
Loss of cytoskeleton remodeling in response to SEMA4D.
Strongly reduced interaction with SEMA4D.
Elongin BC and Polycomb repressive complex 2-associated protein
Coiled-coil domain-containing protein 112
Impairs ATPase activity of the MCM-2-7 complex and reduces phosphorylation by the CDC7-DBF4 complex; when associated with A-27 and A-139.
Impairs ATPase activity of the MCM-2-7 complex and reduces phosphorylation by the CDC7-DBF4 complex; when associated with A-27 and A-41.
Impairs ATPase activity of the MCM-2-7 complex and reduces phosphorylation by the CDC7-DBF4 complex; when associated with A-41 and A-139.
In DFNA70; increases the apoptotic process; no effect on cell proliferation and cell cycle phase.
Confers cellular localization similar to full-length form
Probable ATP-dependent RNA helicase DDX28
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.
NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial
Enables C-terminal tetrameric self-assembly at pH 8.0; when associated with F-721.
Enables C-terminal tetrameric self-assembly at pH 8.0; when associated with W-717.
Impairs pH-induced C-terminal tetrameric self-assembly.
Impairs pH-induced C-terminal tetrameric self-assembly; when associated with A-679.
Impairs pH-induced C-terminal tetrameric self-assembly; when associated with A-688.
Impairs self-assembly of N-terminal ends.
Impairs self-assembly of N-terminal ends; when associated with E-105.
Impairs self-assembly of N-terminal ends; when associated with E-109.
Mediates head to head self-assembly of N-terminal ends
Required for pH-induced assembly of C-terminal ends into antiparallel tetramers
Coiled-coil domain-containing protein 184
F-box-like/WD repeat-containing protein TBL1XR1
Found in a patient with epilepsy; unknown pathological significance.
In PRPTS; does not affect assembly into the N-Cor repressor complex.
A disintegrin and metalloproteinase with thrombospondin motifs 18
Heparan sulfate glucosamine 3-O-sulfotransferase 5
Killer cell immunoglobulin-like receptor 3DL1
CAP-Gly domain-containing linker protein 2
In APMR1; unknown pathological significance.
Variant found in a clone obtained from a fibroblast cell line; does not form the essential disulfide bond; results in loss of antiviral activity.
Uracil nucleotide/cysteinyl leukotriene receptor
Abolishes phosphatidylinositol phosphate binding. Abolishes endosomal location.
Decreases KALRN-dependent lamellipodium formation; no effect on interaction with KALRN.
Decreases KALRN-dependent lamellipodium formation; no effect on interaction with KALRN; when associated with A-426.
Decreases KALRN-dependent lamellipodium formation; no effect on interaction with KALRN; when associated with A-428.
Impairs binding to the POLO box domains of PLK1, preventing phosphorylation by PLK1 and recruitment of PLK1 to the spindle.
No effect. Abolishes CDK1-mediated phosphorylation, leading to prematurely recruit PLK1 to the spindle during prometaphase and blocking mitotic progression; when associated with A-481.
No effect. Reduces in vitro cyclin E-CDK2 phosphorylation and causes extensive bundling of microtubules to the mitotic spindle; when associated with A-470.
Weakly reduces binding to the POLO box domains of PLK1.
Completely abolishes phosphorylation by ALK3 in vitro. NEDD9 and ASNS activation in response to BMPs is abolished.
Found in patient with Joubert syndrome; unknown pathological significance.
Abolishes binding to T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence.
Abolishes repression of tumor suppressor ARF/p14ARF expression.
In VETD; de novo variant; decreased transcriptional regulatory activity; no effect on localization to the nucleus.
In VETD; unknown pathological significance; decreased transcriptional regulatory activity; no effect on localization to the nucleus.
Severely impairs repression of tumor suppressor ARF/p14ARF expression.
Reduces cell surface expression and response to linolenic acid and synthetic agonists.
Reduces response to linolenic acid. Reduces response to synthetic agonists.
Reduces response to linolenic acid. Strongly reduces response to synthetic agonists.
Strongly reduces response to linolenic acid. Strongly reduces response to synthetic agonists.
Polypeptide N-acetylgalactosaminyltransferase 10
Impaired ability to act as an anti-inflammatory role during the hepatic acute phase response.
Nuclear receptor subfamily 5 group A member 2
Reduced DNA binding. Loss of transactivation.
Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-342.
Reduced phospholipid binding. Strongly reduced transactivation; when associated with W-416.
Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-168 and A-172.
Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-168.
Slightly reduced DNA binding. Strongly reduced transactivation; when associated with A-96 and A-172.
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.
Amyloid-beta A4 precursor protein-binding family A member 1
Abolishes DNA-binding; when associated with G-31 and G-53.
Abolishes DNA-binding; when associated with G-31 and G-82.
Abolishes DNA-binding; when associated with G-53 and G-82.
Abolishes phosphorylation. Markedly diminished pre-mRNA splicing activity; when associated with A-411. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-358; A-385; A-404; A-411; A-417 and A-424.
Abolishes phosphorylation. Markedly diminished pre-mRNA splicing activity; when associated with A-438. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-358; A-385; A-404; A-417; A-424 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-358; A-385; A-404; A-411; A-417 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-358; A-385; A-404; A-411; A-424 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-358; A-385; A-411; A-417; A-424 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-303; A-385; A-404; A-411; A-417; A-424 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-227; A-358; A-385; A-404; A-411; A-417; A-424 and A-438.
Abolishes phosphorylation. No effect on homodimerization nor on nuclear localization; when associated with A-303; A-358; A-385; A-404; A-411; A-417; A-424 and A-438.
In PEAMO; decreased function in the organization of microtubule cytoskeleton and mitotic splindle.
D-2-hydroxyglutarate dehydrogenase, mitochondrial
In D2HGA1; mild phenotype; unknown pathological significance; moderate reduction in catalytic activity.
In D2HGA1; severe phenotype; unknown pathological significance; almost complete loss of catalytic activity.
In D2HGA1; severe phenotype; unknown pathological significance; significant reduction in catalytic activity.
In D2HGA1; unknown pathological significance.
In D2HGA1; unknown pathological significance; almost complete loss of catalytic activity.
In D2HGA1; unknown pathological significance; complete loss of catalytic activity.
In D2HGA1; unknown pathological significance; moderate reduction in catalytic activity.
In D2HGA1; unknown pathological significance; no effect on catalytic activity.
In D2HGA1; unknown pathological significance; significant loss of catalytic activity.
Significantly reduced catalytic activity.
Double C2-like domain-containing protein beta
Negatively regulates targeting to plasma membrane
B box and SPRY domain-containing protein
Ankyrin repeat and SAM domain-containing protein 1A
In POF5; likely benign variant; decreased nuclear location; intranuclear and cytosolic aggregates.
In POF5; unknown pathological significance; decreased nuclear location; intranuclear and cytosolic aggregates.
In POF5; unknown pathological significance; decreased transactivation activity.
In POF5; unknown pathological significance; decreased transactivation activity; decreased nuclear location; intranuclear and cytosolic aggregates.
In POF5; unknown pathological significance; loss of transactivation activity; intranuclear and cytosolic aggregates; not statistically significant decrease of nuclear location.
In POF5; unknown pathological significance; not statistically significant decrease of nuclear location.
No effect on transactivation activity; not statistically significant decrease of nuclear location.
Abolished interaction with STING1, MAVS or TICAM1.
Acts as a constitutively activated IRF3.
Complete loss of viral infection induced phosphorylation.
Decreased IFNB induction upon Sendai virus infection.
Highly diminished ISGylation; when associated with R-193 and R-360.
Highly diminished ISGylation; when associated with R-193 and R-366.
Highly diminished ISGylation; when associated with R-360 and R-366.
In IIAE7; loss of viral infection-induced phosphorylation at S-386; loss of viral infection-induced homodimerization; loss of viral infection-induced transcription factor activity; unable to activate interferon transcription in response to viral infection; decreased IFNB induction upon Sendai virus infection.
No effect on IFNB induction upon Sendai virus infection.
Phosphomimetic mutant; interacts with CREBBP; when associated with E-386.
Phosphomimetic mutant; interacts with CREBBP; when associated with E-396.
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.
26S proteasome non-ATPase regulatory subunit 11
Does not affect phosphorylation by AMPK; when associated with A-14 and A-272.
Does not affect phosphorylation by AMPK; when associated with A-79 and A-272.
Does not affect phosphorylation by AMPK; when associated with A14- and A-79.
A-kinase anchor protein 7 RI-RII subunit-binding
A-kinase anchor protein 7 isoforms alpha and beta
Abolishes membrane localization and affects its ability to inhibit ENaC activity in a sodium-dependent manner.
Required for apical membrane localization
Choriogonadotropin subunit beta variant 2
In FASPS4; reduced protein stability; mislocalization in cytoplasm; reduced interaction with CRY2; enhanced destabilization of the PER2-CRY2 complex; reduced repressor activity of CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1; does not affect interaction with PER2.
Required for homodimerization and for interaction with CRY1 and CHEK1
Fails to sequester viral nucleoproteins, no antiviral activity.
Interferon-induced GTP-binding protein Mx1
Interferon-induced GTP-binding protein Mx1, N-terminally processed
Loss of GTP-binding. Loss of potentiation of TRPC6 activity. Loss of protection against viral infection.
Loss of GTP-binding. Loss of protection against viral infection.
Loss of GTP-hydrolysis. No effect on GTP-binding, nor on potentiation of TRPC6 activity.
Loss of antiviral activity towards CCHFV and LACV.
N-acetylmethionine; in Interferon-induced GTP-binding protein Mx1; alternate
No effect on GTP-binding, nor on viral infection.
Glutamate receptor ionotropic, kainate 5
2-oxoglutarate and iron-dependent oxygenase domain-containing protein 3
Found in a cutaneous malignant melanoma sample; somatic mutation; induces cell transformation and confers resistance to apoptosis.
In DEDDFA; unknown pathological significance.
In DEDDFA; unknown pathological significance; also found in a colorectal adenocarcinoma sample; somatic mutation.
In DFNA75; unknown pathological significance.
In an ovarian serous carcinoma sample; somatic mutation.
Transformation/transcription domain-associated protein
No mitotic phosphorylation. No binding to spindle apparatus.
Still binds to the mitotic spindle but mitotic progression is impaired.
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A
Alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A soluble form
EF-hand and coiled-coil domain-containing protein 1
Decreased 3',5'-cyclic-AMP phosphodiesterase activity. Loss of Mg2(+)-binding.
In isoform 5, isoform N3 and isoform 12.
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
LysM and putative peptidoglycan-binding domain-containing protein 3
Abrogates induction of filamentous growth in yeast; when associated with A-28 and A-30.
Abrogates induction of filamentous growth in yeast; when associated with A-28 and A-33.
Abrogates induction of filamentous growth in yeast; when associated with A-30 and A-33.
MORC family CW-type zinc finger protein 1
Zinc finger B-box domain-containing protein 1
Abolished binding to DEPTOR, TFE3 and MITF substrates.
Abolished binding to TFE3 and MITF substrates.
Spermatogenesis-associated serine-rich protein 2
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
Found in two patients with Kufor-Rakeb syndrome also carrying R-877 in ATP13A2.
Important for dimerization and interaction with PSMF1
In PARK15; no effect on interaction with PRKN.
In PARK15; unknown pathological significance.
Decreases 16-fold the affinity for PtdIns(3,4,5)P3.
Decreases 8-fold the affinity for PtdIns(3,4,5)P3.
In isoform 2, isoform 3, isoform 4 and isoform 7.
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1
Heterogeneous nuclear ribonucleoprotein U-like protein 2
Cytochrome b-c1 complex subunit 6-like, mitochondrial
Fumarylacetoacetate hydrolase domain-containing protein 2B
Histone-lysine N-methyltransferase, H3 lysine-36 specific
In SOTOS; strongly reduced enzyme activity.
Inhibits enzyme activity in the absence of bound histone
Abolishes catalytic activity; abolishes interaction with PARP14.
Protein mono-ADP-ribosyltransferase PARP10
Abolished 'Lys-63'-linked ubiquitination by RNF167.
About two-fold prolonged half-life in cycloheximide/CHX time course.
C-terminal domain; mediates TORC1 regulation
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.
N-terminal domain; mediates the alkylhydroperoxide reductase activity
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.
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.
Interchain (between heavy and light chains)
Leucine-rich repeat-containing protein 74A
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.
Abolishes cleavage and secretion in apoptotic cells. No effect on kinase activity.
Abolishes nuclear export in response to PMA treatment.
Decreases SPP production in nucleus. Abolishes increase of histone acetylation. No effect on association with histone 3.
Loss of location to cell membrane. Not secreted. No effect on kinase activity.
No effect on cleavage and secretion in apoptotic cells. No effect on kinase activity.
Required for binding to sulfatide and phosphoinositides and for membrane localizatione
Strongly reduces phosphorylation levels.
LPXY motif; mediates binding to WW domain-containing proteins
PPXY motif; mediates binding to WW domain-containing proteins
Significantly impairs interaction with YAP1.
Transmembrane gamma-carboxyglutamic acid protein 2
Membrane-spanning 4-domains subfamily A member 4A
Observed with a marginally higher frequency in patients with systemic lupus erythematosus.
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.
Ribosomal RNA adenine methylase transferase N-terminal
Iroquois-class homeodomain protein IRX-2
Impairs protein solubility. Abolishes catalytic activity.
Mitochondrial enolase superfamily member 1
Found in a patient with CDLS1; unknown pathological significance; no effect on interaction with NIBPL.
Zinc finger MYND domain-containing protein 19
RNA polymerase-associated protein CTR9 homolog
Ankyrin repeat domain-containing protein 42
Binding to the DYNLT2B-DYNLT1/DYNLT3 dimer
Cytoplasmic dynein 2 intermediate chain 1
In SRTD8; Reduces interaction with IFT proteins.
In SRTD8; does not affect interaction with DYNC2I2.
Tissue-resident T-cell transcription regulator protein ZNF683
Meiosis regulator and mRNA stability factor 1
Amiloride-sensitive sodium channel subunit delta
Decreased RNA-binding; when associated with A-143; A-145: A-149 and A-156. Does not rescue diminished mitochondrial transcription induced by EtBr; when associated with A-143; A-145: A-149 and A-156.
Decreased RNA-binding; when associated with A-143; A-145: A-149 and A-158. Does not rescue diminished mitochondrial transcription induced by EtBr; when associated with A-143; A-145: A-149 and A-158.
Decreased RNA-binding; when associated with A-143; A-145: A-156 and A-158. Does not rescue diminished mitochondrial transcription induced by EtBr; when associated with A-143; A-149: A-156 and A-158.
Decreased RNA-binding; when associated with A-143; A-149: A-156 and A-158. Does not rescue diminished mitochondrial transcription induced by EtBr; when associated with A-143; A-149: A-156 and A-158.
Decreased RNA-binding; when associated with A-145; A-149: A-156 and A-158. Does not rescue diminished mitochondrial transcription induced by EtBr; when associated with A-145; A-149: A-156 and A-158.
Mitochondrial transcription rescue factor 1
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 HGPPS2; unknown pathological significance.
In MRMV1; unknown pathological significance.
In allotype C4A1, allotype C4A3a, allotype C4A6.
Isoglutamyl cysteine thioester (Cys-Gln)
Responsible for effective binding to form amide bonds with immune aggregates or protein antigens
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.
In CMYP15; affects regulation of muscle contraction.
Actin-related protein 2/3 complex subunit 2
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.
Necessary for interaction with NR6A1 C-terminus
Necessary for interaction with NR6A1 N-terminus
Not associated with susceptibility to breast cancer.
Slightly impairs the selectivity for 'K-63'-linked ubiquitin.
Strongly reduces ubiquitin binding via UIM 1.
Increased phosphorylation. Increases muscle specific force.
Loss of phosphorylation by AMPK. Decreases muscle specific force.
Solute carrier family 2, facilitated glucose transporter member 6
Found in a patient with Meckel syndrome; 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.
Required for microtubule association, proximal axon localization and axon formation
Required for proximal axon localization, axon formation and migration
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.
Abolishes interaction with histone H3 di- and trimethylated at 'Lys-4'.
Breakpoint for translocation to form the NUP98-KDM5A fusion protein
No effect on interaction with histone H3 di- and trimethylated at 'Lys-4'.
No effect on lysine-specific histone demethylase activity; when associated with S-626.
No effect on lysine-specific histone demethylase activity; when associated with S-636.
Phosphatidic acid phosphatase type 2/haloperoxidase
Acetyl-CoA acetyltransferase, mitochondrial
In 3KTD; decreased acetyl-CoAC-acyltransferase activity; less than 10% of the degradative/thiolase activity.
In 3KTD; decreased protein abundance; decreased acetyl-CoAC-acyltransferase activity; less than 10% of the degradative/thiolase activity.
In 3KTD; decreased protein stability; decreased acetyl-CoAC-acyltransferase activity; less than 10% of the degradative/thiolase activity.
In 3KTD; loss of acetyl-CoAC-acyltransferase activity; no degradative/thiolase activity.
In 3KTD; loss of protein solubility; loss of acetyl-CoAC-acyltransferase activity; no degradative/thiolase activity.
Increases nucleophilicity of active site Cys
Less than 3% of wild-type activity using succinamate as substrate.
Loss of activity using succinamate as substrate.
Found in patients with non-obstructive azoospermia; unknown pathological significance.
Stimulated by retinoic acid gene 8 protein homolog
Participates in a stacking interaction with the adenine ring of AMP
Phosphoserine; by PHK; in form phosphorylase A
AT-rich interactive domain-containing protein 2
Exosome complex component CSL4 C-terminal
LysM and putative peptidoglycan-binding domain-containing protein 1
In ARWH3; disruption of keratin intermediate filament formation formed via heterodimerization with KRT5.
In ARWH3; reduces keratin intermediate filamen formation; impairs cytoskeleton assembly.
FXYD domain-containing ion transport regulator
NF-kappa-B inhibitor-interacting Ras-like protein 2
Abolishes histone H3K36me3-binding and localization at double-strand breaks (DSBs).
In MCDR4; leads to thinning in both the outer nuclear layer and whole retina and to impaired retinal function, when tested in a heterologous system.
Found in a patient diagnosed with multiple sclerosis; unknown pathological significance.
Found in a patient diagnosed with multiple sclerosis; unknown pathological significance; decreased protein abundance; not changed aminopeptidase activity.
In IMD78; decreased protein abundance; decreased aminopeptidase activity.
1-acyl-sn-glycerol-3-phosphate acyltransferase gamma
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.
Impairs interaction with AMBRA1, DTL and DCAF5.
Impairs interaction with AMBRA1, DTL, DET1, DCAF1, DCAF5, DCAF11 and DCAF8.
Impairs interaction with AMBRA1, ERCC8, DCAF5 and DCAF11.
Slightly impairs interaction with CUL4A.
Strongly impairs interaction with CUL4A.
WD repeat beta-propeller B; Interaction with CUL4A
Vacuolar protein sorting-associated protein 52 homolog
ATP synthase subunit C lysine N-methyltransferase
Abolished protein-lysine N-methyltransferase activity and ability to promote chronic pain.
Abolished protein-lysine N-methyltransferase activity.
Abolished ability to rescue stalled ribosomes.
UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 1
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.
In SPGF81; unknown pathological significance; loss of protein expression in vivo in patient's spermatozoa, but no effect in transfected cells.
Processed cysteine-rich motor neuron 1 protein
Required for cellular lifespan extension
In MC1DN6; loss of catalytic activity; no change in Km value for ubiquinone-1.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial
Mediator of RNA polymerase II transcription subunit 9
In SPCH1; reduced interaction with TBR1.
In CMS2A; slow-channel mutation; increases gating equilibrium constant by 33-fold, owing to increased opening rate and decreased closing rate; no effect on the choline dissociation rate constant.
In CMS2C; impairs AChR assembly by disrupting a specific interaction between beta and delta subunits.
Abolishes interactionj with YWHAZ and YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation.
Impairs polyubiquitin binding, abolishes inhibition of IKK activation.
Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-779.
Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-782.
Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614.
Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-615 or R-626.
In AIFBL1; increases inflammatory cytokine secretion; increases NF-kappaB signaling.
Loss of 'Lys-63' deubiquitinating activity. Down-regulation of TNF-induced NF-kappa-B activity less effective.
Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-624.
Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-627.
Minor effect on 'Lys-48' deubiquitinase activity.
Minor effect on 'Lys-48' deubiquitinase activity. Strongly reduced 'Lys-63' deubiquitinase activity.
No effect on ubiquitin ligase activity; when associated with A-521.
No effect on ubiquitin ligase activity; when associated with A-524.
Required for lysosomal localization and for TRAF2 lysosomal degradation
Required for proteasomal degradation of UBE2N and UBE2D3, TRAF6 deubiquitination, and TAX1BP1 interaction with UBE2N
Strongly reduced 'Lys-48' deubiquitinase activity.
Strongly reduced deubiquitinase activity.
Sufficient for inhibitory activity of TNF-induced NF-kappa-B activity
Tumor necrosis factor alpha-induced protein 3
Found in a patient with Beckwith-Wiedemann syndrome and multi-locus imprinting disturbance; unknown pathological significance.
Found in a patient with Silver-Russell syndrome and multi-locus imprinting disturbance; unknown pathological significance.
Found in a patient with features of Silver-Russell syndrome and multi-locus imprinting disturbance; unknown pathological significance.
Found in a patient with mild cognitive retardation and multi-locus imprinting disturbance; unknown pathological significance.
Found in an individual with no overt clinical disease and multi-locus imprinting disturbance; unknown pathological significance.
Found in patients with Beckwith-Wiedemann syndrome and multi-locus imprinting disturbance; when associated in cis with Q-76; unknown pathological significance.
Found in patients with Beckwith-Wiedemann syndrome and multi-locus imprinting disturbance; when associated in cis with T-52; unknown pathological significance.
Found in patients with female infertility; unknown pathological significance.
Found in patients with female infertility; unknown pathological significance; reduces protein abundance in oocytes and embryos.
Found in patients with female infertility; when associated in cis with C-462; unknown pathological significance.
Found in patients with female infertility; when associated in cis with P-143; unknown pathological significance.
NACHT, LRR and PYD domains-containing protein 5
In UHS1; forms large aggregates; decreases protein-arginine deiminase activity.
9 X 9 AA approximate tandem repeat of [AP]-P-G-G-P-Y-G-G-P-P
Decreased ubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex.
Does not affect ubiquitination by the BCR(KLHL12) E3 ubiquitin ligase complex.
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1
Found in patients with North American Indian childhood cirrhosis; unknown pathological significance; does not affect nucleolar protein location; decreased interaction with HIVEP1 measured in yeast two-hybrid screening.
U3 small nucleolar RNA-associated protein 4 homolog
Decreased interaction with WDR45/WIPI4 and ability to promote autophagy.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, E-101, R-167, E-171, R-193, R-200, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, E-171, R-193, R-200, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-193, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-193, R-200, E-223, R-285 and R-304.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-193, R-200, E-223, R-285 and R-328. In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, K-167, R-171, E-193, K-259 and E-285.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-193, R-200, E-223, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-193, R-200, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, E-171, R-200, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, E-101, R-167, R-193, R-200, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-54, R-82, R-167, E-171, R-193, R-200, E-223, R-285, R-304 and R-328.
In Mutant 1; abolished lipid transfer activity; when associated with R-82, E-101, R-167, E-171, R-193, R-200, E-223, R-285, R-304 and R-328.
In Mutant 2; abolished lipid transfer activity; when associated with D-103, K-167, R-171, E-193, K-259, E-285 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, K-167, E-193, K-259, E-285 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, K-167, R-171, E-193, E-285 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, K-167, R-171, E-193, K-259 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, K-167, R-171, K-259, E-285 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80, D-103, R-171, E-193, K-259, E-285 and R-304.
In Mutant 2; abolished lipid transfer activity; when associated with E-80,K-167, R-171, E-193, K-259, E-285 and R-304.
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
Reduces tail-anchored proteins delivery.
Required and sufficient for interaction with BAG6
Strongly inhibits interaction with BAG6.
Found in a patient with epilepsy and neurodevelopmental anomalies; unknown pathological significance; affects channel properties resulting in slower channel deactivation.
Found in a patient with epilepsy but without evidence of neurodevelopmental impairment; unknown pathological significance; affects channel properties resulting in slower channel deactivation.
Found in a patient with neurodevelopmental anomalies; unknown pathological significance.
Potassium voltage-gated channel subfamily A member 6
Leucine-rich repeats and immunoglobulin-like domains protein 1
Detected in a patient with mitochondrial complex I deficiency; uncertain pathological significance.
In LDYT; possible rare primary mutation; decrease in enzyme activity.
In LHON; primary mutation; almost no vision recovery; most frequent mutation; seems to have no effect on electron transfer activity of the complex in inner mitochondrial membrane preparations.
NADH:quinone oxidoreductase/Mrp antiporter membrane subunit
NADH:ubiquinone oxidoreductase chain 4 N-terminal
Abolishes glycosylation; when associated with S-107 and S-152.
Abolishes glycosylation; when associated with S-107 and S-229.
Abolishes glycosylation; when associated with S-152 and S-229.
Cysteine-rich and transmembrane domain-containing protein 1
Helical; Voltage-sensor; Name=S4 of repeat I
Helical; Voltage-sensor; Name=S4 of repeat II
Helical; Voltage-sensor; Name=S4 of repeat III
Helical; Voltage-sensor; Name=S4 of repeat IV
In FEPS3; causes hyperexcitability of dorsal root ganglion neurons; hyperpolarizes channel activation; slows deactivation; depolarizes steady-state fast-inactivation.
In FEPS3; increased voltage-gated sodium channel activity; causes hyperexcitability of dorsal root ganglion neurons; depolarizes resting membrane potential; enhances spontaneous firing; hyperpolarizes channel activation; slows deactivation; decreases rates of current decay; does not change slow-inactivation.
In FEPS3; increased voltage-gated sodium channel activity; slows deactivation; depolarizes resting membrane potential; enhances spontaneous firing; decreases rates of current decay; does not change fast-inactivation; does not change slow-inactivation.
In HSAN7; cold-aggravated peripheral pain seen in some patients; enhances the channel activity by shifting the voltage dependence of channel opening to hyperpolarized potentials thereby giving rise to hyperexcitability of nociceptors; causes hyperexcitability and reduced cold-sensitivity of dorsal root ganglion neurons.
In HSAN7; increased voltage-gated sodium channel activity; results in excessive channel activity at resting voltages; causes sustained depolarization of nociceptors and impaired generation of action potentials; causes aberrant synaptic transmission; causes transient hyperexcitability of dorsal root ganglion neurons.
Sodium channel protein type 11 subunit alpha
Sulfotyrosine; in submandibular gland form
with 1 phosphate group and 1 sulfate group.
with 1 phosphate group and 2 sulfate groups.
with 1 phosphate group and 3 sulfate groups.
with 1 phosphate group and 4 sulfate groups.
Leucine-rich repeat-containing protein 17
Type 2 lactosamine alpha-2,3-sialyltransferase
Decreased binding to RAN. Abolishes binding to RAN; when associated with K-50.
Found in patients with Brugada syndrome; loss of function in enhancing the expression of SCN5A at the cell membrane; unknown pathological significance.
Found in patients with cardiac arrhythmia and in patients with Brugada syndrome; loss of function in enhancing the expression of SCN5A at the cell membrane; unknown pathological significance.
Strongly decreased binding to RAN. Abolishes binding to RAN; when associated with K-53.
Probable ATP-dependent RNA helicase DHX35
No effect on DYNLL1-binding; when associated with G-436.
No effect on DYNLL1-binding; when associated with G-448.
Decreases the recruitment within caveola.
Markedly decreases the recruitment within caveola.
Decreases homodimerization but nearly no effect on kinetic parameters.
Increases homodimerization and turnover number with phenanthridine as substrate; nearly no effect on kinetic parameters with benzaldehyde, phtalazine and chloroquinazolinone as substrate.
Increases homodimerization; abolishes enzymatic activity on phenanthridine; decreases turnover number with benzaldehyde, phtalazine and chloroquinazolinone as substrate, while nearly no effect on the KM.
No effect on dimerization. Loss of oxidase activity.
No effect on dimerization; no effect on oxidase activity.
Proton acceptor; for azaheterocycle hydroxylase activity
Beta-hexosaminidase eukaryotic type N-terminal
Critical for hydrolysis GM2 gangliosides
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.
Protein phosphatase 1 regulatory subunit 26
Required for interaction with SORBS1 (Ten-1 ICD form)
Dehydrogenase/reductase SDR family member 4-like 2
D-beta-hydroxybutyrate dehydrogenase, mitochondrial
Does not affect interaction with ITCH; when associated with A-257. Loss of interaction with ITCH; when associated with A-257; A-276; A-277 and A-278.
Does not affect interaction with ITCH; when associated with A-259. Loss of interaction with ITCH; when associated with A-259; A-276; A-277 and A-278.
Does not affect interaction with ITCH; when associated with A-276 and A-277.Loss of interaction with ITCH; when associated with A-257; A-259; A-276 and A-277.
Does not affect interaction with ITCH; when associated with A-276 and A-278.Loss of interaction with ITCH; when associated with A-257; A-259; A-276 and A-278.
Does not affect interaction with ITCH; when associated with A-277 and A-278. Loss of interaction with ITCH; when associated with A-257; A-259; A-277 and A-278.
Loss of infection by Venezuelan equine encephalitis virus.
Low-density lipoprotein receptor class A domain-containing protein 3
Found in a patient with autism spectrum disorder without history of seizures; unknown pathological significance.
In DEE108; unknown pathological significance.
Microtubule-associated serine/threonine-protein kinase 3
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.
Required for interaction with DNA and JUN and for functional cooperation with JUN
Mediates preference for acidic residues at subsite P1'
N-linked (GlcNAc...) asparagine; atypical
Sia-alpha-2,3-Gal-beta-1,4-GlcNAc-R:alpha 2,8-sialyltransferase
Histone-lysine N-trimethyltransferase SMYD5
Disrupts interaction with CBX5, loss of localization to centromeres in interphase, no effect on localization to centromeres in mitosis; when associated with A-451 and A-453.
Disrupts interaction with CBX5, loss of localization to centromeres in interphase, no effect on localization to centromeres in mitosis; when associated with A-451 and A-455.
Disrupts interaction with CBX5, loss of localization to centromeres in interphase, no effect on localization to centromeres in mitosis; when associated with A-453 and A-455.
In CAID; patient fibroblasts exhibit significantly faster cell proliferation than controls; during mitosis the mutant protein is localized in an ordered fashion around the centromeres but display a rather homogeneous cytoplasmic localization pattern.
Loss of interaction with PPP2CA and PPP2R1A and loss of centromeric localization.
Loss of phosphorylation and presence of misaligned chromosomes; when associated with A-507.
Loss of phosphorylation; and presence of misaligned chromosomes; when associated with A-14.
Loss of proper localization to spindle pole and mitotic spindle. Significant increase in split spindle poles.
Necessary for interaction with PPP2CA and PPP2R1A
Sufficient to mediate interaction with SGIP1
In LVNC1; unknown pathological significance.
In isoform 2, isoform 5, isoform 8, isoform 13, isoform 14, isoform 15 and isoform 16.
In isoform 3, isoform 4, isoform 5, isoform 8, isoform 12 and isoform 16.
In isoform 4, isoform 6, isoform 8, isoform 9, isoform 10, isoform 11, isoform 13, isoform 14, isoform 15, isoform 16 and isoform 17.
In isoform 6, isoform 8, isoform 10 and isoform 11.
Abolishes endonuclease activity on both Hollyday junctions and 5' flap substrates.
Found in a renal cell carcinoma case; somatic mutation.
No effect on endonuclease activity on Hollyday junctions. Slightly reduces endonuclease activity on 5' flap substrates.
No effect on endonuclease activity on both Hollyday junctions and 5' flap substrates.
Reduces by 25% endonuclease activity on Hollyday junctions and by 65% on 5' flap substrates.
Reduces by 50% endonuclease activity on both Hollyday junctions and 5' flap substrates.
Strongly reduces endonuclease activity on both Hollyday junctions and 5' flap substrates.
U3 small nucleolar ribonucleoprotein protein IMP3
In MRT51; loss of protein solubility; increased aggregation in the cytoplasm.
In MRT51; no effect on protein abundance; no effect on protein localization to the cytoplasm; decreased thermal stability; decreased ligand affinity for S-adenosyl-L-methionine; loss of histamine N-methyltransferase activity.
Zinc finger CCHC domain-containing protein 2
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.
Carcinoembryonic antigen-related cell adhesion molecule 4
No internalization of bacteria; when associated with F-222.
No internalization of bacteria; when associated with F-233.
Found as heterozygous variant in patients with Bardet-Biedl syndrome; might have a modifying effect on disease phenotype.
Found in patients with Bardet-Biedl syndrome carrying homozygous mutations in other BBS genes; might have a modifying effect on disease phenotype.
In BBS5; found in patient of Sri Lankan origin; not detected in patients of Northern European origin.
Solute carrier family 2, facilitated glucose transporter member 12
U6 snRNA-associated Sm-like protein LSm1
Probably protective against leprosy when associated with A-399 and F-407.
Trafficking protein particle complex subunit 8
Reduced EGF-induced phosphorylation and decreased association with NHERF1. Loss of EGF-induced phosphorylation and decreased association with NHERF1; when associated with F-959.
Reduced EGF-induced phosphorylation and decreased association with NHERF1. Loss of EGF-induced phosphorylation and decreased association with NHERF1; when associated with F-972.
Short transient receptor potential channel 4
Spermatogenesis-associated protein 6 N-terminal
In NDCAGF; unknown pathological significance.
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.
Mediates interaction with LAT, PTK2/FAK1, JAK1 and JAK3
Found in a patient with severe intellectual disability, seizures, stereotypic behavior, high pain threshold and sleep disturbances.
In KPA; reduced alpha-2 macroglobulin receptor activity; reduced protein abundance.
Loss of tyrosine phosphorylation. Abolishes interaction with SHC1 and GULP1.
Low-density lipoprotein receptor-related protein 1 515 kDa subunit
Low-density lipoprotein receptor-related protein 1 85 kDa subunit
Low-density lipoprotein receptor-related protein 1 intracellular domain
No detectable effect on phosphorylation.
Prolow-density lipoprotein receptor-related protein 1
Recognition site for proteolytical processing
Strongly reduced phosphorylation and loss of interaction with SHC1; when associated with A-4460; A-4517 and A-4520.
Strongly reduced phosphorylation and loss of interaction with SHC1; when associated with A-4460; A-4517 and A-4523.
Strongly reduced phosphorylation and loss of interaction with SHC1; when associated with A-4460; A-4520 and A-4523.
Strongly reduced phosphorylation and loss of interaction with SHC1; when associated with A-4517; A-4520 and A-4523.
Immediate early response gene 5-like protein
Leucine-rich repeat-containing protein 37A
Putative spermatogenesis-associated protein 31C1
In COXPD54; decreased protein levels in homozygous patient cells; impaired mitochondrial RNA processing in homozygous patient cells.
In COXPD54; results in decreased mitochondrial tRNA 5'-end processing as shown by assays with mitochondrial ribonuclease P complex reconstituted in vitro.
In COXPD54; unknown pathological significance.
Mitochondrial ribonuclease P catalytic subunit
DRY motif; important for ligand-induced conformation changes
NPxxY motif; important for ligand-induced conformation changes and signaling
Zinc finger and BTB domain-containing protein 18
Glycerol-3-phosphate dehydrogenase 1-like protein
In BRGDA2; unknown pathological significance; decreased enzymatic activity and significant reduction of sodium current when coexpressed with SCN5A in HEK cells.
In BRGDA2; unknown pathological significance; decreased enzymatic activity; affects SCN5A membrane expression; reduction of sodium current when coexpressed with SCN5A in HEK cells.
In BRGDA2; unknown pathological significance; significant reduction of sodium current when coexpressed with SCN5A in HEK cells.
Does not change subcellular localization; when associated with A-176.
Does not change subcellular localization; when associated with A-178.
Does not change subcellular localization; when associated with A-91.
Does not change subcellular localization; when associated with A-95.
Does not inhibit interaction with ESR1 and ER-coactivation activity.
Does not inhibit interaction with ESR1 and ER-coactivation activity. Localizes mainly in the nucleus; when associated with A-165.
Does not inhibit interaction with ESR1 and ER-coactivation activity. Localizes mainly in the nucleus; when associated with A-167.
Inhibits interaction with ESR1 and ER-coactivation activity.
Strongly reduces phosphorylation but does not interfere with its NES-dependent nuclear export; when associated with A-16; A-63; A-67 and A-137.
Strongly reduces phosphorylation but does not interfere with its NES-dependent nuclear export; when associated with A-16; A-63; A-71 and A-137.
Strongly reduces phosphorylation but does not interfere with its NES-dependent nuclear export; when associated with A-16; A-67; A-71 and A-137.
Strongly reduces phosphorylation but does not interfere with its NES-dependent nuclear export; when associated with A-63; A-67; A-71 and A-137.
Strongly reduces phosphorylation; when associated with A-16; A-63; A-67 and A-71.
Abolishes autophosphorylation activity; enhances association with pre-40S ribosomal subunits; inhibits processing of 18S-E pre-rRNA to the mature 18S rRNA.
Decreases binding to unmethylated CpG islands.
Slightly decreases binding to unmethylated CpG islands.
Sterile alpha motif domain-containing protein 1
Strongly decreases binding to unmethylated CpG islands. Abolishes interaction with KDM1A.
Globular or compact configuration stabilized by disulfide bonds
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.
Methyl-CpG binding and interaction with HDAC1
No effect on autosumoylation, nor on ZNF131 sumoylation.
Required for interaction with histone H3
Loss of E3 ubiquitin-protein ligase activity.
Maintains GTPase activity. Increases interaction with PSCD1.
Suppresses GTPase activity. Decreases interaction with PSCD1.
Conserved cysteine within steroid binding domain
In CBG deficiency; Leuven; decreased cortisol-binding affinity.
In CBG deficiency; Lyon; decreased cortisol-binding affinity.
Abolishes the interaction with CCNF. Lack of proteasomal degradation. Increase in the cellular concentration of dATP and dGTP, but not dCTP and dTTP, leading to an imbalance in dNTP pools and genome instability.
Enhances inhibitory effect on Wnt signaling.
Prevents inhibitory effect on Wnt signaling.
Ribonucleoside-diphosphate reductase subunit M2
Strongly reduces the interaction with CCNF. Lack of proteasomal degradation. Increase in the cellular concentration of dATP and dGTP, but not dCTP and dTTP, leading to an imbalance in dNTP pools and genome instability.
BMP and activin membrane-bound inhibitor homolog
U1 small nuclear ribonucleoprotein 70 kDa
Major facilitator superfamily domain-containing protein 4A
Ankyrin repeat domain-containing protein 35
Abolishes binding to phosphatidylinositol 3-phosphate.
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.
Binds predominantly to PtdIns(P5) and weaker to PtdIns(P3) abd PtdIns(P4); involved in neurite outgrowth regulation
In a patient with diffuse large B-cell lymphoma; unknown pathological significance.
Found in a patient with intellectual disability and facial dysmorphisms.
In COH1; accelerates differentiation of adipose cells; response to insulin is abnormal..
In COH1; disrupts protein localization to the perinuclear region; Golgi stacks are fragmented, early endosomes are abnormal, lysosomes are enlarged and glycosylation is defective; leads to an accumulation of liquid droplets and accelerates differentiation of adipose cells; response to insulin is abnormal..
In COH1; early endosomes are abnormal, lysosomes are enlarged and glycosylation is defective.
In COH1; glycosylation is defective; accelerates differentiation of adipose cells.
In COH1; leads to an accumulation of liquid droplets and accelerates differentiation of adipose cells; response to insulin is abnormal..
In COH1; unknown pathological significance.
Intermembrane lipid transfer protein VPS13B
Localizes the protein to the Golgi apparatus
Rap guanine nucleotide exchange factor 6
Abolishes acetylation of the protein, leading to impaired transcription factor activity. Impaired subcellular location.
Does not affect acetylation of the protein.
Does not affect transcription factor activity.
In HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6.
In HOS; extensive upper limb malformations; strongly reduced affinity for DNA.
In HOS; significant cardiac malformations but only minor skeletal abnormalities; reduced protein stability and strongly reduced affinity for DNA.
Probable disease-associated variant found in a patient with atrial fibrillation; reduces transcriptional activity; affects transcriptional regulation of NKX2-5 or GATA4.
Probable disease-associated variant found in a patient with atrial fibrillation; reduces transcriptional activity; affects transcriptional regulation of NKX2-5.
Probable disease-associated variant found in a patient with sporadic dilated cardiomyopathy; associated with disease susceptibility; associated with significantly decreased transcriptional activity.
Probable disease-associated variant found in patients with familial dilated cardiomyopathy; associated with disease susceptibility; associated with significantly decreased transcriptional activity.
In RP77; decreased protein levels; does not affect localization to endoplasmic reticulum.
In RP77; decreased protein levels; does not affect localization to endoplasmic reticulum; loss of rod photoreceptor function shown by a mouse knockin model of the mutation.
In RP77; unknown pathological significance.
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.
Necessary and sufficient for interaction with IDAS and CDT1
Cleavage and polyadenylation specificity factor subunit 2
Does not inhibit histone 3'-end processing.
In FADS4; decreased localization to the nuclear pore complex; decreased interaction with NUP214 and NUP62.
In FADS4; no effect on localization to the nuclear pore complex; no effect on interaction with NUP214 and NUP62.
Protein kinase C and casein kinase substrate in neurons protein 1
Reduces membrane-binding. Abolishes membrane tubulation.
Tryptophan synthase beta chain-like PALP
LON peptidase N-terminal domain and RING finger protein 1
Found in patients with autosomal dominant nocturnal frontal lobe epilepsy; unknown pathological significance; results in decreased protein levels; decreased protein secretion.
Amyloid-beta A4 precursor protein-binding family B member 3
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.
Proprotein convertase subtilisin/kexin type 5
Amyloid beta A4 precursor protein-binding family B member 1-interacting protein
Mas-related G-protein coupled receptor member X3
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1
Hematopoietic lineage cell-specific protein
In DBA18; unknown pathological significance.
Abolishes protein-lysine N-methyltransferase activity.
Reduces protein-lysine N-methyltransferase activity.
In SCN8; decreased granulocyte proliferation; delayed granulocytic differentiation; impaired signaling; induced autophagy.
In SCN8; decreased granulocyte proliferation; increased apoptosis.
In SCN8; decreased granulocyte proliferation; induced autophagy.
In SCN8; decreases expression levels; decreases GTPase activity; decreases neutrophil numbers and migration capacity.
In SCN8; decreases expression levels; decreases neutrophil numbers and migration capacity; faster dissociation of the interaction with the SRP receptor subunit SRPRA; reduced SR compaction; impaired interaction with SR; impaired detachment from ribosome; effects on enzymatic activity are unclear as both normal and reduced GTPase activity have been reported.
In SCN8; decreases expression levels; slightly decreases GTPase activity; decreases neutrophil numbers and migration capacity; decreased granulocyte proliferation; delayed granulocytic differentiation; impaired signaling; increased apoptosis; induced autophagy.
Signal recognition particle subunit SRP54
26S proteasome non-ATPase regulatory subunit 5
Golgi apparatus membrane protein TVP23 homolog A
Nuclear pore complex-interacting protein family member A7
Nuclear pore complex-interacting protein family member A8
25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial
Abolishes interaction with PTPN11/SHP2 and phosphorylation of PTPN11/SHP2.
Important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand
In acute lymphoblastic leukemia patients and acute myelogenous leukemia patients; somatic mutation; constitutively activated.
In acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated.
In acute lymphoblastic leukemia patients; somatic mutation.
No significant effect on tyrosine phosphorylation. Abolishes activation of STAT5A.
Receptor-type tyrosine-protein kinase FLT3
Reduced phosphorylation of the wild-type kinase in response to ligand binding. No effect on the phosphorylation of the constitutively activated mutant kinase variants. Abolishes activation of STAT5A.
Cell growth regulator with RING finger domain protein 1
In MTS; disrupts the assembly of the heterohexamer with TIMM13.
Mitochondrial import inner membrane translocase subunit Tim8 A
Dendritic cell-specific transmembrane protein-like
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.
50% decrease in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1197. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1092.
Abolishes autophosphorylation and activation of downstream kinases.
Decreases intramolecular interactions and facilitates EGF binding.
Decreases intramolecular interactions and facilitates EGF binding. Increased EGF binding; when associated with A-587; A-590 and A-609.
Found in a lung cancer sample; constitutively activated kinase with higher levels of basal autophosphorylation; more sensitive to gefitinib than wild-type.
Found in a lung cancer sample; increased kinase activity.
Found in a lung cancer sample; more sensitive to gefitinib than wild-type.
Found in a lung cancer sample; somatic mutation; constitutively activated enzyme with strongly increased kinase activity; more sensitive to gefitinib than wild-type.
Found in a lung cancer sample; somatic mutation; strongly increased kinase activity; constitutively activated kinase with higher levels of basal autophosphorylation; more sensitive to gefitinib than wild-type.
Important for dimerization, phosphorylation and activation
In NISBD2; loss of function; the mutant does not localize to the cell membrane; has diffuse cytoplasmic localization.
Increased EGF binding; when associated with A-587; A-590 and A-609.
Increased EGF binding; when associated with A-590 and A-609.
N-linked (GlcNAc...) (complex) asparagine; atypical; partial
No change in interaction with PIK3C2B. 65% decrease in interaction with PIK3C2B; when associated with F-1016. Abolishes interaction with PIK3C2B; when associated with F-1092 and F-1016.
No change in interaction with PIK3C2B. Abolishes interaction with PIK3C2B; when associated with F-1197 and F-1016.
Strongly decreases interaction with CBLC.
Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-275. Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-287.
Strongly reduced autophosphorylation and activation of downstream kinases; when associated with A-309.
Variant EGFR vIII; found in a lung cancer sample; somatic mutation; induces lung cancer when exogenously expressed.
Phosphatidylinositol 4-phosphate 5-kinase type-1 beta
Changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency.
Found in a patient with schizophrenia; unknown pathological significance.
Found in patients with schizophrenia; unknown pathological significance.
Functional determinant of NMDA receptors
In DEE46; gain-of-function mutation that potentiates ionotropic glutamate receptor signaling; mutant receptors are activated by lower concentrations of glutamate and glycine and show slower deactivation after agonist removal as well as decreased sensitivity to allosteric inhibitors indicating that NMDA glutamate receptor activity is changed.
Increased glutamate and glycine agonist potency.
In VUR3; increased levels of the mutant protein that is associated with increased suppression of CTNNB1 signaling of the Wnt pathway compared to wild-type.
In MRD10; significantly reduced ability to bind GRIA1 or GRIA2 AMPARs; cell surface expression of GRIA1 is reduced in transfected hippocampal neurons and HEK293 cells producing mutant protein compared to cells producing the wild-type.
Voltage-dependent calcium channel gamma-2 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.
Benign variant; decreases steroid 11-beta-hydroxylase activity.
In AH4; abolishes steroid 11-beta-hydroxylase activity.
In AH4; almost abolishes steroid 11-beta-hydroxylase activity.
In AH4; classic; abolishes steroid 11-beta-hydroxylase activity.
In AH4; classic; highly decreases steroid 11-beta-hydroxylase activity.
In AH4; decreases steroid 11-beta-hydroxylase activity.
In AH4; high reduction of steroid 11-beta-monooxygenase activity.
In AH4; highly decreases steroid 11-beta-hydroxylase activity.
In AH4; non-classic; almost abolishes steroid 11-beta-hydroxylase activity.
In AH4; non-classic; decreases steroid 11-beta-hydroxylase activity.
In AH4; non-classic; highly decreases steroid 11-beta-hydroxylase activity.
In AH4; slightly decreases steroid 11-beta-hydroxylase activity.
In AH4; unknown pathological significance.
Coiled-coil-helix-coiled-coil-helix domain-containing protein 2
In PARK22; does not affect subcellular location.
In PARK22; unknown pathological significance; does not affect subcellular location.
May influence risk for Lewy body disorders.
In HMN2A; no effect on cytoskeleton architecture; no effect on cytoplasmic location; increased interaction with BAG3.
In HMN2A; no effect on cytoskeleton architecture; no effect on cytoplasmic location; no effect on interaction with BAG3.
In HMN2A; strengthen interaction with HSPB1.
In HMN2A; strengthen interaction with HSPB1; no effect on cytoskeleton architecture; no effect on cytoplasmic location; increased interaction with BAG3.
Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma
Increases BBS4, BBS8 and BBS9 ciliary localization.
Leucine zipper transcription factor-like protein 1
T-complex protein 1 subunit theta-like 2
In ADTKD4; affects ER translocation and processing of nascent preprorenin, resulting in abolished prorenin and renin biosynthesis and secretion.
Disintegrin and metalloproteinase domain-containing protein 32
Probable 18S rRNA (guanine-N(7))-methyltransferase
Resistant to down-regulation in response to TNF and IFNG combined treatment and effective coactivator for NR3C1, even in the presence of TNF and IFNG; when associated R-180.
Resistant to down-regulation in response to TNF and IFNG combined treatment and effective coactivator for NR3C1, even in the presence of TNF and IFNG; when associated R-196.
(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
Zinc finger SWIM domain-containing protein 3
Phosphomimetic mutant; abolishes the intramolecular interaction between the DENN domain and the C-terminus of the protein.
Ubiquitin carboxyl-terminal hydrolase 17-like protein 22
Electroneutral sodium bicarbonate exchanger 1
In isoform 4, isoform 5, isoform 7 and isoform 8.
Strongly reduced affinity for MAPK14. Almost abolishes enzyme activity with MAPK14.
Decreases interaction with NFATC2. Decreases interaction with NFATC2; when associated with N-22. Decreases interaction with NFATC2; when associated with N-22 and S-43. Markedly decreases interaction with NFATC2; when associated with T-30; S-31 and S-43. Markedly decreases interaction with NFATC2; when associated with N-22; T-30 and S-31. Impairs interaction with NFATC2; when associated with N-22; T-30, S-31 and S-43.
Does not affect interaction with NFATC2. Decreases interaction with NFATC2; when associated with 53-L--S-56. Decreases interaction with NFATC2; when associated with S-43 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with T-30 and S-31 and 53-L--S-56. Impairs interaction with NFATC2; when associated with T-30; S-31; S-43 and 53-L--S-56.
Does not affect interaction with NFATC2. Decreases interaction with NFATC2; when associated with N-22 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with T-30; S-31 and 53-L--S-56. Impairs interaction with NFATC2; when associated with N-22; T-30; S-31 and 53-L--S-56.
Does not affect interaction with NFATC2; when associated with A-36 and A-38. Attenuates inhibition by AKT; when associated with A-36 and A-38.
Does not affect interaction with NFATC2; when associated with A-36 and A-52. Attenuates inhibition by AKT; when associated with A-36 and A-52.
Does not affect interaction with NFATC2; when associated with A-38 and A-52. Attenuates inhibition by AKT; when associated with A-38 and A-52.
Markedly decreases interaction with NFATC2; when associated with S-43 and 53-L--S-56. Markedly decreases interaction with NFATC2; when associated with N-22 and 53-L--S-56. Impairs interaction with NFATC2; when associated with N-22; S-43 and 53-L--S-56.
Loss of autolysis-mediated degradation upon UV irradiation. No effect on catalytic activity.
Loss of catalytic activity including autolysis.
Strongly reduces interaction with WDR48 and activation by WDR48.
Ubiquitin carboxyl-terminal hydrolase 1, N-terminal fragment
Abolishes RNA 2'-O-methyltransferase activity; when associated with A-117 and A-157.
Abolishes RNA 2'-O-methyltransferase activity; when associated with A-31 and A-117.
Abolishes RNA 2'-O-methyltransferase activity; when associated with A-31 and A-157.
pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3
Abolishes nucleosome binding activity of a minimal SUZ12-RBBP4-AEBP2-JARID2 PRC2 complex.
In DIDDF; unknown pathological significance.
Sufficient for interaction with the PRC2 complex
Does not inhibit RNA-binding to the stem-loop structure.
Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-104.
Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-92.
Inhibits 3'-end histone mRNA exonuclease activity.
Inhibits RNA-binding to the stem-loop structure and 3'-end histone mRNA exonuclease activity.
Inhibits RNA-binding to the stem-loop structure.
Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-111.
Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-112.
Reduces slightly RNA-binding to the stem-loop structure.
Reduces slightly RNA-binding to the stem-loop structure; when associated with A-109.
Reduces slightly RNA-binding to the stem-loop structure; when associated with A-110.
Calcium permeable stress-gated cation channel 1
6-fold decrease in DNA-binding affinity.
Essential for ESRRB transcriptional activity and interaction with NCOA3
In DFNB35; uncertain pathological significance.
Coiled-coil domain-containing protein 78
Ras-related C3 botulinum toxin substrate 3
Reduced FBXL19-mediated ubiquitination and subsequent degradation.
Golgi associated RAB2 interactor protein-like Rab2B-binding
Golgi-associated RAB2 interactor protein 1B
NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial
Abolishes binding to phosphatidylinositol 3-phosphate, but not to phosphatidylinositol 4,5-bisphosphate; when associated with A-287.
Abolishes membrane tubulation activity. Abolishes binding to phosphatidylinositol 3-phosphate, but not to phosphatidylinositol 4,5-bisphosphate; when associated with A-313.
Abolishes membrane tubulation activity; when associated with E-522.
Abolishes membrane tubulation activity; when associated with E-528.
Exhibits some galactosyltransferase activity; when associated with D-440; M-451; Q-452 and V-453 in a chimeric construct with COLGALT1.
Exhibits some galactosyltransferase activity; when associated with D-440; R-450; M-451 and Q-452 in a chimeric construct with COLGALT1.
Exhibits some galactosyltransferase activity; when associated with D-440; R-450; M-451 and V-453 in a chimeric construct with COLGALT1.
Exhibits some galactosyltransferase activity; when associated with D-440; R-450; Q-452 and V-453 in a chimeric construct with COLGALT1.
Inactive glycosyltransferase 25 family member 3
No effect on lack of galactosyltransferase activity in a chimeric construct with COLGALT1. Exhibits some galactosyltransferase activity; when associated with R-450; M-451; Q-452 and V-453 in a chimeric construct with COLGALT1.
Potassium voltage-gated channel subfamily D member 1
Pleckstrin homology domain-containing family F member 1
Leucine-rich repeat-containing protein 46
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.
In M5 mutant; impaired association with Rag GTPases.
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.
Abolishes amino acid transport activity.
Complete loss of amino acid transport activity.
Decreased amino acid transport activity.
Does not affect amino acid transport activity.
In CSNU; complete loss of amino acid transport activity.
In CSNU; decreased amino acid transport activity.
In CSNU; impairs protein stability and dimer formation.
In CSNU; partial loss of amino acid transport activity.
In CSNU; severe loss of amino acid transport activity.
In CSNU; severe loss of amino acid transport activity; no effect on localization to the apical membrane.
In CSNU; type III; decreased amino acid transport activity.
In CSNU; type III; impairs protein stability and dimer formation.
In CSNU; type III; partial loss of amino acid transport activity.
In CSNU; type III; severe loss of amino acid transport activity.
In CSNU; unknown pathological significance.
Markedly reduces amino acid transport activity.
No effect on amino acid transport activity.
Slightly decreased amino acid transport activity.
Interferon-stimulated gene 20 kDa protein
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.
Cilia- and flagella-associated protein 74
In CILD49; unknown pathological significance.
In KTCN1; unknown pathological significance.
In KTCN1; unknown pathological significance; also in a patient with retinal dysfunction.
Decreased interaction with ATG2A. Loss of interaction with ATG2A; when associated with A-15.
Decreased interaction with ATG2A. Loss of interaction with ATG2A; when associated with A-17.
In NBIA5; unknown pathological significance.
Loss of interaction with AMPK. No effect on interaction with ATG2A.
WD repeat domain phosphoinositide-interacting protein 4
May confer susceptibility to obesity; reduces the ability to activate melanocortin receptor 4.
In DEE16; loss of function mutation; impairs the interaction with ARF6; overexpression of the mutant protein in primary cortical neurons abolishes the ability to increase neurite length and arborization.
In DOORS; unknown pathological significance.
In EPRPDC; results in synaptic vesicle trafficking defects when expressed in a heterologous system; does not affect localization to presynapse when expressed in a heterologous system.
In EPRPDC; unknown pathological significance.
In FIME; does not affect the interaction with ARF6; fails to induce neurite overgrowth when overexpressed in primary cortical neurons.
In FIME; fails to induce neurite overgrowth when overexpressed in primary cortical neurons.
In FIME; significantly impairs the interaction with ARF6; partially induces neurite overgrowth when overexpressed in primary cortical neurons.
UBAP1-MVB12-associated (UMA)-domain containing protein 1
Breakpoint for translocation to form RUNX1-MACROD1
No significant effect on enzyme activity.
Reduced enzyme activity. No significant effect on affinity for substrate.
Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-174. Reduces O-acetyl-ADP-ribose deacetylase activity by 93%; when associated with A-174. No significant effect on affinity for substrate.
Slightly reduced ADP-ribosyl hydrolase activity; when associated with A-184. Reduces O-acetyl-ADP-ribose deacetylase activity by 93%; when associated with A-184. No significant effect on affinity for substrate.
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.
Fine-tunes the proton-transfer properties of H-64
Fine-tunes the proton-transfer properties of H-64; involved in the binding of some activators, including histamine and L-histidine
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.
Involved in the binding of some activators, including histamine and L-histidine
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.
Impaired trafficking to the cell surface.
Strongly reduces Wnt inhibitory function.
N-linked (GlcNAc...) asparagine; in KEL2 antigen
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.
In OSTEOP; associated with disease susceptibility.
Found in a patient with a Cowden-like phenotype; unknown pathological significance; associated with increased manganese superoxide dismutase expression and normal levels of reactive oxygen species; associated with a 1.2-fold increase in AKT expression and 1.3-fold change in MAPK expression.
Found in a patient with a Cowden-like phenotype; unknown pathological significance; associated with increased manganese superoxide dismutase function and increased levels of reactive oxygen species; associated with a 2.7-fold change in AKT expression and a 1.7-fold increase in MAPK expression.
In MC2DN4; decreased succinate dehydrogenase (ubiquinone) activity in homozygous patient cells; decreased protein levels in homozygous patient cells.
In MC2DN4; decreased succinate dehydrogenase (ubiquinone) activity; decreased protein levels in homozygous patient cells.
In MC2DN4; unknown pathological significance.
In PCC; absence of expression in tumor cells indicating complete loss of SDHB function.
Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
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.
In MFM8; also found in a patient with limb-girdle muscular dystrophy; decreased function in cellular response to oxidative stress; no effect on subcellular location in the nucleus and sarcomere. Overexpression in C2C12 cells leads to reduced cell proliferation, migration and differentiation..
In MFM8; decreased function in cellular response to oxidative stress; no effect on subcellular location at nucleus and sarcomere.
Pyridine nucleotide-disulfide oxidoreductase domain-containing protein 1
Zinc finger C2HC domain-containing protein 1B
Diminishes ability to promote MHC-I internalization.
Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members
Found in patients with isolated congenital asplenia; unknown pathological significance; does not affect DNA binding; impairs transactivation activity.
In ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired.
In CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding.
In VSD3; significantly reduced activation of NPPA gene compared to wild-type.
32 X 5 AA repeats of C-C-[CGSVRQH]-[SQTNP]-[PTSI]
Constitutive coactivator of peroxisome proliferator-activated receptor gamma
Alanine--glyoxylate aminotransferase 2, mitochondrial
Associated with an increased risk for coronary heart disease (CHD) in smoker and diabetic mellitus (DM) patients in a Chinese population; higher plasma symmetric (SDMA) dimethylarginine as well as plasma and urinary beta-aminoisobutyrate (BAIB) concentrations; localized to the mitochondrion as the wild-type; reduces alanine-glyoxylate aminotransferase activity.
Higher plasma and urinary beta-aminoisobutyrate (BAIB) concentrations.
RUN and FYVE domain-containing protein 2
Does not affect localization to the cell membrane. Abolishes T3 uptake activity.
Does not alter kinetic characteristics of thyroid hormone (TH) transport.
In MCT8 deficiency; atypical form; characterized by developmental delay hypotonia and delayed myelination.
In MCT8 deficiency; decreased thyroid hormone transport; decreased protein abundance; decreased localization to the plasma membrane.
In MCT8 deficiency; does not affect homodimerization activity.
In MCT8 deficiency; does not affect homodimerization activity; impaired thyroid hormone transporter activity; impaired localization to the cell membrane.
In MCT8 deficiency; impaired homodimerization.
In MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane.
In MCT8 deficiency; impaired thyroid hormone transporter activity; impaired localization to the cell membrane.
In MCT8 deficiency; increased homodimerization activity.
In MCT8 deficiency; loss of thyroid hormone transport.
In MCT8 deficiency; results in a mild clinical phenotype; retains some residual thyroid hormone transporter activity.
No effect on thyroid hormone (TH) transport.
No effect on thyroid hormone transport. No effect on protein abundance. No effect on protein localization to the plasma membrane.
Reduction of thyroid hormone (TH) transport.
Found in patients with severe infantile epileptic encephalopathy; unknown pathological significance.
GPI ethanolamine phosphate transferase 3
In HPMRS2; decrease in mannose-ethanolamine phosphotransferase activity.
In HPMRS2; decrease in mannose-ethanolamine phosphotransferase activity; decreased protein expression.
In HPMRS2; decrease in mannose-ethanolamine phosphotransferase activity; decreased protein expression; unknown pathological significance.
In HPMRS2; decrease in mannose-ethanolamine phosphotransferase activity; increased protein expression.
In HPMRS2; unknown pathological significance.
Probable disease-associated variant found in a patient with epileptic encephalopathy; decrease in mannose-ethanolamine phosphotransferase activity; decreased protein expression.
Decreases catalytic activity to 11 percent of wild type.
Decreases catalytic activity to 13 percent of wild type.
Decreases catalytic activity to 26 percent of wild type.
Decreases catalytic activity to 4 percent of wild type.
Decreases catalytic activity to 5 percent of wild type.
Decreases catalytic activity to 6 percent of wild type.
Inactive serine/threonine-protein kinase VRK3
Reduces phosphorylation but does not affect nuclear localization.
Sumoylation reduced to 40% of wild-type.
Sumoylation reduced to 42% of wild-type.
Sumoylation reduced to 43% of wild-type.
Sumoylation reduced to 44% of wild-type.
Sumoylation reduced to 46% of wild-type.
Sumoylation reduced to 53% of wild-type.
Sumoylation reduced to 57% of wild-type.
Sumoylation reduced to 62% of wild-type.
Sumoylation reduced to 68% of wild-type.
In PBD11B; neonatal adrenoleukodystrophy.
G-protein coupled receptor family C group 5 member C
G-protein coupled receptors family 3 profile
Does not affect its subcellular distribution.
In isoform 2, isoform 4, isoform 6, isoform 9 and isoform 11.
In isoform 3, isoform 4, isoform 7, isoform 8 and isoform 9.
Necessary for nuclear and nucleolar localization
Necessary for nuclear localization and for nucleolar accumulation in response to heat shock
Reduces its nuclear and nucleolar accumulation. Increases its cytoplasmic accumulation.
Decreased phosphorylation. Increased localization to lysosome.
In TNZD; decreased protein abundance; increased protein aggregation; no dominant negative effect.
In TNZD; decreased zinc ion import into organelle; dominant negative effect; changed protein localization; retained in endoplasmic reticulum and Golgi; dominant negative effect; results in decreased zinc secretion in milk.
Loss of interaction with AP3D1. Loss of localization to lysosome.
Loss of localization to mitochondrial inner membrane. Loss of function in zinc ion import into mitochondrion.
Serine/threonine-protein kinase MRCK gamma
Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5
In allele NDOR1*1; shows a decrease in affinity for NADPH and a reduction in ferricyanide reductase activity.
NADPH-dependent diflavin oxidoreductase 1
In HH16; phenotype consistent with Kallmann syndrome.
In HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Asp-217 in KAL1.
In HH16; phenotype consistent with Kallmann syndrome; digenic; found in a patient also carrying mutation Cys-268 in PROKR2.
In HH16; phenotype consistent with Kallmann syndrome; digenic; found in patients also carrying mutation Cys-268 in PROKR2 or mutation Arg-687 in FGFR1.
In HH16; unknown pathological significance.
Abrogates interaction with AKTIP, VPS16, VPS18, VPS39 and VPS41, AP4M1, FHIP1B, decreases interaction with HOOK2 but does not affect interaction withHOOK3; when associated with 661-A-A-662.
Abrogates interaction with AKTIP, VPS16, VPS18, VPS39 and VPS41, AP4M1, FHIP1B, decreases interaction with HOOK2 but does not affect interaction withHOOK3; when associated with 669-A-A-670.
Sufficient for homodimerization, interaction wit HOOK2, HOOK3 and AP4M1
Sufficient for interaction with AKTIP and VPS18
Sufficient for interaction with microtubules
Coiled-coil and C2 domain-containing protein 2A
In JBTS9; digenic inheritance; the patient also carries mutation C-360 in CEP41.
In JBTS9; unknown pathological significance.
In MKS6; unknown pathological significance.
Loss of inhibition of autophagosome formation; when associated with A-472.
Loss of inhibition of autophagosome formation; when associated with A-508.
Abolishes proteolytic processing. Abolishes interaction with WNT5A and ability to regulate Wnt signaling. Increases binding of hedgehog protein SHH to the PTC1 receptor and abolishes ability to inhibit hedgehog signaling.
Interchain (between alpha and beta chains)
Breakpoint for translocation to form PCM1-JAK2 fusion protein
Breakpoint for translocation to form PCM1-RET fusion protein
Pericentriolar material 1 protein C-terminal
Loss of dimerization; when associated with P-176.
Loss of dimerization; when associated with P-183.
PTB domain-containing engulfment adapter protein 1
In DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect.
In DFNA3A; the mutant is targeted to the plasma membrane but fails to transfer ionic calcium or propidium iodide intercellularly suggesting disruption of both ionic and biochemical coupling; heterozygous gap junctions also show dysfunctional intercellular couplings and hemichannel opening confirming the dominant-negative nature of the mutation.
In DFNB1A; does not form gap junctions since the mutated protein is confined in the cytoplasm and not transported to the cell membrane; when the mutation is coexpressed with the wild-type protein ionic and biochemical coupling is normal consistent with the recessive nature of the mutation.
In DFNB1A; it is correctly synthesized and targeted to the plasma membrane; it inefficiently forms intercellular channels that display an abnormal electrical behavior.
In DFNB1A; sorted to the plasma membrane normally and forms gap junctions that were morphologically and electrically indistinguishable from those of control; the mutation reduces the permeability of GJB2 gap junction channels to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), resulting in blockade of the Ins(1,4,5)P3-induced inward calcium current in neighboring cells.
In DFNB1A; the mutant disrupts cellular communication.
In PPKDFN and DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect.
In PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein.
In PPKDFN; the mutant has a dominant-negative effect on connexin trafficking.
In PPKDFN; the mutant protein completely prevents the formation of functional channels.
In VOWNKL and PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein.
In a patient with congenital erythrokeratodermia; unknown pathological significance.
Loss of gap junction ion conductance, probably due to very low open probability of the channels. Can form functional channels with wild-type, but with strongly reduced channel conductance. No visible effect on channel assembly and membrane insertion.
Strongly reduced insertion into the cell membrane and strongly reduced gap junction plaque assembly.
Impaired localization leading to localization to the endoplasmic reticulum.
Probable loss of protein-cysteine S-palmitoyltransferase activity. Loss of function in the TRAIL-activated apoptotic signaling pathway.
Probable loss of protein-cysteine S-palmitoyltransferase activity. Loss of function in the TRAIL-activated apoptotic signaling pathway. No effect on binding of the TNFRSF10A substrate.
Break repair meiotic recombinase recruitment factor 1
Protein phosphatase 1 regulatory subunit 3G
Decreased estrone and 16alpha-hydroxyestrone glucuronosyltransferase activity.
Increased estriol, 17-epiestriol and 16alpha-hydroxyestrone glucuronosyltransferase activity. Decreased of estrone and 16-epiestriol glucuronosyltransferase activity.
Loss of estrone and 16alpha-hydroxyestrone glucuronosyltransferase activity.
ATP-binding cassette sub-family A member 13
In isoform 4, isoform 5, isoform 6 and isoform 7.
Zinc finger and SCAN domain-containing protein 21
4 X 9 AA tandem repeats, potential spacer function
In SPGF56; unknown pathological significance.
Abolished ability to promote ubiquitination of target proteins such as GLI1.
Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus.
Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-131.
Abolished binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-82.
Does not affect cleavage by a caspase-3-like protease.
Prevents cleavage by a caspase-3-like protease.
Strongly reduced binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-163.
Strongly reduced binding to -Gly-Leu-Asp-Arg C-degron at the C-terminus; when associated with A-193.
Abolishes localization to the Flemming body and ability to delay abscission.
In HH11; the patient also carries a mutation in FGFR1.
In HH11; unequivocal evidence of impaired receptor signaling.
May contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in FGFR1.
May contribute to hypogonadotropic hypogonadism in patients carrying disease-causing mutations in SPRY4 or KAL1.
Ciliogenesis and planar polarity effector 1
In OFD6; unknown pathological significance.
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 binding to 6'-sulfo sialyl-Lewis X.
Indispensable role in 6'-sulfo sialyl-Lewis X
Minor effects on binding to 6'-sulfo sialyl-Lewis X.
Modestly affected binding to 6'-sulfo sialyl-Lewis X.
Strongly impaired binding to 6'-sulfo sialyl-Lewis X.
Required for nuclear location and interaction with MOV10
Does not affect production of 150-200 kDa subunit.
Macrophage colony-stimulating factor 1 43 kDa subunit
Processed macrophage colony-stimulating factor 1
Produces biologically active protein which is secreted.
Abolishes regulation of channel activity.
Decreases protein stability. Causes conformation changes that impair interaction with the alpha subunit.
In LQT10; increase in late sodium current.
Insulin-like growth factor-binding protein 1
In DFNA1; with thrombocytopenia; affects function in regulation of cytoskeleton organization.
Substantial loss of phosphorylation, no increase of phosphorylation in response to cAMP, increased stability, reduced interaction with OSBPL2 and OSBPL10 and reduced mitochondrial movement.
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..
Cilia- and flagella-associated protein 206
Mediates microtubule-binding and homooligomerization
Neural proliferation differentiation and control protein 1
Putative tyrosine carboxypeptidase MATCAP2
In SMCD and spondylometaphyseal dysplasia Japanese type.
Does not affect interaction with TERF1. Remains associated with TERF1 at the telomere in late prometaphase cells.
Prevents the localization of TERF1 to the centrosome.
U6 snRNA-associated Sm-like protein LSm8
Impairs phospholipid-binding, targeting to membrane and vesicle-binding; when associated with S-698.
Impairs phospholipid-binding, targeting to membrane and vesicle-binding; when associated with S-701.
Baculoviral IAP repeat-containing protein 1
Prevents the proper cleavage of pro-CASP9, but does not inhibit the cleavage of pro-CASP3 by CASP9.
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
Anaphase-promoting complex subunit 4 long
Impairs UBE2S-mediated polyubiquitination, decreasing substrate affinity. Does not affect UBE2C-mediated multiubiquitination.
Probable E3 ubiquitin-protein ligase DTX2
Abolished ability mediate double-strand break repair; impaired nuclear localization.
Abolished ability to bridge DNA; when associated with E-72 and E-99.
Abolished cleavage by caspase and ability to regulate phospholipid scramblase activity.
Abolished interaction with NHEJ1/XLF; when associated with E-4 or E-26 or E-65 or E-71 or E-72. Abolished ability to bridge DNA; when associated with E-65. Abolished ability to bridge DNA; when associated with E-72 and E-90.
Abolished interaction with NHEJ1/XLF; when associated with E-65.
Abolished interaction with NHEJ1/XLF; when associated with E-99.
Abolished interaction with NHEJ1/XLF; when associated with E-99. Abolished ability to bridge DNA; when associated with E-90 and E-99.
Abolished nuclear localization of XRCC4 and LIG4. Impaired ability to repair DNA double-strand breaks (DSBs). Reduced ubiquitination by the SCF(FBXW7) complex caused by impaired localization to the nucleus.
Abolished phosphorylation by CK2, leading to strongly reduced interaction with PNKP.
Abolished ubiquitination by the SCF(FBXW7) complex.
Abolishes sumoylation. 5-fold decrease in recombination efficiency. Does not affect nuclear localization of XRCC4 and LIG4.
Does not affect ability mediate double-strand break repair.
Does not affect ability mediate double-strand break repair. In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-304, D-315, D-320, D-323 and D-327.
Does not affect ability mediate double-strand break repair. In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-304, D-315, D-320, D-323 and D-328.
Does not affect ability mediate double-strand break repair. In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-304, D-315, D-320, D-327 and D-328.
Does not affect ability to localize into the nucleus.
Does not affect interaction with NHEJ1/XLF.
Does not affect ubiquitination by the SCF(FBXW7) complex.
Impaired ability mediate double-strand break repair.
Impaired ability to localize in the nucleus, without affecting ability to activate phospholipid scramblase activity of XKR4.
Impaired ability to localize in the nucleus.
In 2DA; abolished cleavage by caspase and ability to regulate phospholipid scramblase activity.
In SSMED; impaired ability to repair DNA double-strand breaks.
In SSMED; impairs the protein function in DNA double-strand break repair.
In SSMED; no expression of the protein is observed; complete loss of function in DNA double-strand break repair.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-304, A-315, A-320, A-323 and A-327.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-304, A-315, A-320, A-323 and A-328.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-304, A-315, A-320, A-327 and A-328. Does not affect phosphorylation by CK2.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-304, A-320, A-323, A-327 and A-328.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-315, A-320, A-323, A-327 and A-328.
In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-260, A-304, A-315, A-320, A-323, A-327 and A-328.
In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-304, D-315, D-323, D-327 and D-328.
In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-304, D-320, D-323, D-327 and D-328.
In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-260, D-315, D-320, D-323, D-327 and D-328.
In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-193, D-304, D-315, D-320, D-323, D-327 and D-328.
In XRCC4-Asp mutant; phospho-mimetic mutant; abolished ability to bridge DNA when associated with NHEJ1/XLF phospho-mimetic mutant; when associated with D-260, D-304, D-315, D-320, D-323, D-327 and D-328.
Reduced phosphorylation by PRKDC. In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-304, A-315, A-320, A-323, A-327 and A-328.
Reduced ubiquitination by the SCF(FBXW7) complex.
Slightly reduced phosphorylation by PRKDC. In XRCC4-Ala mutant; abolished phosphorylation by PRKDC; does not affect ability to bridge DNA when associated with NHEJ1/XLF phosphorylation-defective mutant; when associated with A-193, A-260, A-304, A-315, A-323, A-327 and A-328.
Strongly decreased interaction with NHEJ1/XLF. Abolished interaction with NHEJ1/XLF; when associated with E-99. Abolished ability to bridge DNA; when associated with E-99. Abolished interaction with NHEJ1/XLF; when associated with E-102.
Sperm acrosome membrane-associated protein 6
Abolishes interaction with DDX6; when associated with A-300.
Abolishes interaction with DDX6; when associated with A-306.
In PARK11; unknown pathological significance.
Required for interaction with SARS-CoV-2 non-structural protein 2 (nsp2)
(Microbial infection) O-linked (Glc) threonine; by P.sordellii toxin TcsL
Abolished palmitoylation on Cys; reduced palmitoylation on Lys residues.
Found in a patient with Costello syndrome, exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors.
In AML; expression in 3T3 cell causes cellular transformation; expression in COS cells activates the Ras-MAPK signaling pathway; lower GTPase activity; faster GDP dissociation rate.
In CFC2 and NS3, exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein.
In CFC2; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors.
In CFC2; exhibits an increase in intrinsic and guanine nucleotide exchange factor catalyzed nucleotide exchange in combination with an impaired GTPase-activating protein-stimulated GTP hydrolysis but functional in interaction with effectors.
In GASC and JMML; also found in lung carcinoma; somatic mutation.
In GASC, JMML and OES; also found in a breast carcinoma cell line; somatic mutation.
In GASC, JMML and SFM; somatic mutation; also found in pancreatic carcinoma and lung carcinoma; also found in metastatic colorectal cancer.
In GASC; also found in bladder cancer; somatic mutation.
In GASC; also found in lung carcinoma, pancreatic carcinoma and colon cancer; also found in metastatic colorectal cancer; somatic mutation; it is constitutively activated and stimulates transcription activation of tumor suppressor genes in non-transformed fibroblasts.
In GASC; found also in a patient with Costello syndrome; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein.
In K-Ras-3KR; abolished lysine-palmitoylation.
In NS3; affects activity and impairs responsiveness to GTPase activating proteins; characterized by a strong increase of both intrinsic and guanine nucleotide exchanged factor-catalyzed nucleotide exchange leading to an increased level of the activated state.
In NS3; affects activity and impairs responsiveness to GTPase activating proteins; exhibits only minor alterations in its in vitro biochemical behavior compared to wild-type protein.
In NS3; characterized by a defective GTPase-activating protein sensitivity and a strongly reduced interaction with effectors.
In NS3; impairs GTPase-activating protein stimulated GTP hydrolysis with unaffected intrinsic functions and a virtually functional effector interaction.
In OES; somatic mutation; also found in colorectal cancer samples.
In colorectal cancer samples; somatic mutation.
In lung cancer and bladder cancer; somatic mutation.
In lung carcinoma; somatic mutation; also found in metastatic colorectal cancer.
In pylocytic astrocytoma; somatic mutation; increase activation of the Ras pathway.
N-acetylmethionine; in GTPase KRas; alternate
N-acetylthreonine; in GTPase KRas, N-terminally processed
Abolishes FUBI-ribosomal protein S30 processing. Impairs 40S ribosome biogenesis.
Abolishes FUBI-ribosomal protein S30 processing; when associated with A-73. Impairs 40S ribosome biogenesis.
Abolishes FUBI-ribosomal protein S30 processing; when associated with A-74. Impairs 40S ribosome biogenesis.
Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
More than 50% loss of FYN-mediated phosphorylation.
Abrogates the interaction with 7SK small nuclear RNA (7SK); when associated with A-50 and A-52. Does not affect interaction between HEXIM1, CDK9 and 7SK small nuclear RNA (7SK); when associated with A-50 and A-52. Does not affect interaction with MEPCE and LARP7; when associated with A-50 and A-52. Decreases induction of P-TEFb-dependent DNA damage response (DDR); when associated with A-50 and A-52.
Abrogates the interaction with 7SK small nuclear RNA (7SK); when associated with A-52 and A-54. Does not affect interaction between HEXIM1, CDK9 and 7SK small nuclear RNA (7SK); when associated with A-52 and A-54. Does not affect interaction with MEPCE and LARP7; when associated with A-52 and A-54. Decreases induction of P-TEFb-dependent DNA damage response (DDR); when associated with A-52 and A-54.
Decreases affinity for RNA binding. Abrogates the interaction with 7SK small nuclear RNA (7SK); when associated with A-50 and A-54. Does not affect interaction between HEXIM1, CDK9 and 7SK small nuclear RNA (7SK); when associated with A-50 and A-54. Does not affect interaction with MEPCE and LARP7; when associated with A-50 and A-54. Decreases induction of P-TEFb-dependent DNA damage response (DDR); when associated with A-50 and A-54.
Decreases affinity for RNA binding. Does not affect The NEXT complex assembly. Impairs snRNA binding.
Found in a patient with a form of spinal muscular atrophy; unknown pathological significance.
Impaired interaction with ZCCHC8; when associated with E-25.
Impaired interaction with ZCCHC8; when associated with E-29.
Impairs phosphorylation. Impairs phosphorylation; when associated with S-136.
Impairs phosphorylation. Impairs phosphorylation; when associated with S-204. Prevents PROMPTs accumulation to >50%.
Reduced interaction with ZCCHC8, and impaired interaction with SF3B2/SAP145; when associated with A-65.
Reduced interaction with ZCCHC8, and impaired interaction with SF3B2/SAP145; when associated with E-69.
Fails to accumulate following gamma-irradiation.
In AML; no effect on expression; no effect on DNA-binding or transactivation activity.
In AML; nuclear; no effect on expression; loss of DNA-binding and transactivation activity.
Required to functionally cooperate with SREBF1 in promoter activation
Required to induce adipocyte differentiation
Required to repress E2F1:TFDP1-mediated transcription, to inhibit cell cycle and to induce adipocyte differentiation
Cytochrome c oxidase assembly protein COX18, mitochondrial
Membrane insertase YidC/Oxa/ALB C-terminal
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
Ubiquitin carboxyl-terminal hydrolase MINDY-3
In EPM6 and MYOS; 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
Abolishes down-regulation of activated CSF1R.
Constitutive kinase activity. Loss of inhibition by imatinib.
In BANDDOS; impairs phosphorylation of JNK kinases upon stimulation with CSF1.
In HDLS1; impairs autophosphorylation upon stimulation with CSF1.
Macrophage colony-stimulating factor 1 receptor
Reduced kinase activity. Reduced interaction with SRC, FYN and YES1.
In AHC; impairs transcriptional silencing of the StAR promoter.
In AHC; results in a severe loss of repressor activity.
In AHC; the patient presents an inappropriate tall stature and renal ectopy.
Nuclear receptor subfamily 0 group B member 1
Strongly reduces homodimerization and interaction with NR0B2.
Coiled-coil domain-containing protein 115
Double-stranded RNA-binding protein Staufen homolog 1
RNA guanine-N7 methyltransferase activating subunit
Abolishes association with cytoplasmic vesicle membranes.
Abolishes interaction with WWOX. Abolishes interaction with NEDD4. Abolishes interaction with NEDD4 and impairs location at endosomes; when associated with A-61.
Decreases protein stability and association with early endosome membranes. Impaired function in targeting endocytosed proteins for lysosomal degradation.
Found as a somatic mutation in a EMPD primary tumor.
Impaired function in targeting endocytosed proteins for lysosomal degradation.
In CMT1C; decreases protein stability and association with early endosome membranes; impaired function in targeting endocytosed proteins for lysosomal degradation; does not abolish interaction with NEDD4 and TSG101.
In CMT1C; does not abolish interaction with NEDD4 and TSG101.
In one EMPD primary tumor; somatic mutation.
Lipopolysaccharide-induced tumor necrosis factor-alpha factor
No effect on interaction with WWOX. No effect on interaction with NEDD4. Abolishes interaction with NEDD4 and impairs location at endosomes; when associated with A-23.
No effect on location at endosomes, but impairs protein stability.
PSAP motif; important for interaction with TSG101
In SDS1; strongly reduced release of EIF6 from pre-60S ribosome subunits.
In SDS1; unknown pathological significance.
Ribosome maturation protein SDO1/SBDS C-terminal
Ribosome maturation protein SDO1/SBDS N-terminal
Ribosome maturation protein SDO1/SBDS central
Strongly reduced release of EIF6 from pre-60S ribosome subunits.
In DEE97; mislocalized to the cytoplasm.
In DEE97; unknown pathological significance; mislocalized to the cytoplasm.
Necessary for RNA-binding, TNNT2 exon 5 and NMDA R1 exon 21 inclusion
Low-density lipoprotein receptor-related protein 3
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.
Required and sufficient for targeting to lysosomes and lamellar bodies
Likely benign variant; associated with beta-glucuronidase pseudodeficiency with no clinical consequences; reduced activity levels.
Abolishes interaction with DYNLL1 and no effect on interaction with HMMR; when associated with 391-A--A-393 and 409-A--A-411.
Abolishes interaction with DYNLL1 and no effect on interaction with HMMR; when associated with 391-A--A-393 and 442-A--A-444.
Abolishes interaction with DYNLL1 and no effect on interaction with HMMR; when associated with 409-A--A-411 and 442-A--A-444.
Required for interaction with KIF22 and function in chromosome congression
Platelet-derived growth factor (PDGF) family profile
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.
Required for interaction with and acetylation by EP300
Zinc finger and BTB domain-containing protein 7B
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.
Elongation of very long chain fatty acids protein 6
Complete loss of lipid phosphatase activity.
Does not rescue the wortmannin-induced dilation of endosomes due to accumulation of (PtdIns(3,4)P2).
Inositol polyphosphate-4-phosphatase type I A
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.
Translational activator of cytochrome c oxidase 1
(Microbial infection) O-acetylserine; by Yersinia YopJ
(Microbial infection) O-acetylserine; by Yersinia YopJ; alternate
(Microbial infection) O-acetylthreonine; by Yersinia YopJ
Abolished ability to activate NF-kappa-B downstream of NOD2.
Abolishes interaction with NOD1. Abolished activation of NF-kappa-B.
Abolishes protein-kinase activity without preventing ability to activate NF-kappa-B downstream of NOD2.
Abolishes protein-kinase activity. Reduces FAS-mediated apoptosis.
Decreased homooligomerization and ability to transmit NOD2 signaling.
Decreased phosphorylation and activation. Abolished phosphorylation by LRRK2.
Impaired interaction with NOD2 and decreased homooligomerization and ability to transmit NOD2 signaling.
Phosphoserine; by autocatalysis and LRRK2; alternate
Prevents phosphorylation. Reduces serine and threonine phosphorylation of ARHGEF2.
Receptor-interacting serine/threonine-protein kinase 2
Reduced formation of filaments and activation of NF-kappa-B.
Reduced ubiquitination by XIAP and activation of NF-kappa-B; when associated with R-410.
Reduced ubiquitination by XIAP and activation of NF-kappa-B; when associated with R-538.
Strongly decreased activation of NF-kappa-B.
Strongly decreased activation of NF-kappa-B. Does not affect activation of NF-kappa-B; when associated with E-458.
Strongly decreased activation of NF-kappa-B. Does not affect activation of NF-kappa-B; when associated with R-445.
In isoform 3, isoform 4, isoform 6 and isoform 7.
Abolishes cleavage of Gasdermin-D (GSDMD).
In IDL(uncl); abolished cleavage in the interdomain region; when associated with 315-N-N-316.
In IDL(uncl); abolished cleavage in the interdomain region; when associated with N-297.
Loss of protease activity. Loss of SPHK2 cleavage and release in apoptotic cells.
Mediates autoprocessing but is unable to interact with Gasdermin-D (GSDMD) and mediate its cleavage.
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 COXPD39; unknown pathological significance; may affect splicing.
Ribosome-releasing factor 2, mitochondrial
Associated with susceptibility to lumbar disk disease in Japanese; increases binding and inhibition of TGFB1.
Cartilage intermediate layer protein 1 C1
Cartilage intermediate layer protein 1 C2
DBF4-type zinc finger-containing protein 2
In MEGDEL; unknown pathological significance.
Abolishes interaction with SMARCA5/SNF2H, and abolishes the formation of the CHRACISWI chromatin remodeling complex.
Abolishes interaction with the CHRAC1-POLE3 heterodimer.
Bromodomain adjacent to zinc finger domain protein 1A
Required for interaction with SMARCA5 and formation of the CHRAC ISWI chromatin remodeling complex
Required for interaction with the CHRAC1-POLE3 heterodimer. Required for interaction with the CHRAC1-POLE3 heterodimer
Abolished phosphorylation after forskolin treatment.
Abolished phosphorylation by NLK, leading to impaired inhibition of the mTORC1 complex in response to osmotic stress.
Abolishes AMPK-mediated phosphorylation; when associated with A-722. Does not affect phosphorylation after forskolin treatment.
Abolishes AMPK-mediated phosphorylation; when associated with A-792.
Decreased phosphorylation, leading to increased activity of the mTORC1 complex.
In Clw1 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex.
In Clw2 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex.
In Clw3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex.
In Clw4 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex.
In alpha24 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes.
In alpha26 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes.
In alpha29 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes.
In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with E-597 and A-635.
In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with F-560 and A-635.
In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with F-560 and E-597.
Mimics phosphorylation, leading to impaired interaction with small GTPases Rag and activation of the mTORC1 complex.
Reduced acetylation, leading to decreased activation of the mTORC complex.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-164; A-172; A-214; A-224; A-284; A-287; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-394; A-395; A-397; A-471; A-582 and A-586.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-214; A-224; A-284; A-287 and A-377.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-214; A-224; A-284; A-287 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-214; A-224; A-284; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-214; A-224; A-287; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-214; A-284; A-287; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-172; A-224; A-284; A-287; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-164; A-214; A-224; A-284; A-287; A-377 and A-575.
Almost complete loss of CDK1 phosphorylation in vitro, loss of PLK1-binding, no effect on cortical localization; when associated with A-78; A-172; A-214; A-224; A-284; A-287; A-377 and A-575.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-394; A-395; A-397; A-471 and A-582.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-394; A-395; A-397; A-471 and A-586.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-394; A-395; A-397; A-582 and A-586.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-394; A-395; A-471; A-582 and A-586.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-394; A-397; A-471; A-582 and A-586.
Drastic reduction in PLK1 phosphorylation in vitro, no effect on cortical localization; when associated with A-382; A-395; A-397; A-471; A-582 and A-586.
Mitotic interactor and substrate of PLK1
No effect on cortical localization; when associated with D-394; D-395; D-397; D-471 and D-582.
No effect on cortical localization; when associated with D-394; D-395; D-397; D-471 and D-586.
No effect on cortical localization; when associated with D-394; D-395; D-397; D-582 and D-586.
No effect on cortical localization; when associated with D-394; D-395; D-471; D-582 and D-586.
No effect on cortical localization; when associated with D-394; D-397; D-471; D-582 and D-586.
No effect on cortical localization; when associated with D-395; D-397; D-471; D-582 and D-586.
Ankyrin repeat domain-containing protein 53
In CSNB1B; abolishes expression at the cell membrane.
No effect on location at the cell membrane.
Complete loss of ubiquitination by RNF186.
Does not affect G protein alpha subunit activation.
Does not affect ability to regulate cAMP levels; when associated with A-135 and A-540.
Does not affect ability to regulate cAMP levels; when associated with A-135 and A-578.
Does not affect ability to regulate cAMP levels; when associated with A-540 and A-578.
In M1 mutant; decreased localizatiuon to the nucleus.
In M2 mutant; decreased localizatiuon to the nucleus.
In Mut1; decreased interaction with GNAO1.
In Mut2; does not affect interaction with GNAO1.
In Mut3; decreased interaction with GNAO1.
In Mut4; does not affect interaction with GNAO1.
Nearly abolished ability to inhibit the GTPase activator activity of RGS7 without affecting glycine-binding.
Nearly abolished glycine-binding and ability to inhibit the GTPase activator activity of RGS7.
Decrease in the transport capacity and substrate affinity for adenosine. Resistance to dipyridamole, dilazep, nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Decrease in the transport capacity but no change in affinity for adenosine. Resistance to dipyridamole and dilazep, little or no effect on the sensitivities to nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Decrease in the transport capacity for adenosine but no change in substrate affinity. Resistance to dipyridamole, dilazep, nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Decreased affinity for cytidine and adenosine but not uridine. Resistance to azidothymidine (AZT), dideoxyinosine (ddI), nitrobenzylmercaptopurine riboside (NBMPR), dilazep, dipyridamole and hypoxanthine but not dideoxycytidine (ddC).
Impaired protein folding and/or altered trafficking. Decrease in the transport capacity but no change in affinity for adenosine. No effect on the sensitivity to dipyridamole. Resistance to dilazep, nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Impaired protein folding and/or altered trafficking. Decrease in the transport capacity for adenosine but no change in substrate affinity. Resistance to dipyridamole, dilazep, nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Increase in the transport capacity and decrease in affinity for inosine. Increase in the transport capacity but no change in affinity for adenosine. Resistance to nitrobenzylmercaptopurine riboside (NBMPR) and dilazep but not dipyridamole.
Increase in the transport capacity but no change in affinity for adenosine. Resistance to dipyridamole and increase in the sensitivity to dilazep. Little or no effect on the sensitivities to nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
Loss of nucleobase transport; when associated with S-193; S-213; S-222; S-297; S-333; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-193; S-213; S-222; S-297; S-333; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-378; S-414 and S-416. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-378 and S-416.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-378; S-414 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-378 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-333; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-297; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-333; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-222; S-333; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-213; S-297; S-333; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-213; S-297; S-333; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-193; S-222; S-297; S-333; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-193; S-222; S-297; S-333; S-378; S-416 and S-439.
Loss of nucleobase transport; when associated with S-87; S-213; S-222; S-297; S-333; S-378; S-414; S-416 and S-439. No change in nucleobase transport; when associated with S-87; S-213; S-222; S-297; S-333; S-378; S-416 and S-439.
No change in the transport capacity but decrease in affinity for adenosine. Resistance to dipyridamole, dilazep, nitrobenzylmercaptopurine riboside (NBMPR), draflazine and soluflazine.
No effect on subcellular localization and inosine transport.
No effect on the transport activity for adenosine.
Reduction of the transport activity for adenosine.
Resistance to nitrobenzylmercaptopurine riboside (NBMPR) and dilazep but not dipyridamole.
Required for efficient interaction with KRT5 and KRT14 heterodimers
Required for interaction with intermediate filament proteins
Required for interaction with type2 keratins, DES and VIM
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.
EH domain-binding protein 1-like protein 1
In LIS1; abrogates interaction with NDE1 and reduces neuronal migration in vitro.
In LIS1; reduces neuronal migration in vitro.
In SBH; abrogates interaction with NDE1 and reduces neuronal migration in vitro.
In SBH; somatic mosaicism in 18% of lymphocytes and 21% of hair root cells.
Platelet-activating factor acetylhydrolase IB subunit beta
Required for self-association and interaction with PAFAH1B2 and PAFAH1B3
In AV; loss of ability to activate splicing. Great reduction in splice site switching activity and no effect on RNA-binding.
In FV1; loss of ability to activate splicing. Slight reduction in splice site switching activity and no effect on RNA-binding.
In FV2; loss of ability to activate splicing. Great reduction in splice site switching activity and RNA-binding.
In MR-A; loss of ability to activate splicing.
In MR-D; loss of ability to activate splicing.
In MR-E; loss of ability to activate splicing.
In RS-A; loss of ability to activate splicing but retains splice site switching.
In RS-B; retains both splice activation and splice site switching activity.
In RS-C; loss of ability to activate splicing but retains splice site switching.
Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-93 and Ala-109.
Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-93 and Ala-97.
Predominantly localizes to cytoplasm and fails to modulate splicing of endogenous pre-mRNAs; when associated with Ala-97 and Ala-109.
Reduced nucleocytoplasmic shuttling; when associated with D-162.
Reduced nucleocytoplasmic shuttling; when associated with D-190.
Insulin growth factor-like family member 1
Forms mainly dimers. Forms mainly monomers; when associated with S-31.
Forms mainly monomers; when associated with S-48.
In CISS2; heterozygous compound with a nonsense mutation; unable to bind CNTFR alpha.
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 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.
EF-hand calcium-binding domain-containing protein 14
Nuclear pore complex-interacting protein family member B15
CKLF-like MARVEL transmembrane domain-containing protein 8
Abolishes binding to COTL1. Impairs interaction with DICER; when associated with A-14 and A-76.
Decreases arachidonate 5-lipoxygenase activity.
Decreases arachidonate 5-lipoxygenase activity. Increases leukotriene A4 synthase activity.
Does not affect arachidonate 5-lipoxygenase activity.
Does not affect arachidonate 5-lipoxygenase activity. Does not oxygenate arachidonate typical 15-lipoxygenase substrates such as dihomo-gamma-linolenic acid and N-arachidonyl glycine.
Enhances affinity for arachidonic acid. Impairs arachidonate 5-lipoxygenase activity. Induces arachidonate 15-lipoxygenase activity. Oxygenates typical arachidonate 15-lipoxygenase substrates such as dihomo-gamma-linolenic acid and N-arachidonyl glycine. Synthesizes lipoxin A4 when incubated with a stable 5-lipoxygenase.
Essential for stabilizing binding to COTL1
Impairs interaction with DICER1; when associated with A-14 and A-103.
Impairs interaction with DICER1; when associated with A-76 and A-103.
Increases arachidonate 5-lipoxygenase activity.
Increases arachidonate 5-lipoxygenase activity. Does not affect leukotriene A4 synthase activity.
Loss of (5S)-lipoxygenase activity. Loss of (5S)-lipoxygenase activity; when associated with W-360; I-425 and M-426. Exhibits a major (15S)-lipoxygenase activity;when associated with W-360; I-425 and M-426. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; I-425 and M-426. Abolishes the LTA4-synthase activity; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of linoleic acid to (13S)- and (9 S)-HODE; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; I-425 and M-426. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; I-425 and M-426. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; I-425 and M-426. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; I-425 and M-426. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; I-425 and M-426.
Loss of (5S)-lipoxygenase activity; when associated with I-425 and M-426. Loss of (5S)-lipoxygenase activity; when associated with I-425; M-426 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with I-425 and M-426. Exhibits a major (15S)-lipoxygenase activity; when associated with I-425; M-426 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of arachodonic acid to form mostly (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with I-425: M-426 and I-604. Abolishes the LTA4-synthase activity; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with I-425: M-426 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with I-425: M-426 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with I-425: M-426 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with I-425: M-426 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with I-425: M-426 and I-604.
Loss of (5S)-lipoxygenase activity; when associated with W-360 and I-425. Loss of (5S)-lipoxygenase activity; when associated with W-360; I-425 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360 and I-425. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360; I-425 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; I-425 and I-604. Abolishes the LTA4-synthase activity; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; I-425 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; I-425 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; I-425 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; I-425 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; I-425 and I-604.
Loss of (5S)-lipoxygenase activity; when associated with W-360 and M-426. Loss of (5S)-lipoxygenase activity; when associated with W-360; M-426 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360 and M-426. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360; M-426 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; M-426 and I-604. Abolishes the LTA4-synthase activity; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; M-426 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; M-426 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; M-426 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; M-426 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; M-426 and I-604.
Loss of phosphorylation site. Permits export from the nucleus.
Polyunsaturated fatty acid 5-lipoxygenase
MORF4 family-associated protein 1-like 1
Charge relay system; for autoendoproteolytic cleavage activity
Cleavage (non-hydrolytic); by autocatalysis
In LIBF; loss of autocatalytic processing; decreased protein abundance; decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization.
In LIBF; loss of autocatalytic processing; probably decreased phosphatidylserine decarboxylase activity; changed mitochondrion organization; patient-derived fibroblasts show fragmented mitochondrial morphology around the nucleus; decreased cell viability with increased CASP3 and CASP7 activation.
Necessary for localization to both lipid droplets and mitochondria
Phosphatidylserine decarboxylase alpha chain
Phosphatidylserine decarboxylase beta chain
Phosphatidylserine decarboxylase proenzyme, mitochondrial
Schiff-base intermediate with substrate; via pyruvic acid; for decarboxylase activity
Sperm acrosome membrane-associated protein 1
Phosphoribosyl pyrophosphate synthase-associated protein 1
Ribose-phosphate pyrophosphokinase N-terminal
Important for transcriptional repression activity
Synaptonemal complex central element protein 2
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.
Required for interaction with NRXN1 (via C-terminal tail)
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.
A disintegrin and metalloproteinase with thrombospondin motifs 16
Fibronectin type III domain-containing protein 3B
Chromodomain-helicase-DNA-binding protein 2
Found in a patient with progressive myoclonus epilepsy; unknown pathological significance.
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
At homozygosity reduces the risk for colorectal cancer in individuals with adequate folate status; decreased risk for adult acute leukemia; increased risk for NTDFS; increased risk for schizophrenia; thermolabile; decreased affinity for FAD cofactor; 50% reduced activity.
Decreased risk for adult acute leukemia; thermolabile; decreased activity.
In MTHFRD; decreased affinity for FAD cofactor.
In MTHFRD; loss of methylenetetrahydrofolate reductase activity.
In MTHFRD; reduced methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH.
In MTHFRD; reduced methylenetetrahydrofolate reductase activity; reduced affinity for NADPH.
In MTHFRD; reduces methylenetetrahydrofolate reductase activity; no effect on affinity for NADPH.
Methylenetetrahydrofolate reductase (NADPH)
No effect on S-adenosylmethionine-binding.
Reduces incorporation into the PeBoW complex and nucleolar localization and impairs maturation of 28S ribosomal RNA.
Required for 28S ribosomal RNA processing
Slightly impairs nucleolar localization.
In MANSB; complete loss of enzyme activity.
In MANSB; nearly complete loss of enzyme activity.
No effect on enzyme activity (in vitro).
No effect on enzyme activity (in vitro). Decreased protein stability.
No effect on enzyme activity (in vitro). No effect on protein stability.
Heterogeneous nuclear ribonucleoprotein Q
Putative cancer susceptibility gene HEPN1 protein
Abolishes enzymatic activity. Loss of the pro-apoptotic function.
Ubiquitin carboxyl-terminal hydrolase 17-like protein 24
Acquires D-mannose and D-allose transporter activity comparable to glucose and galactose.
Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and C-290.
Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with L-83 and C-290.
Has normal D-glucose and D-galactose transporter activity.
In GGM; about 90% reduction in activity.
In GGM; about 95% reduction in activity.
In GGM; impairs trafficking to the plasma membrane.
In GGM; impairs trafficking to the plasma membrane; decreases the sugar affinity.
In GGM; requires 2 nucleotide substitutions; about 90% reduction in activity.
Involved in sugar-binding/transport and inhibitor binding
Loss of D-galactose transporter activity. Has strict selectivity for D-glucose. Acquires D-mannose, D-fructose and L-sorbose transporter activity; when associated with A-287 and L-83.
Loss of D-glucose transporter activity. Has strict selectivity for D-galactose.
Slightly reduced D-glucose transporter activity.
Strong reduction in D-glucose transporter activity.
Dehydrogenase/reductase SDR family member 6
Probable JmjC domain-containing histone demethylation protein 2C
Low-density lipoprotein receptor class A domain-containing protein 2
Putative tripartite motif-containing protein 64B
Hydroxysteroid 11-beta-dehydrogenase 1-like protein
In isoform 2, isoform 5, isoform 6 and isoform 7.
Abolishes first cleavage by ESPL1, no effect on nuclear localization.
Abolishes second cleavage by ESPL1, no effect on nuclear localization.
Double-strand-break repair protein rad21 homolog
Found in a radiation-sensitive cancer patient.
In MGS; causes delayed food transit along the gut, when tested in zebrafish; may affect RUNX1 and APOB expression.
Loss of cleavage by caspase-3 or caspase-7.
No effect on cleavage by caspase-3 or caspase-7.
Abolishes interaction with UPF1; when associated with E-163.
Abolishes interaction with UPF1; when associated with E-66.
Nonsense-mediated mRNA decay factor SMG7
Telomerase activating protein Est1-like N-terminal
ABC-type organic anion transporter ABCA8
Affects localization at the plasma membrane; loss of cholesterol efflux to APOA1.
Loss of expression; loss of cholesterol efflux to APOA1.
In OI15; completely fails to activate the Wnt-regulated beta-catenin signaling cascade.
In OI15; reduced capacity to activate canonical Wnt signaling.
In OSTEOP; associated with susceptibility to early-onset osteoporosis; completely fails to activate the Wnt-regulated beta-catenin signaling cascade.
In OSTEOP; reduced capacity to activate canonical Wnt signaling.
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.
Leucine-rich repeat-containing protein 56
Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase 2
Only mildly affects mRNA cap binding and catalytic activity of the enzyme.
Strongly reduces mRNA cap binding and catalytic activity of the enzyme.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial
4-trimethylaminobutyraldehyde dehydrogenase
4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed
N-acetylserine; in 4-trimethylaminobutyraldehyde dehydrogenase, N-terminally processed
In MCOPS3; unknown pathological significance.
In mt1; reduced nuclear import; when associated with 56-A--A-58. In mt1.2; reduced nuclear import; when associated with 42-A-A-43 and 113-A--A-115.
In mt1; reduced nuclear import; when associated with 56-A--A-58. In mt1.2; reduced nuclear import; when associated with 56-A--A-58 and 113-A--A-115.
In mt2; reduced nuclear import. In mt1.2; reduced nuclear import; when associated with 42-A-A-43 and 56-A--A-58.
Loss of interaction with L3MBTL3. Loss of ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex. Loss of interaction with PHF20L1; when associated with R-117.
Loss of interaction with PHF20L1; when associated with R-42.
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 HYCX and MASA; also found in a patient with the diagnosis of L1 syndrome; also in a patient with hydrocephalus and Hirschsprung disease.
In HYCX and MASA; also in a patient with hydrocephalus and Hirschsprung disease.
In HYCX and MASA; associated with callosal agenesis; also found in a patient affected by hydrocephalus with Hirschsprung disease.
In HYCX 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 HYCX; 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 HYCX; partial loss of axon guidance and loss of proper synapse formation, when assayed in a heterologous system.
In HYCX; 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 HYCX; severe; loss of localization to the cell surface; retention in the endoplasmic reticulum; loss of axon guidance, when assayed in a heterologous system.
In HYCX; 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.
Tumor necrosis factor alpha-induced protein 8-like protein 2
Cation-transporting P-type ATPase N-terminal
Potassium-transporting ATPase alpha chain 1
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.
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.
Required for localization to nuclear speckles
SUMO interaction motifs (SIM); required for nuclear localization and kinase activity
Phospholipid phosphatase-related protein type 1
In PEHO; increased protein degradation; decreased protein abundance; does not affect localization to cytoplasm and nucleus.
Zinc finger HIT domain-containing protein 3
Loss of the cysteine S-conjugate N-acetyltransferase activity. No effect on protein expression.
No effect on the cysteine S-conjugate N-acetyltransferase activity.
R1 epitope (recognized by Chagas's antibodies)
R3 epitope (recognized by Chagas's antibodies)
Improved maturation and increased expression at the cell surface.
Loss of kinase activity and ability to activate JNK family.
Mitogen-activated protein kinase kinase kinase kinase 5
Abolishes dimerization. Does not affect cell membrane localization. Does not affect processing by BACE2. Abolishes dimerization; when associated with A-152.
Does not affect dimerization. Does not affect cell membrane localization. Abolishes dimerization; when associated with A-186.
Increased dimerization leading to hyperoligomerized. Abolishes processing by BACE2. Abolishes localization to the cell membrane.
Increases processing by BACE2. Decreases of protein abundance.
Loss of localization to the cell membrane. Abolishes processing by BACE2. Loss of localization to the cell membrane; when associated with I-76.
Loss of localization to the cell membrane. Abolishes processing by BACE2. Loss of localization to the cell membrane; when associated with I-93.
In CTRCT23; modeling suggests that this substitution would significantly reduce the intrinsic stability of the crystalline monomer.
In CTRCT23; the patient has cataract and bilateral microphthalmia; the mutation is predicted to disrupt the beta-sheet structure of the protein.
Histone-lysine N-methyltransferase SETD5
In MRD23; unknown pathological significance.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 111-D--L-116, 151-M--I-153, A-175, A-213 and 217-N--S-222.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 111-D--L-116, 151-M--I-153, A-175, L-184-D-185 and 217-N--S-222.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 111-D--L-116, 151-M--I-153, A-175, L-184-D-185 and A-213.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 111-D--L-116, 151-M--I-153, L-184-D-185, A-213 and 217-N--S-222.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 111-D--L-116, A-175, L-184-D-185, A-213 and 217-N--S-222.
Despite residues related to HVCN1 channel, does not show ion channel activity; when associated with 151-M--I-153, A-175, L-184-D-185, A-213 and 217-N--S-222.
In SIDBA4; unknown pathological significance.
Significant loss of interaction with FXN and ISCU. Significant increase in interaction with NFS1.
13-fold reduction in affinity for Ala-Pro-AFC; no effect on subcellular location.
Abolishes activity; no effect on subcellular location.
Loss of enzyme activity. Loss of dimerization.
Peptidase S9 prolyl oligopeptidase catalytic
Reduced dimerization and reduced enzyme activity.
von Willebrand factor A domain-containing protein 2
Lysosomal membrane ascorbate-dependent ferrireductase CYB561A3
NACHT and WD repeat domain-containing protein 2
Abolishes monoubiquitination by FANCL and UBE2T.
In FANCI; abolishes function in DNA repair.
In FANCI; benign variant; no effect on ubiquitination and DNA repair.
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.
Major facilitator superfamily domain-containing protein 12
Reduced localization to lysosomes and redirection to the cell membrane.
WAP four-disulfide core domain protein 10A
Loss of interaction with MAD2L1 and disruption of ability to overcome spindle checkpoint-dependent mitotic arrest; when associated with A-191.
Loss of interaction with MAD2L1 and disruption of ability to overcome spindle checkpoint-dependent mitotic arrest; when associated with A-83.
In LCCS1; allele Fin(Major); does not affect subcellular localization.
Mediates the shuttling between the nucleus and the cytoplasm
Variable number of tandem repeats (VNTR)
Heterogeneous nuclear ribonucleoprotein A/B
Sodium- and chloride-dependent betaine transporter
Zinc finger CCCH domain-containing protein 13
Essential for specifying alpha-elongation versus initiation step of the polyglutamylase activity
Phosphatidylinositol-glycan biosynthesis class X protein
Impairs DNA-binding and ability to repress PGC-1-alpha (PPARGC1A).
Found in autosomal dominant self-limited delayed puberty; unknown pathological significance.
Probable disease-associated variant found in autosomal dominant self-limited delayed puberty; the mutant protein is not secreted.
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
In MRD61; unknown pathological significance.
Mediator of RNA polymerase II transcription subunit 13
Impaired association with protein kinase PRKCG but not with SRC.
Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2
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.
Complete loss of binding to acetylated bovine serum albumin and chitin.
Complete loss of binding to acetylated bovine serum albumin and reduced binding to chitin; when associated with A-395.
Complete loss of binding to acetylated bovine serum albumin and reduced binding to chitin; when associated with N-395.
Fibrinogen C domain-containing protein 1
Significantly reduced binding to acetylated bovine serum albumin and loss of binding to chitin; when associated with S-405.
Significantly reduced binding to acetylated bovine serum albumin and loss of binding to chitin; when associated with S-431.
Slight reduction in binding to acetylated bovine serum albumin and no effect on binding to chitin.
In BDPLT15; disorganization of the actin and alpha-actinin 1 filaments.
In BDPLT15; the mutation dominantly affects the actin filament assembly likely resulting in abnormal cytoskeletal organization.
Insulin-like growth factor-binding protein-like 1
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.
Constitutively active. Results in increased rates of stress fiber dissolution and cell migration. No effect on ARHGAP30-binding.
Loss of GTP-binding and localization to focal adhesions. No effect on ARHGAP30-binding.
Loss of PAK3-binding; when associated with S-81 and A-83. No effect on ARHGAP30-binding.
Loss of binding to PAK3; when associated with A-83 and C-86.
Loss of binding to PAK3; when associated with S-81 and C-86.
Loss of subcellular location to plasma and intracellular membranes.
DNA-directed RNA polymerase I subunit RPA49
Mediator of RNA polymerase II transcription subunit 24
In CGL2; increases localization to nuclear envelope; no effect on its interaction with LDAF1; no rescue of aberrant lipid droplet formation in BSCL2-knockdown cells.
In SPG17 and HMN5C; also found in patients with hereditary motor and sensory neuropathy type 2; does not affect the function in lipid storage.
In SPG17 and HMN5C; does not affect protein subcellular location.
Loss of oligomerization and function in lipid droplet biogenesis; when associated with R-67; A-70; D-156; D-169 and A-175.
Loss of oligomerization and function in lipid droplet formation; when associated with A-70; A-151; D-156; D-169 and A-175.
Loss of oligomerization and function in lipid droplet formation; when associated with R-67; A-151; D-156; D-169 and A-175.
Loss of oligomerization and function in lipid droplet formation; when associated with R-67; A-70; A-151; D-156 and A-175.
Loss of oligomerization and function in lipid droplet formation; when associated with R-67; A-70; A-151; D-156 and D-169.
Loss of oligomerization and function in lipid droplet formation; when associated with R-67; A-70; A-151; D-169 and A-175.
Abolishes SNAPC5 binding in the absence of SNAPC1. Minimal effect on SNAPC5 binding in the presence of SNAPC1.
snRNA-activating protein complex subunit 4
In MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; does not affect PPP2R3A binding; decreases phosphatase activity of PPP2CA.
In MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; decreases phosphatase activity of PPP2CA.
In MRD36; reduces PPP2CA binding; reduces PPP2R5A binding; reduces PPP2R5C binding; does not affect PPP2R5D binding; reduces PPP2R2A binding; reduces PPP2R2B binding; reduces PPP2R3A binding; does not affect phosphatase activity of PPP2CA.
Polyoma small and medium T antigens Binding
Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
In MC3DN9; decreases protein abundance; reduces complex III formation; reduces complex III activity.
Loss of localization to the mitochondria.
Ubiquinol-cytochrome-c reductase complex assembly factor 3
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.
In SPGF53; unknown pathological significance; abolishes interaction with ACTL7A.
In SPGF53; unknown pathological significance; reduces interaction with ACTL7A.
B-cell antigen receptor complex-associated protein beta chain
In ALS22; displays significantly different distribution in terms of incorporation into microtubules.
In ALS22; displays significantly different distribution in terms of incorporation into microtubules; destabilizes the microtubule network.
In ALS22; displays significantly lower levels of dimer assembly.
Reduces catalytic activity by 1,000-fold to 2,500-fold.
Reduces catalytic activity by 25,000-fold to 100,000-fold.
Reduces catalytic activity by 300,000-fold to 500,000-fold.
Reduces catalytic activity by 5,000-fold to 15,000-fold.
FYVE, RhoGEF and PH domain-containing protein 6
Benign variant; no effect on mitochondrial potassium ion transmembrane transport; it fully rescues defective proton/potassium exchange in letm1-deficient yeast.
In CONDMIM; decreased function in mitochondrial potassium ion transmembrane transport; does not fully rescue defective proton/potassium exchange in letm1-deficient yeast.
In CONDMIM; homozygous patient cells show abnormal mitochondrial morphology and altered levels of components of the oxidative phosphorylation machinery; loss of function in mitochondrial potassium ion transmembrane transport; does not rescue defective proton/potassium exchange in letm1-deficient yeast.
In CONDMIM; homozygous patient cells show altered levels of components of the oxidative phosphorylation machinery; decreased function in mitochondrial potassium ion transmembrane transport; does not fully rescue defective proton/potassium exchange in letm1-deficient yeast.
In CONDMIM; unknown pathological significance.
In CONDMIM; unknown pathological significance; decreased function in mitochondrial potassium ion transmembrane transport; does not fully rescue defective proton/potassium exchange in letm1-deficient yeast.
Loss of ability to complement growth defects and morphologic defects of mitochondria in letm1-deficient yeast mutant; when associated with A-382 and A-383.
Loss of ability to complement growth defects and morphologic defects of mitochondria in letm1-deficient yeast mutant; when associated with A-382 and A-384.
Loss of ability to complement growth defects and morphologic defects of mitochondria in letm1-deficient yeast mutant; when associated with A-383 and A-384.
Loss of ability to complement morphologic defects of mitochondria in letm1-deficient yeast mutant. Slightly supports growth of letm1-deficient yeast mutant on minimal essential medium.
Mitochondrial proton/calcium exchanger protein
No effect on mitochondrial potassium ion transmembrane transport; it fully rescues defective proton/potassium exchange in letm1-deficient yeast.
Phosphomimetic mutant. Increased rate of calcium export from mitochondria.
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.
Negative regulator of microtubule-binding
Cytosolic Fe-S cluster assembly factor NUBP1
GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
In CDG1P; does not affect subcellular localization; results in the accumulation of under-glycosylated proteins.
Rare variant found in patients with X-linked intellectual disability; unknown pathological significance.
Found in a patient with severe intellectual disability, psychomotor delay, no speech, sleep disturbances, feeding problems, abnormal breething, deep-set eyes and short philtrum.
Increases homooligomer formation in presence or absence of magnesium.
Increases strongly homooligomer formation in presence of magnesium, but weakly in absence of magnesium.
Increases weakly homooligomer formation in presence of magnesium, but strongly in absence of magnesium.
Increases weakly homooligomer formation in presence or absence of magnesium.
Mitochondrial inner membrane protein OXA1L
Patatin-like phospholipase domain-containing protein 2
Reduces rate of lipid hydrolysis; does not affect the localization around the rim of the adiposomes.
Abolishes phosphorylation by CK2 in response to growth factor deprivation and subsequent ubiquitination and degradation.
Interaction with HSPA5 and localization to the endoplasmic reticulum
Breast cancer anti-estrogen resistance protein 1
Gamma-aminobutyric acid receptor subunit epsilon
Peptidyl-prolyl cis-trans isomerase A-like 4D
Disintegrin and metalloproteinase domain-containing protein 17
In ACRDYS1; impairs response of PKA to c-AMP.
In ACRDYS1; reduces PKA activity; decreases cAMP binding.
In ACRDYS1; reduces PKA activity; decreases cAMP binding; reduces protein degradation.
In CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit.
In CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; accelerates protein degradation.
In CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; reduces protein degradation.
cAMP-dependent protein kinase type I-alpha regulatory subunit
Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase
Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 4
Abolishes interaction with ATM-phosphorylated MDC1. Abolishes interaction with human herpesvirus 1 ICP0. Abolishes recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent.
Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes.
Impairs interaction with UBE2L6/UBCH8 and ability to mediate 'Lys-48'-linked ubiquitination E3 ligase activity, while it still catalyzes 'Lys-63'-linked ubiquitination and still interacts with UBE2N/UBC13.
Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization.
Abolishes methylcytosine dioxygenase activity.
In BEFAHRS; decreases methylcytosine dioxygenase activity.
In BEFAHRS; unknown pathological significance; no effect on methylcytosine dioxygenase activity.
Important for AKT1 activation and IL8 production
Does not inactivate the protein. gives rise to mechanically activated currents that inactivate more slowly than wild-type currents, suggesting it could shift the channel kinetics from phasic to tonic.
Found in Er(4-) blood group phenotype that is associated with hemolytic disease of the fetus and newborn.
Found in Er(5-) blood group phenotype that is associated with hemolytic disease of the fetus and newborn.
Found in Er(a-b+) and Er(a-b-) blood group phenotypes.
Found in Er(a-b+) blood group phenotype.
Found in Er(a-b-) blood group phenotype.
In DHS1; gives rise to mechanically activated currents that inactivate more slowly than wild-type currents.
In DHS1; increased cation transport in erythroid cells.
In LMPHM6; unknown pathological significance.
Piezo-type mechanosensitive ion channel component 1
In allele APOH*3W; loss of phosphatidylserine-binding.
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
In EVR6; severely decreased localization to the nucleus.
In EVR6; unknown pathological significance; does not affect localization to the nucleus.
In RP72; decreased localization to the nucleus.
In EDM5; bilateral hereditary microepiphyseal dysplasia.
In EDM5; retained and accumulates within the cell.
In isoform 2, isoform 4, isoform 5, isoform 6, isoform 8, isoform 9 and isoform 10.
In isoform 3, isoform 4, isoform 5, isoform 6, isoform 8, isoform 9 and isoform 10.
In isoform 3, isoform 5, isoform 7 and isoform 8.
LIM and calponin homology domains-containing protein 1
Actin-related protein 2/3 complex subunit 5-like protein
In RP92; unknown pathological significance; slightly decreased hexokinase activity.
Important for regulation of lamellipodia formation
Important for nuclear localization and chromatin binding
Acyl-coenzyme A synthetase ACSM5, mitochondrial
2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial
Reduces enzyme activity by 99%. Strongly reduced affinity for substrate and for NADP.
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.
Associated with susceptibility to schizoaffective disorder.
Impairs interaction with NDEL1; when associated with P-815.
Impairs interaction with NDEL1; when associated with P-822.
Necessary and sufficient for interaction with PCNT and localization at the centrosome
Required for localization to punctate cytoplasmic foci
Nearly abolishes phosphoceramide transfer.
Nearly abolishes phosphoceramide transfer. Induces autophagy in a dominant negative manner.
Slightly decreases phosphoceramide transfer.
Slightly reduces phosphoceramide transfer.
Strongly reduces phosphoceramide transfer.
In RP66; abolishes secretion; results in mis-folded insoluble complexes degraded via the ER-associated protein catabolic process.
Cytochrome c oxidase subunit 6A2, mitochondrial
In MC4DN18; reduced complex IV assembly; decreased COX6A2 protein stability.
Abolishes most of in vitro phosphatase activity.
No effect on in vitro phosphatase activity.
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform
Drastic reduction of virus infectibility, but conserved virus binding ability.
Loss of sodium-dependent phosphate transporter activity. Able to restore cell proliferation in SLC20A1-deficient HeLa cells to a level identical to that observed in their wild-type counterpart. No effect on its localization to the cell membrane.
Sodium-dependent phosphate transporter 1
Necessary for colocalization and binding with microtubules
Necessary for interaction with MARK2 and apicobasal microtubule bundle formation in polarized epithelial cells
Necessary for self-assembly, microtubule bundling activity and apicobasal microtubule organization
Ras association domain-containing protein 2
Abolishes oligomerization. Loss of enzyme activity.
Found in a patient with a severe multisystemic growth disorder and cerebellar atrophy; unknown pathological significance.
In SCAR28; decreased mitochondrial fusion.
LLGL scribble cell polarity complex component 2
Reduced N-glycosylation. Loss of N-glycosylation; when associated with A-353.
Reduced N-glycosylation. Loss of N-glycosylation; when associated with A-371.
Cadherin EGF LAG seven-pass G-type receptor 3
Found in a patient with epileptic encephalopathy; unknown pathological significance.
In a melanoma metastatic sample; somatic mutation.
In an ovarian undifferentiated carcinoma sample; somatic mutation.
Rare variant found in East Asian patients; decreases luminal apoptosis, cell aggregation and basolateral membrane localization in colorectal cancer cells.
FAST kinase domain-containing protein 3, mitochondrial
Tyrosine-protein phosphatase non-receptor type substrate 1
Proline, histidine and glycine-rich protein 1
DDB1- and CUL4-associated factor 8-like protein 1
Abolished glutathione import into mitochondria without affecting the levels of NAD.
Probable mitochondrial glutathione transporter SLC25A39
Endothelial differentiation-related factor 1
Loss of interaction with CALM and higher affinity for TBP. Same effect; when associated with D-65 and D-74.
Loss of interaction with CALM; when associated with D-40; D-58 and D-91.
Loss of interaction with CALM; when associated with D-40; D-91 and D-111.
Loss of interaction with CALM; when associated with D-58; D-91 and D-111.
No effect on CALM-binding. No effect; when associated with D-65.
No effect on CALM-binding. No effect; when associated with D-74.
Partial loss of interaction with CALM. Complete loss of interaction; when associated with D-40; D-58 and D-111.
Disrupts interaction with CEP290, no effect on interaction with BBS1, BBS2, BBS4, BBS8 and BBS9, abolishes ciliogenesis.
IQ calmodulin-binding motif-containing protein 1
Interaction with BBS1, BBS2, BBS4, BBS7, BBS8 and BBS9
Interaction with CEP290, BBS1, BBS2, BBS4, BBS5, BBS7, BBS8 and BBS9
Abolishes the ability of the Integrator complex to process U1 and U2 snRNA genes.
Abolishes kinase activity, ability to activate the MAPK8/JNK cascade and cleavage by caspase-3 (CASP3).
Abolishes phosphorylation by ATM; when associated with A-643 and A-785.
Abolishes phosphorylation by ATM; when associated with A-643 and A-990.
Abolishes phosphorylation by ATM; when associated with A-785 and A-990.
Does not abolish cleavage by caspase-3 (CASP3).
In DDIB; affects neuron maturation and migration.
In DDIB; unknown pathological significance.
Loss of serine/threonine-protein kinase activity.
Pregnancy-specific beta-1-glycoprotein 9
In a patient with gray platelet syndrome.
Abolished activation due to the presence of the N-terminal disordered prodomain. Abolished processing and subsequent activation; when associated with A-179 and A-193.
Abolished phosphorylation, leading to caspase-6 activation.
Abolished processing and subsequent activation; when associated with A-23 and A-179.
Abolished processing and subsequent activation; when associated with A-23 and A-193.
Catalytically inactive active-site mutant.
Decreased ability to hydrolyze substrates.
Phospho-mimetic mutant; loss of self-activation.
Phospho-mimetic mutant; prevents caspase-6 autoactivation.
Reduced palmitoylation, leading to increased cysteine protease activity.
Cilia- and flagella-associated protein 58
In SPGF49; results in loss of mutant protein; results in axonemal abnormalities.
In SPGF49; unknown pathological significance.
Decreased acetylation and increased de novo lipid synthesis; when associated with R,Q-540 and R,Q-546. Abolished ubiquitination by the BCR(KLHL25) complex; when associated with R-540 and R-546.
Decreased acetylation and increased de novo lipid synthesis; when associated with R,Q-540 and R,Q-554. Abolished ubiquitination by the BCR(KLHL25) complex; when associated with R-540 and R-554.
Decreased acetylation and increased de novo lipid synthesis; when associated with R,Q-546 and R,Q-554. Abolished ubiquitination by the BCR(KLHL25)complex; when associated with R-546 and R-554.
Phosphoserine; by PKA and PKB/AKT1 or PKB/AKT2
About 90% loss of phosphorylation by DYRK1A; when associated with A-368.
About 90% loss of phosphorylation by DYRK1A; when associated with A-403.
Does not affect recruitment to DSBs nor ability to inhibit DSBs repair.
Does not affect ubiquitin-binding but abolishes recruitment to DSBs.
Abolishes enzyme activity and ability to bind tRNA.
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)
NAD(P)H pyrophosphatase NUDT13, mitochondrial
Calcium-activated potassium channel BK alpha subunit
In DEE14; unknown pathological significance.
In DEE14; variant homologue in rat has increased channel activity upon positive potentials.
Actin-related protein 2/3 complex subunit 1A
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.
T-cell activation Rho GTPase-activating protein
In NTD; uncertain pathological significance.
In NTD; uncertain pathological significance; loss of function; no effect on mitochondrial localization.
In RREI; decreases succinate dehydrogenase activity and glycerol-3-phosphate dehydrogenase activity.
In RREI; results in impaired FAD transporter activity and lower FAD, FMN and riboflavin mitochondrial levels, when expressed in murine skeletal muscle cells; motor function impairment shown by a mouse knockin model of the mutation.
In RREI; results in reduced transcript and protein levels while retaining normal FAD transporter activity, when expressed in murine skeletal muscle cells.
Abolishes APC/C-mediated degradation; when associated with A-992 and A-1000.
Abolishes APC/C-mediated degradation; when associated with A-992 and A-995.
Abolishes APC/C-mediated degradation; when associated with A-995 and A-1000.
Abolishes interaction with NEDD4 and impairs ubiquitination.
Abolishes interaction with NEDD4 and impairs ubiquitination. Promotes nuclear translocation of ERBB4 intracellular domain E4ICD1.
Abolishes interaction with WWP1; when associated with F-1056.
Abolishes interaction with WWP1; when associated with F-1301.
Abolishes kinase activity. Abolishes phosphorylation, proteolytic processing and nuclear localization.
Abolishes nuclear localization of the ERBB4 intracellular domain.
Abolishes proteolytic processing and nuclear localization.
In ALS19; reduces autophosphorylation upon NRG1 stimulation.
In isoform JM-ACYT-2 and isoform JM-BCYT-2.
In isoform JM-BCYT-1 and isoform JM-BCYT-2.
No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1035. Loss of interaction with YAP1 and stimulation of transcription.
No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1301.
Found in patients with amyotrophic lateral sclerosis.
N-linked (GlcNAc...) (keratan sulfate) asparagine
Neuroblastoma breakpoint family member 10
Neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adapter 1
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.
Impaired dimerization; when associated with E-100.
Impaired dimerization; when associated with E-173.
Solute carrier family 2, facilitated glucose transporter member 14
Calcium-activated potassium channel subunit beta-3
Natural cytotoxicity triggering receptor 2
In NEDBAS; unknown pathological significance.
Abolished ability to bind N6-methyladenosine (m6A)-containing RNAs.
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.
Decreased activity with inositol 1,4,5-trisphosphate. Increased phosphorylation of inositol 1,3,4,5-tetrakisphosphate.
Decreased activity with inositol 1,4,5-trisphosphate. No effect on phosphorylation of inositol 1,3,4,5-tetrakisphosphate.
Loss of kinase activity and ability to execute necroptosis; when associated with A-146.
Loss of kinase activity and ability to execute necroptosis; when associated with N-144.
No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 2-A--P-69 DEL and 279-S--V-365 DEL.
No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 2-A--P-69 DEL and 366-G--S-373 DEL.
No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 279-S--V-365 DEL and 366-G--S-373.
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.
Does not reduce H2A stability. Interacts more strongly with monoubiquitinated H2A than with nonubiquitinated H2A. Its nuclear localization to chromatin is enhanced.
Does not reduce monoubiquitinated H2A and H2B stability. Interaction with monoubiquitinated H2A is strongly inhibited.
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 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.
Protein phosphatase 1 regulatory subunit 3F
Loss of phosphorylation; when associated with A-46.
Loss of phosphorylation; when associated with A-47.
Loss of phosphorylation; when associated with A-52.
Loss of phosphorylation; when associated with A-54.
MAP kinase docking motif; essential for its phosphorylation
Reduced interaction with MEN1; when associated with E-46.
Reduced interaction with MEN1; when associated with E-47.
Changed function; unable to rescue the corresponding loss of function zebrafish mutant which displays a cilium function alteration phenotype.
Does not affect fold stability, as assessed by circular dichroism thermal denaturation melting curves and by NMR spectroscopy. Affects interaction with PKD1.
Impairs interaction with PACS1; when associated with A-121 and A-123.
Impairs interaction with PACS1; when associated with A-121 and A-126.
Impairs interaction with PACS1; when associated with A-123 and A-126.
In NPHP1; associated with Cogan-type congenital ocular motor apraxia.
Abrogates regulation of alternative splice site selection; when associated with A-37; A-113 and A-115.
Abrogates regulation of alternative splice site selection; when associated with A-37; A-39 and A-113.
Abrogates regulation of alternative splice site selection; when associated with A-37; A-39 and A-115.
Abrogates regulation of alternative splice site selection; when associated with A-39; A-113 and A-115.
Inhibits IRES-mediated mRNA translation. Does not inhibit interaction with EIF4A1. Inhibits localization in cytoplasm and cytoplasmic granules upon cell muscle differentiation. Inhibits negative regulation of translation involved in gene silencing by miRNA.
Abolishes interaction with EIF4A3, EJC formation and localization in nucleus speckles.
Necessary for RNA-binding, interaction with MAGOH and localization in nucleus speckles
Necessary for localization in cytoplasmic stress granules
In ASD9 and TOF; loss of transcriptional activity.
In AVSD5; increased transcriptional activity.
In CTHM; persistent truncus arteriosus; loss of transcriptional activity.
In PACHD; loss of transcriptional activity.
In TOF; uncertain pathological significance; does not affect transcriptional activity.
Probable disease-associated variant found in patients with atrial fibrillation; gain of function; no effect on subcellular localization.
Probable disease-associated variant found in patients with atrial fibrillation; significant loss of transcriptional activator activity.
Increase in autophosphorylation but not kinase activity.
Loss of CDC42 binding; when associated with A-1579.
Loss of CDC42 binding; when associated with A-1582.
Prevents cleavage by CASP3, impairs the increase of its kinase activity and impairs extrusion apical actin ring assembly.
Serine/threonine-protein kinase MRCK alpha
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 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.
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.
Ankyrin repeat domain-containing protein 22
Class E basic helix-loop-helix protein 23
Decreases binding to MTRR; when associated with E-963.
Decreases binding to MTRR; when associated with N-1071.
Abolishes microtubules-binding when missing
In SLSN9; does not localize to the ciliary tip.
In SLSN9; results in altered folding of the N-terminus; does not affect interaction with IFT20; loss of interaction with MAP4.
In SLSN9; results in altered folding of the N-terminus; does not localize to the ciliary tip and transition zone; does not affect interaction with IFT20; loss of interaction with MAP4.
Interchain (with C-563 in SUN2); alternate
Abolishes phosphorylation. Abolishes interaction with DLC1 and p85.
Constitutive interaction with p85 and interaction with DLC1 after EGF stimulation.
Significantly reduced interaction with PEAK1; when associated with F-1173 and F-1206.
Significantly reduced interaction with PEAK1; when associated with F-1173 and F-1256.
Significantly reduced interaction with PEAK1; when associated with F-1206 and F-1256.
Drastically reduced targeting to the Golgi apparatus, small decrease in RAB6A-binding.
Loss of RAB6A-binding and of targeting to the Golgi apparatus.
No effect on RAB6A-binding, nor on targeting to the Golgi apparatus.
No effect on subcellular localization at the Golgi apparatus, small decrease in RAB6A-binding.
No effect on subcellular localization at the Golgi apparatus.
Abolishes inhibition of caspases and anti-apoptotic activity.
Abolishes inhibition of caspases, SMAC binding and anti-apoptotic activity.
Baculoviral IAP repeat-containing protein 7
Baculoviral IAP repeat-containing protein 7 30kDa subunit
No change in SMAC interaction and anti-apoptotic activity.
Found in a patient with combined respiratory complex deficiencies, muscle weakness and hearing loss; unknown pathological significance.
In colorectal adenocarcinomas cell line; loss of ribonucleotide reductase activity.
Ribonucleoside-diphosphate reductase subunit M2 B
HLA class II histocompatibility antigen, DQ beta 1 chain
In allele DQB1*02:01 and allele DQB1*02:02.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04 and allele DQB1*02:05.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04 and allele DQB1*02:05; requires 2 nucleotide substitutions.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05 and allele DQB1*06:06.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:02, allele DQB1*03:03, allele DQB1*03:05, allele DQB1*03:06, allele DQB1*03:07, allele DQB1*03:08, allele DQB1*03:10, allele DQB1*03:11, allele DQB1*03:12, allele DQB1*03:14, allele DQB1*03:15, allele DQB1*03:17, allele DQB1*03:18, allele DQB1*03:20, allele DQB1*03:23, allele DQB1*03:25, allele DQB1*03:26, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:06, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:02, allele DQB1*03:03, allele DQB1*03:05, allele DQB1*03:06, allele DQB1*03:07, allele DQB1*03:08, allele DQB1*03:11, allele DQB1*03:15, allele DQB1*03:17, allele DQB1*03:18, allele DQB1*03:20, allele DQB1*03:23, allele DQB1*03:25, allele DQB1*03:26, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:02, allele DQB1*03:03, allele DQB1*03:06, allele DQB1*03:07, allele DQB1*03:08, allele DQB1*03:11, allele DQB1*03:12, allele DQB1*03:15, allele DQB1*03:18, allele DQB1*03:20, allele DQB1*03:23, allele DQB1*03:25, allele DQB1*03:26, allele DQB1*04:03, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:06, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39; requires 2 nucleotide substitutions.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:06, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05 and allele DQB1*06:06.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:06, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:04, allele DQB1*06:01 and allele DQB1*06:35.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*06:01, allele DQB1*06:28 and allele DQB1*06:35.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:03, allele DQB1*02:04, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05 and allele DQB1*06:06.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:04, allele DQB1*02:05, allele DQB1*03:02, allele DQB1*03:04, allele DQB1*03:05, allele DQB1*03:07, allele DQB1*03:08, allele DQB1*03:11, allele DQB1*03:14, allele DQB1*03:18 and allele DQB1*06:29.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:04, allele DQB1*03:02, allele DQB1*03:03, allele DQB1*03:05, allele DQB1*03:23, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*02:01, allele DQB1*02:02, allele DQB1*02:04, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*03:02, allele DQB1*03:03, allele DQB1*03:05, allele DQB1*03:19, allele DQB1*03:25, allele DQB1*04:01 and allele DQB1*04:02.
In allele DQB1*03:02, allele DQB1*03:03, allele DQB1*04:01, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*06:02 and allele DQB1*06:12.
In allele DQB1*03:05, allele DQB1*03:17, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05 and allele DQB1*06:23; requires 2 nucleotide substitutions.
In allele DQB1*03:06, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03 and allele DQB1*05:04; requires 2 nucleotide substitutions.
In allele DQB1*03:06, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04 and allele DQB1*05:05; requires 2 nucleotide substitutions.
In allele DQB1*03:08, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:08, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31 and allele DQB1*06:33.
In allele DQB1*03:11, allele DQB1*03:26, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:05, allele DQB1*06:20 and allele DQB1*06:31.
In allele DQB1*03:22, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:34, allele DQB1*06:36 and allele DQB1*06:38.
In allele DQB1*03:23, allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:06, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:35, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*03:23, allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:06, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:20, allele DQB1*06:22, allele DQB1*06:21, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*03:25, allele DQB1*04:01, allele DQB1*04:02 and allele DQB1*04:03.
In allele DQB1*04:01, allele DQB1*04:02, allele DQB1*04:03, allele DQB1*06:02, allele DQB1*06:10, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:29, allele DQB1*06:33 and allele DQB1*06:37.
In allele DQB1*05:01 and allele DQB1*05:02.
In allele DQB1*05:01, allele DQB1*05:02 and allele DQB1*05:03.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:35, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:35, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38, allele DQB1*06:39.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:35, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39; requires 2 nucleotide substitutions.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:12, allele DQB1*06:14, allele DQB1*06:15, allele DQB1*06:16, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:34, allele DQB1*06:35, allele DQB1*06:36, allele DQB1*06:37, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:08, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:16, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:35 and allele DQB1*06:37.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:07, allele DQB1*06:08, allele DQB1*06:14, allele DQB1*06:17, allele DQB1*06:21, allele DQB1*06:25, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:15, allele DQB1*06:17, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:25, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39; requires 2 nucleotide substitutions.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*05:05, allele DQB1*06:17, allele DQB1*06:24 and allele DQB1*06:30.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12 and allele DQB1*06:36.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*05:03, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12 and allele DQB1*06:36.
In allele DQB1*05:01, allele DQB1*05:02, allele DQB1*06:02 and allele DQB1*06:12.
In allele DQB1*05:01, allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:06, allele DQB1*06:08, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:13, allele DQB1*06:17, allele DQB1*06:18, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:27, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*05:02, allele DQB1*05:04, allele DQB1*05:05, allele DQB1*06:10 and allele DQB1*06:25; requires 2 nucleotide substitutions.
In allele DQB1*06:01 and allele DQB1*06:35.
In allele DQB1*06:01 and allele DQB1*06:35; requires 2 nucleotide substitutions.
In allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:04, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
In allele DQB1*06:01, allele DQB1*06:02, allele DQB1*06:03, allele DQB1*06:08, allele DQB1*06:10, allele DQB1*06:11, allele DQB1*06:13, allele DQB1*06:14, allele DQB1*06:16, allele DQB1*06:18, allele DQB1*06:19, allele DQB1*06:20, allele DQB1*06:23, allele DQB1*06:24, allele DQB1*06:27, allele DQB1*06:28, allele DQB1*06:29, allele DQB1*06:30, allele DQB1*06:31, allele DQB1*06:32, allele DQB1*06:33, allele DQB1*06:35 and allele DQB1*06:37.
In allele DQB1*06:02 and allele DQB1*06:12.
In allele DQB1*06:04, allele DQB1*06:05, allele DQB1*06:07, allele DQB1*06:09, allele DQB1*06:12, allele DQB1*06:15, allele DQB1*06:17, allele DQB1*06:21, allele DQB1*06:22, allele DQB1*06:25, allele DQB1*06:34, allele DQB1*06:36, allele DQB1*06:38 and allele DQB1*06:39.
17-beta-hydroxysteroid dehydrogenase type 3
Almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.
Has 70% of wild-type testosterone 17-beta-dehydrogenase (NADP(+)) activity.
In MPH; Cambridge-1; complete loss of activity.
In MPH; Cambridge-2; affects NADPH cofactor binding.
In MPH; Gaza; ; almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.
In MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.
In MPH; almost complete loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity; no effect on protein abundance; no effect on endoplasmic reticulum location.
In MPH; loss of testosterone 17-beta-dehydrogenase (NADP(+)) activity.
Does not affect localization to Golgi apparatus.
In MLIIIC; decreased localization to Golgi apparatus.
In MLIIIC; loss of localization to Golgi apparatus.
N-acetylglucosamine-1-phosphotransferase subunit gamma
Rare variant; found in individuals suffering from stuttering; unknown pathological significance.
Decreases lysosomal localization. Loss of lysosomal localization; when associated with A-100.
Decreases lysosomal localization. Loss of lysosomal localization; when associated with A-57.
Decreases lysosomal localization. Loss of lysosomal localization; when assosiated with R-17. Loss of lysosomal localization; when assosiated with K-45 and K-49. Does not affect peptide transport activity; when assosiated with K-45 and K-49. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with R-17.
Decreases lysosomal localization; when associated with N-45.
Decreases lysosomal localization; when associated with N-49.
Important for the second trafficking step from the Golgi to the endosomal and lysosomal compartments
Intramolecular salt bridge with Arg-57. Essential for the release from the ER
Intramolecular salt bridge with Asp-17. Essential for the release from the ER
Loss of lysosomal localization. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect dimerization. Does not affect peptide transport activity. Decreases interaction with YIF1B.
Loss of lysosomal localization. Does not affect lysosomal localization; when associated with D-57. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with D-57. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with D-100.
Loss of lysosomal localization. Does not affect lysosomal localization; when associated with R-17. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with R-17.
Loss of lysosomal localization; when assosiated with K-45. Loss of lysosomal localization; when assosiated with K-45 and D-100. Does not affect peptide transport activity; when assosiated with K-45 and D-100.
Loss of lysosomal localization; when assosiated with K-49. Loss of lysosomal localization; when assosiated with K-49 and D-100. Does not affect peptide transport activity; when assosiated with K-49 and D-100.
Loss of peptide transport activity; whena ssociated with A-545.
Loss of peptide transport activity; whena ssociated with A-699.
In DEE2; affect activity; causes mislocalization of the protein in the cytoplasm.
In DEE2; affect activity; does not affect the cellular distribution of the protein.
In DEE2; causes mislocalization of the protein in the cytoplasm.
In DEE2; unknown pathological significance.
Probable disease-associated variant found in a patient with infatile spasms.
Phosphothreonine; by ROCK2 and PKC/PRKCI
Pleckstrin homology domain-containing family G member 7
Decreased reactivity with O6-benzylguanine.
Decreases activity towards methylated DNA over 1000-fold. No effect on reactivity with O6-benzylguanine.
Decreases activity towards methylated DNA over 1000-fold. Slightly reduced reactivity with O6-benzylguanine.
Loss of DNA repair activity. Slightly reduced reactivity with O6-benzylguanine.
Methylated-DNA--protein-cysteine methyltransferase
Methylated-DNA-[protein]-cysteine S-methyltransferase DNA binding
Methylguanine DNA methyltransferase ribonuclease-like
Reduced DNA repair activity. Decreased reactivity with O6-benzylguanine.
3 X 9 AA tandem repeats of P-K-C-P-[EQ]-P-C-P-P
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.
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.
Required for ubiquitination and degradation
Cation channel sperm-associated protein 2
Potassium voltage-gated channel subfamily E member 4
Nuclear factor of activated T-cells, cytoplasmic 3
ATP synthase subunit delta, mitochondrial
In MC5DN5; no effect on protein abundance; decreased mitochondrial proton-transporting ATP synthase complex assembly; decreased aerobic respiration in patient cells homozygous for the mutation; partial loss of function confirmed by complementation assays.
In OZEMA3; loss of interaction with ZP2.
Processed zona pellucida sperm-binding protein 3
Pyrrolidone carboxylic acid; in short chain
In MCPH17; impairs kinase activity; exhibits abnormal mitotic cytokinesis; exhibits multipolar spindles; increases the neurons apoptotic process.
Found in a patient with early-onset epithelial ovarian tumor; alters the ratio of secreted activins and ihibins; uncertain pathological significance.
Found in a patient with early-onset epithelial ovarian tumor; uncertain pathological significance.
Found in patients with atrial fibrillation; unknown pathological significance; loss of its inhibitory effects on KCNQ1.
Found in patients with ventricular fibrillation; unknown pathological significance; loss of its inhibitory effects on KCNQ1.
Potassium voltage-gated channel subfamily E regulatory beta subunit 5
Phosphothreonine; by MAP2K3, MAP2K4 and MAP2K6
Phosphotyrosine; by MAP2K3, MAP2K4 and MAP2K6
Actin filament-associated protein 1-like 2
Progestin and adipoQ receptor family member 3
Abolished catalytic activity; when assiociated with Ile-54-Thr, restores wild-type transcriptional activity.
Increased transcriptional activity; when associated with Ala-61-Val, restores wild-type transcriptional activity.
Paired-like homeodomain transcription factor LEUTX
Required for binding to the 5'-TAATCC-3' sequence
Loss of E3 ubiquitin-protein ligase activity; when associated with A-61.
Loss of E3 ubiquitin-protein ligase activity; when associated with A-64.
Loss of antiviral activity; able to form dimers but not higher-order multimers.
Loss of antiviral activity; able to form dimers but not higher-order multimers; when associated with A-91.
Loss of antiviral activity; able to form dimers but not higher-order multimers; when associated with A-96.
(Microbial infection) ADP-riboxanated arginine
Abolished ADP-riboxanation by C.violaceum CopC.
Inhibits tyrosine phosphorylation. Reduces caspase-9 subunit p35 formation in response to genotoxic stress. Attenuates ABL1/c-Abl-mediated caspase-3 activation, DNA fragmentation and UV irradiation-induced apoptosis.
ATP synthase subunit ATP5MJ, mitochondrial
In HYC5; associated with disease susceptibility.
MarR-like, BRCT and chromo domains module
Activating mutation resulting in 1.5-fold increase in basal cAMP production compared to the wild-type receptor.
Associated with longer menstrual cycles.
In ODG1; FSH binding is barely detectable; impaired targeting to the cell membrane; adenylate cyclase stimulation by FSH is 4 +-2% residual activity.
In ODG1; alters signal transduction of the receptor; adenylate cyclase stimulation by FSH is 24 +-4% residual activity.
In ODG1; binds FSH with a similar affinity than the wild-type receptor; adenylate cyclase stimulation by FSH is 12 +-3% residual activity.
In ODG1; impairs cell surface expression.
In ODG1; totally impairs adenylate cyclase stimulation in vitro; alters the cell surface targeting of the receptor which remains trapped intracellularly.
In ODG1; very frequent in the Finnish population.
In OHSS; decreases cell surface expression; no effect on hormone binding; increases levels of internalized hormone receptor complex; cAMP levels are similar to basal levels even at high doses of FSH stimulation indicating reduced signaling.
In OHSS; displays increase in affinity and sensitivity toward hCG and does not show any constitutive activity nor promiscuous activation by TSH.
In OHSS; displays promiscuous activation by both hCG and TSH together with detectable constitutive activity.
In OHSS; increase of receptor sensitivity to both hCG and TSH together with an increase in basal activity.
In OHSS; increases cell surface expression; no effect on hormone binding; increases signaling activity.
In OHSS; inhibits activation of PI3K/AKT signaling pathway; reduces cAMP production; no effect on ERK1/2 signaling pathway activation.
In ovarian sex cord tumor; loss of function.
No change in intracellular cAMP accumulation.
Reduces intracellular cAMP accumulation.
Breakpoint for translocation to form RBM15-MRTFA
In IMD66; probable loss-of-function; patient's dendritic cells are morphologically distinct from control dendritic cells and show reduced spreading on fibronectin-coated coverslips, a marked reduction in total F-actin staining and a complete absence of podosomes, a similar phenotype to that of THP1 cells in which MRTFA was silenced.
Myocardin-related transcription factor A
Cytochrome c oxidase assembly factor 4 homolog, mitochondrial
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.
In ARMD6; associated with disease susceptibility; increased transactivation and DNA-binding activity.
In CORD11; unknown pathological significance; decreased interaction with CRX and increased transactivation activity.
In CORD11; unknown pathological significance; decreased interaction with CRX and transactivation activity.
In RP95; unknown pathological significance.
Retina and anterior neural fold homeobox protein 2
Uveal autoantigen with coiled-coil domains and ankyrin repeats
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
No mitotic repression of transcriptional activity of the reconstituted TFIIH complex.
Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex.
Retains some of the calcium channel activity.
H/ACA ribonucleoprotein complex subunit 2
In LIS6; causes reduced interaction with KATNA1 and NDEL1.
Katanin p80 WD40 repeat-containing subunit B1
Loss of Golgi colocalization and gain of microtubule colocalization; when associated with C-10 and C-11.
Loss of Golgi colocalization and gain of microtubule colocalization; when associated with C-5 and C-10.
Loss of Golgi colocalization and gain of microtubule colocalization; when associated with C-5 and C-11.
Marked decrease in phosphorylation. Increased PPP1C-binding. No effect on HNRPK-binding.
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit A
Membrane-spanning 4-domains subfamily A member 7
Immunoglobulin-like domain-containing receptor 2
In PRAAS4; unknown pathological significance.
Associated with MODY11; reduces the enhancing effect of BLK on insulin secretion; reduces the inducing effect of BLK on the expression of PDX1 and NKX6-1; found as somatic mutation in a colorectal adenocarcinoma sample.
Glucosamine 6-phosphate N-acetyltransferase
Reduces affinity for glucosamine-6-phosphate 6-fold.
60% reduced ability to interact with the 3A protein of enterovirus D68.
75% reduced ability to interact with the 3A protein of enterovirus D68.
80% reduced ability to interact with the 3A protein of enterovirus D68.
95% reduced ability to interact with the 3A protein of enterovirus D68.
Almost complete loss of Golgi loalization.
Almost complete loss of PI4KB- and TBC1D22B-binding.
Complete loss of interaction with PI4KB.
Differential effect on PI4KB- and TBC1D22B-binding, with PI4KB-binding being much more affected than TBC1D22B-binding.
Differential loss of PI4KB- and TBC1D22B-binding, with PI4KB-binding being much more affected than TBC1D22B-binding.
Golgi resident protein GCP60, N-terminally processed
Loss of PI4KB-, TBC1D22A- and TBC1D22B-binding.
N-acetylalanine; in Golgi resident protein GCP60, N-terminally processed
No effect on PI4KB- and TBC1D22B-binding.
No effect on PI4KB-, TBC1D22A- and TBC1D22B-binding.
No effect on interaction with PI4KB but loss of interaction with Kobuviral (Aichi) 3A protein. Loss of ability to sensitize PI4KB activation by Kobuviral (Aichi) 3A protein.
Partial loss of PI4KB- and TBC1D22B-binding.
Q domain; Interaction with PI4KB, TBC1D22A and TBC1D22B
In CMYP19; loss-of-function variant resulting in a reduced muscle stem cell pool; the protein is not detected in patient muscle.
Sufficient to mediate interaction with PAXBP1
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
von Willebrand factor C and EGF domain-containing protein
Endogenous retroviral envelope protein HEMO
Endogenous retroviral envelope protein HEMO, secreted form
Introduction of a furin cleavage site, promoting proteolytic cleavage of the protein by furin and release in the extracellular medium.
Promotes release in the extracellular medium.
Disheveled-associated activator of morphogenesis 1
Abolishes p53 ubiquitination and degradation but not that of JUN; when associated with A-136.
Abolishes p53 ubiquitination and degradation but not that of JUN; when associated with A-139.
Loss of MTA1 ubiquitination and degradation; when associated with S-156.
Loss of MTA1 ubiquitination and degradation; when associated with S-159.
Loss of SFN and MTA1 ubiquitination and degradation; when associated with S-136. Loss of stabilization by COPS6; when associated with S-136.
Loss of SFN and MTA1 ubiquitination and degradation; when associated with S-139. Loss of stabilization by COPS6; when associated with S-139.
17 X 5 AA repeats of C-C-[RQVSGE]-[SPTQ]-[TASP]
Allele ALAD*2; ALAD*2 heterozygous or homozygous carriers have significantly higher blood lead levels than ALAD*1 homozygotes when exposed to environmental lead; fully active octamer.
In AHEPP; about 95% octamer; about 40% residual activity.
In AHEPP; mainly octamer; reduced activity.
In AHEPP; mixture of about 14% hexamer and 86% octamer; about 20% enzyme residual activity.
In AHEPP; mixture of about 50% hexamer and 50% octamer; about 10% residual activity.
In AHEPP; mixture of about 80% hexamer and 20% octamer; about 4% residual activity.
In an asymptomatic patient with ALAD deficiency; also found in a hereditary coproporphyria patient carrying the R-279 mutation in CPOX; hexamer with almost no residual activity.
No effect on catalytic activity; when associated with A-131.
No effect on catalytic activity; when associated with A-223.
Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-124.
Reduces enzyme activity about 1000000-fold; when associated with A-122 and A-132.
Reduces enzyme activity about 1000000-fold; when associated with A-124 and A-132.
Required for localization in mitochondria
Required for localization in sarcoplasmic reticulum
N-linked (GlcNAc...) asparagine; atypical; partial
Remains sulfated. Not sulfated and reduced rolling of Jurkat T-cells by more than 50%; when associated with F-118. The rolling of Jurkat T-cells is reduced by more than 80%; when associated with F-118 and A-124.
Remains sulfated. Not sulfated and reduced rolling of Jurkat T-cells by more than 50%; when associated with F-97. The rolling of Jurkat T-cells is reduced by more than 80%; when associated with F-97 and A-124.
26S proteasome non-ATPase regulatory subunit 14
Abolishes ubiquitin thioesterase activity, leading to prevent maintenance of JMJD2A/KDM4A on chromatin.
Ral guanine nucleotide dissociation stimulator-like 3
Branched-chain-amino-acid aminotransferase, mitochondrial
Golgin subfamily A member 6-like protein 10
DNA-directed RNA polymerase II subunit RPB2
DNA-directed RNA polymerase subunit 2 hybrid-binding
Coiled-coil domain-containing protein 43
Mediator of RNA polymerase II transcription subunit 30
Reduces enzyme activity. Abolishes enzyme activity; when associated with A-160.
Strongly reduces enzyme activity. Abolishes enzyme activity; when associated with A-183.
In ECYT3; decreased interaction with HIF1A and EPAS1 and decreased enzyme activity.
In ECYT3; marked decrease in enzyme activity.
Increased protection from polycythemia at high altitude; when associated with E-4.
Increased protection from polycythemia at high altitude; when associated with S-127.
Reduced C-terminal ODD domain (CODD) hxdroxylation of HIF1A.
Reduced C-terminal ODD domain (CODD) hydroxylation of HIF1A.
Impairs interchain disulfide bridge formation.
Increases formation of a highly stable disulfide-bonded PDIA2 dimer.
Lowers pKa of C-terminal Cys of first active site
Lowers pKa of C-terminal Cys of second active site
No effect on interchain disulfide bridge formation.
Cell cycle checkpoint control protein RAD9B
Decreases heparin-binding activity. Impairs heparin-binding activity and leukocyte transendothelial migration; when associated with A-94 and A-95.
Impairs heparin-binding activity and leukocyte transendothelial migration; when associated with A-91 and A-94.
Impairs heparin-binding activity and leukocyte transendothelial migration; when associated with A-91 and A-95.
Zinc finger protein with KRAB and SCAN domains 3
Nuclear pore complex-interacting protein family member A1
35 kDa inter-alpha-trypsin inhibitor heavy chain H4
70 kDa inter-alpha-trypsin inhibitor heavy chain H4
Proline-rich (PRR) potential bioactive peptide
Abolishes palmitoylation; when associated with S-402 and S-403.
Abolishes palmitoylation; when associated with S-402 and S-405.
Abolishes palmitoylation; when associated with S-403 and S-405.
Associated with increased susceptibility for Hirschsprung disease; sex-dependent gene dosage effect.
In HSCR2; decreased calcium release; no effect on cell membrane location.
In HSCR2; familial; loss of cell membrane location; new cytoplasmic location.
Probable disease-associated variant found in patients with Waardenburg syndrome 2; decreased calcium release upon endothelin 3 exposure; loss of downstream pathway activation upon endothelin 3 exposure; no effect on cell membrane location; no effect on internalization upon endothelin 3 exposure.
Probable disease-associated variant found in patients with Waardenburg syndrome 2; loss of cell membrane location; new cytoplasmic location.
Essential for receptor binding and receptor activation
In HH13; significantly reduced efficacy as well as potency.
Found in a patient with nephrotic syndrome; unknown pathological significance.
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
Found in a patient with multiple primary melanoma; partial loss of CDK4 binding.
Found in seminoma and medulloblastoma tissues from Li-Fraumeni syndrome patients carrying a mutation in TP53; somatic mutation.
Found in some patients with melanoma; loss of CDK4 binding.
Found in some patients with melanoma; partial loss of CDK4 binding.
In CMM2 and FAMMMPC; impairs the function.
In CMM2; also found in a biliary tract tumor and a patient with uveal melanoma; partial loss of CDK4 binding.
In CMM2; also found in a lung tumor and a prostate tumor.
In CMM2; also found in head and neck tumor; somatic mutation.
In CMM2; requires 2 nucleotide substitutions.
In a biliary tract tumor and a familial melanoma.
In a pancreas tumor and a melanoma; loss of CDK4 binding.
In a pancreas tumor; also found in head and neck tumor.
In an esophagus tumor; also found in head and neck tumor; also found in a lung tumor.
In pancreas carcinoma; somatic mutation; partial loss of CDK4 binding.
In some patients with melanoma; impairs the function.
Abolishes disulfide reductase activity; when associated with A-161; A-483 and A-591.
Abolishes disulfide reductase activity; when associated with A-161; A-483 and A-703.
Abolishes disulfide reductase activity; when associated with A-161; A-591 and A-703.
Abolishes disulfide reductase activity; when associated with A-483; A-591 and A-703.
Prevents interaction with HSPA5, leading to prolonged interaction with substrate proteins.
Gamma-aminobutyric acid receptor subunit rho-2
Abolishes interaction with KMT2A. Abolishes inhibition of KMT2A activity.
Expected to disrupt peptidylproline binding. Decreases interaction with KMT2A. Abolishes inhibition of KMT2A activity.
Expected to disrupt proline isomerase activity. Abolishes inhibition of KMT2A activity; when associated with A-191.
Expected to disrupt proline isomerase activity. Abolishes inhibition of KMT2A activity; when associated with A-196.
Strongly decreased affinity for KMT2A. Decreased affinity for RNA.
Abolishes interaction with TNPO1, TNPO1-mediated nuclear import and nuclear location.
C-terminal extension of DRBM 3 and constituent of a bi-partite nuclear localization signal
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
N-terminal extension of DRBM 3 and constituent of a bi-partite nuclear localization signal
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 allele GSTO1*B; decreased protein stability.
In allele GSTO1*C; no effect on protein stability.
In Seattle-1; may contribute to the development of familial combined hyperlipidemia.
In Seattle-2; may contribute to the development of familial combined hyperlipidemia.
In allele APOA-IV*0 and allele APOA-IV*5; allele APOA-IV*5 is further defined by a silent nucleotide substitution.
In allele APOA-IV*0A; associated with H-380.
In allele APOA-IV*1A and allele Budapest-1.
In allele APOA-IV*2 and allele APOA-IV*0A; associated with E-187 in allele APOA-IV*0A.
Inositol 1,4,5-trisphosphate receptor type 2
In SPGF73; unknown pathological significance.
Hydroxyacylglutathione hydrolase-like protein
Decreased S-adenosyl-L-methionine binding and methyltransferase activity in absence of RAMAC; when associated with E-409. Decreased interaction with RAMAC; when associated with E-409.
Decreased S-adenosyl-L-methionine binding and methyltransferase activity in absence of RAMAC; when associated with E-413. Decreased interaction with RAMAC; when associated with E-413.
Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 103-AAAAA-107 and I-127.
Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 80-AAAA-83 and 103-AAAAA-107.
Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 80-AAAA-83 and I-127.
Increased S-adenosyl-L-methionine binding and methyltransferase activity in absence of RAMAC; when associated with E-450. No change in interaction with RAMAC; when associated with E-450.
Increased S-adenosyl-L-methionine binding and methyltransferase activity in absence of RAMAC; when associated with E-452. No change in interaction with RAMAC; when associated with E-452.
Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-178. Complete restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-178. Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-178. Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-178; C-393 and C-398. Partially restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-178; C-393 and C-398.
Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-178; C-393 and C-417. Partially restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-178; C-393 and C-417.
Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-178; C-398 and C-417. Partially restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-178; C-398 and C-417.
Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-417. Complete restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-417. Loss of methyltransferase activity in presence or absence of RAMAC; when associated with C-417; C-393 and C-398. Partially restored RAMAC-mediated methyltransferase activity under reducing conditions; when associated with C-417; C-393 and C-398.
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
In ADHD7; has severely reduced solubility; is completely inactive; loss of function may lead to a reduced serotonin synthesis.
Linked with susceptibility to major depressive disorder; may be due to a rare RNA editing event; 80% loss of function; decreases solubility; decreases thermal stability; reduces catalytic activity.
May be associated with susceptibility to bipolar affective disorder; decreases solubility; decreases thermal stability; catalytic activity as the wild type; moderate loss-of-function observed manifested via stability and solubility effect.
Moderate loss-of-function observed manifested via stability and solubility effect.
The property of the variant is indistinguishable from the wild-type.
Eukaryotic translation initiation factor 3 subunit L
Breakpoint for translocation to form BIRC2-MALT1
Mucosa-associated lymphoid tissue lymphoma translocation protein 1
Slight decrease in NF-kappa-B activation.
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.
Impairs formation of heterotetramers with MAP2K1, but not the formation of heterodimers.
In HLD23; shows decreased beta-catenin binding.
In BCD; impaired omega hydroxylase activity.
Complete loss of phosphatase activity. Does not affect glycogen binding.
Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C.
Complete loss of phosphatase activity. No effect on glycogen binding.
Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2.
Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity.
Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1.
Glucan phosphatase signature motif CXAGXGR
Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding.
In EPM2; abolishes interaction with NHLRC1.
In EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; atypical form; does not affect glycogen binding.
In EPM2; atypical form; learning difficuties with childhood-onset.
In EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2.
In EPM2; does not affect glycogen binding.
In EPM2; impaired phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; impairs protein stability; affects phosphatase activity; abolishes glycogen binding; abolishes phosphatase activity with insoluble glucan; disrupts the interaction with PPP1R3C.
In EPM2; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C.
In EPM2; results in ubiquitin-positive perinuclear aggregates; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein.
In EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C.
In EPM2; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding.
Loss of phosphatase activity. Abolishes glycogen binding.
Loss of phosphatase activity. No effect on glycogen binding.
No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.
Partial loss of phosphatase activity. Abolishes homodimerization. Abolishes interaction with NHLRC1, PPP1R3C and PRKAA2. Does not affect glycogen binding. Reduces stability of the protein.
Partial loss of phosphatase activity. Increases interaction with NHLRC1. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. Does not affect binding to carbohydrate. Does not affect homodimerization.
Strongly decreased phosphatase activity. No effect on glycogen binding.
Strongly reduces phosphatase activity. Strongly reduces glycogen binding.
Does not affect mitochondrial location but reduces interaction with CLCC1.
Does not affect mitochondrial location or interaction with CLCC1.
Non-structural maintenance of chromosomes element 1 homolog
Single-pass membrane and coiled-coil domain-containing protein 4
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.
In variant Michigan-1; confers enhanced esterase activity and an additional zinc binding site.
Heparan sulfate glucosamine 3-O-sulfotransferase 2
WD repeat, SAM and U-box domain-containing protein 1
No effect on inhibition of cell death. No effect on interaction with INPP5D, PTPN6 and PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-662 and F-692. Alters binding with PTPN6 and PTPN11; when associated with F-692. Decreases calcium influx inhibition; when associated with F-650 and F-662. Decreases calcium influx inhibition; when associated with F-650 and F-692. Decreases calcium influx inhibition; when associated with F-692.
No effect on inhibition of cell death. No effect on interaction with INPP5D, PTPN6 and PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-662; F-692 and F-722. Alters binding with SYK and ZAP70; when associated with F-662. Decreases calcium influx inhibition; when associated with F-662 and F-722. Decreases calcium influx inhibition; when associated with F-692 and F-722.
Partially reduces inhibition of cell death. Decreases interaction with INPP5D and PTPN11. No effect on interaction with PTPN6. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-662 and F-722. Alters binding with PTPN6 and PTPN11; when associated with F-772. Decreases calcium influx inhibition; when associated with F-650 and F-722. Increases calcium influx inhibition; when associated with F-650 and F-662. Decreases calcium influx inhibition; when associated with F-722.
Reduces inhibition of cell death. Decreases interaction with INPP5D and PTPN6. No effect on interaction with PTPN11. Loss of phosphorylation, calcium influx inhibition and interaction with INPP5D, PTPN6 and PTPN11; when associated with F-650; F-692 and F-722. Alters binding with SYK and ZAP70; when associated with F-650. Decreases calcium influx inhibition; when associated with F-650 and F-722. Increases calcium influx inhibition; when associated with F-650 and F-722.
Odontogenic ameloblast-associated protein
Found in a patient with global developmental delay, spasticity and epilepsy; unknown pathological significance.
Myeloid cell nuclear differentiation antigen
(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 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.
Affects transporter activity; reduction of MPP(+) uptake when associated with V-408.
Affects transporter activity; reduction of MPP(+) uptake; reduction of serum O-isobutanoyl-(R)-carnitine levels; reduction of MPP(+) uptake when associated with V-408.
Affects transporter activity; reduction of MPP(+), serotonin and TEA uptake.
Affects transporter activity; reduction of MPP(+), serotonin and TEA uptake; no MPP(+) uptake when associated with L-160.
Affects transporter activity; reduction of TEA uptake; reduction o MPP(+) uptake when associated with V-408; largely localized to the plasma membrane.
Does not affect transporter activity; no changes in MPP(+) uptake when associated with F-14; no changes in MPP(+) uptake when associated with F-85; no changes in MPP(+) uptake when associated with L-189; no changes in MPP(+) uptake when associated with H-342; no changes in MPP(+) uptake when associated with M-420 del; no changes in MPP(+) uptake when associated with I-440; no changes in MPP(+) uptake when associated with I-461; no changes in MPP(+) uptake when associated with M-488; reduction of MPP uptake when associated with C-61; no MPP(+) uptake when associated with V-220; reduction of 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; increased MPP(+) uptake when associated with V-408.
Increased fenoterol uptake. Increased fenoterol affinity. No change in trospium uptake. No change in terbutaline uptake. No change in terbutaline affinity.
No change in fenoterol uptake. Decreased trospium uptake. Decreased trospium affinity.
No change in fenoterol uptake. No change in trospium uptake. No change in terbutaline uptake.
No changes in MPP(+) uptake when associated with V-408.
No changes in MPP(+) uptake; when associated with V-408.
No changes in both MPP(+) and TEA uptake; abolishes MPP(+) uptake when associated with S-401; largely localized to the plasma membrane.
Reduction of serum O-isobutanoyl-(R)-carnitine levels; no change in MPP(+) uptake; no changes in MPP(+) uptake when associated with V-408.
Reduction of the localization to the basolateral membrane; no MPP(+) uptake when associated with V-408.
DNA methyltransferase 1-associated protein 1
In NEDGS; unknown pathological significance.
Abolished stimulation of KDM1B demethylase activity, reduced affinity for histone H3 of the dimer with KDM1B, but normal KDM1B-binding.
Decreased interaction with GATA4; decreased synergistic activation of GATA4 target genes transcription; detrimental effect on cardiomyocyte differentiation.
Impaired KDM1B-binding and abolished stimulation of KDM1B demethylase activity.
Impaired KDM1B-binding and abolished stimulation of KDM1B demethylase activity; when associated with A-219.
Impaired KDM1B-binding and abolished stimulation of KDM1B demethylase activity; when associated with A-223.
Loss of tetramerization and protein stability.
No effect on tetramerization or protein stability.
Required to promote KDM1B demethylase activity toward histone H3K4me1 and H3K4me2
Slightly reduced stimulation of KDM1B demethylase activity, but normal KDM1B-binding.
Completely abolishes interaction with KLC1.
Nuclear nucleic acid-binding protein C1D
In CHNG7; loss of thyrotropin-releasing hormone receptor activity.
In CHNG7; loss of thyrotropin-releasing hormone receptor activity; no effect on localization to plasma membrane.
Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform
Transcription termination factor 3, mitochondrial
Cell division cycle protein 20 homolog B
Impairs interaction with CDC42 and reduces CDC42-induced actin assembly.
Impairs interaction with WASL and reduces CDC42-induced actin assembly.
Interaction with DAAM1, DIAPH1 and DIAPH2
Mediates end-to-end attachment of dimers
Loss of deubiquitinating activity due to stabilization of the autoinhibited conformation.
Loss of deubiquitinating activity. Increased ability to interact with polyubiquitin.
Loss of deubiquitinating activity; when associated with N-358.
Loss of deubiquitinating activity; when associated with S-194.
Reduces deubiquitinating activity with 'Lys-11'-linked ubiquitin chains; no effect on cleavage of 'Lys-48'-linked and 'Lys-63'-linked ubiquitin chains.
Stabilizes the conformation of the regulatory loop
Strongly reduces deubiquitinating activity.
Abolishes sumoylation. Exclusive nucleoplasmic location. Increase in binding the E-selectin promoter.
Completely abolishes MAPK9- and adenovirus E1A-mediated transactivation; when associated with D-51.
Completely abolishes MAPK9- and adenovirus E1A-mediated transactivation; when associated with D-53.
Cyclic AMP-dependent transcription factor ATF-7
Greatly reduced JNK2- or adenovirus E1A-mediated transactivation. Abolishes adenovirus 2 E1A-mediated transactivation; when associated with A-51; A-53 and G-101.
No effect on binding adenovirus 2 E1A. Abolishes ATF7-mediated E1A responsiveness.
No effect on transactivation; when associated with A-145.
No effect on transactivation; when associated with A-147.
Severely reduced TAF12-induced transcriptional activity. No effect on MAPK9-mediated phosphorylation; when associated with A-51. Greatly reduces MAPK9- and adenovirus E1A-mediated transactivation; when associated with A-51 and G-101. Abolishes adenovirus 2 E1A-mediated transactivation; when associated with A-14; A-51 and G-101.
Severely reduced TAF12-induced transcriptional activity. No effect on MAPK9-mediated phosphorylation; when associated with A-53. Greatly reduces MAPK9- and adenovirus E1A-mediated transactivation; when associated with A-53 and G-101. Abolishes adenovirus 2 E1A-mediated transactivation; when associated with A-14; A-53 and G-101.
Severely reduced TAF12-induced transcriptional activity; when associated with D-33.
Severely reduced TAF12-induced transcriptional activity; when associated with S-35.
Severely reduced TAF12-mediated enhancement of transcriptional activity.
Some reduction in transactivation but, completely abolishes MAPK9-mediated activation. Abolishes MAPK9-mediated and greatly reduces adenovirus E1A-mediated transactivation; when associated with A-51 and A-53. Abolishes adenovirus 2 E1A-mediated transactivation; when associated with A-14; A-51 and A-53.
BTB/POZ domain-containing protein KCTD11
Potassium channel tetramerisation-type BTB
Decreases methylcobalamin levels and mildly increases adenosylcobalamin levels.
Decreases methylcobalamin levels, but increases adenosylcobalamin levels.
Decreases methylcobalamin levels, but increases adenosylcobalamin levels. No effect on interaction with MMACHC.
Decreases methylcobalamin levels. Impairs interaction with MMACHC.
Decreases methylcobalamin levels. No effect on interaction with MMACHC.
In MAHCD; cblD variant 1; decreases methylcobalamin levels and increases adenosylcobalamin levels; no effect on interaction with MMACHC.
In MAHCD; cblD variant 1; impairs interaction with MMACHC.
Marginally decreases methylcobalamin levels and strongly increases adenosylcobalamin levels.
Mildly decreases methylcobalamin levels and strongly increases adenosylcobalamin levels.
Abolished homooligomerization and formation of BCL10-nucleating filaments.
Caspase recruitment domain-containing protein 9
Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B.
Disruption of the linker region, relieving autoinhibition and leading to activation of NF-kappa-B. Constitutively forms BCL10-nucleating filaments.
In IMD103; abolished homooligomerization and formation of BCL10-nucleating filaments; reduced cytokine production in response to C.albicans infection; reduced production IgG antibodies in response to C.albicans infection.
In IMD103; decreased production of cytokines in CD4(+) Th17 cells.
In IMD103; does not affect formation of the CBM complex but impairs formation of a complex with RASGRF1.
In IMD103; reduced cytokine production in response to C.albicans infection.
In IMD103; reduced cytokine production in response to C.albicans infection; does not affect NF-kappa-B transcriptional activity.
In IMD103; reduced cytokine production in response to C.albicans infection; impaired NF-kappa-B transcriptional activity.
In IMD103; reduced cytokine production in response to C.albicans infection; impaired NF-kappa-B transcriptional activity; reduced production IgG antibodies in response to C.albicans infection.
In IMD103; reduced production IgG antibodies in response to C.albicans infection.
Reduced cytokine production in response to C.albicans infection. Impaired NF-kappa-B transcriptional activity. Does not affect interaction with BCL10.
In MMYAT; autosomal dominant; patient cells show decreased mitochondrial fusion and mitochondrial network formation; patient cells show increased mitochondria aggregation and fragmentation.
In MMYAT; unknown pathological significance.
Microtubule-associated proteins 1A/1B light chain 3C
Phospho-mimetic mutant; impaired interaction with ATG4 proteins, preventing cleavage at the C-terminus, conjugation to phosphatidylethanolamine and localization to autophagosomes.
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).
Phosphorylated at one of three serine residues
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.
Required for interaction with the sumoylated form of CCAR2
Pleckstrin homology-like domain family B member 1
In NEDGEF; increased DNA damage is detected in patient fibroblasts suggesting decreased fuction in DNA repair; no protein is detected in patient fibroblasts.
In NEDGEF; increased DNA damage is detected in patient fibroblasts suggesting decreased fuction in DNA repair; reduced protein localization to the nucleus in patient fibroblasts.
Abolished interaction with EIF4ENIF1/4E-T without affecting interaction with DDX6; when associated with E-22.
Abolished interaction with EIF4ENIF1/4E-T without affecting interaction with DDX6; when associated with E-29.
In LHON; possible rate primary mutation.
Found in a patient with atypical hemolytic uremic syndrome.
Found in patients with atypical hemolytic uremic syndrome.
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.
Found in a patient with Nakajo syndrome who also carries a mutation in PSMB8; unknown pathological significance; patients' cells show reduction of proteasome content and endopeptidase activity of the proteasome.
Haloacid dehalogenase-like hydrolase domain-containing 5
Cilia- and flagella-associated protein 73
Acyl-coenzyme A thioesterase 13, N-terminally processed
N-acetylthreonine; in Acyl-coenzyme A thioesterase 13, N-terminally processed
Abolishes autoubiquitination; when associated with A-13.
Abolishes autoubiquitination; when associated with A-59.
Loss of autoubiquitination and reduced ubiquitination of BCL2L1; when associated with S-13.
Loss of autoubiquitination and reduced ubiquitination of BCL2L1; when associated with S-16.
Loss of autoubiquitination but no effect on ubiquitination of BCL2L1; when associated with R-101 and R-105.
Loss of autoubiquitination but no effect on ubiquitination of BCL2L1; when associated with R-28 and R-101.
Loss of autoubiquitination but no effect on ubiquitination of BCL2L1; when associated with R-28 and R-105.
Vitelline membrane outer layer protein 1 homolog
Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]
May increase risk to develop PFB; the variant is disruptive at late stages of filament assembly compromising the aggregation of keratin molecules into intermediate filaments.
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.
In ANPH2; no effect on protein abundance; loss of protein serine/threonine kinase activity; loss of autophosphorylation at T-208; loss of function in regulation of hippo signaling.
In an ovarian Endometrioid carcinoma sample; somatic mutation.
Loss of autophosphorylation, kinase activity and of anti-apoptotic activity.
Interchain (with KASH domain-containing nesprins)
Sufficient for interaction with SYNE1 and SYNE2
Guanine nucleotide exchange factor for Rab-3A
Necessary and sufficient for interaction with ARPC2
Impairs interaction with the Elongin BC complex; when associated with F-147.
Impairs interaction with the Elongin BC complex; when associated with P-143.
Mediator of RNA polymerase II transcription subunit 8
Cytoplasmic; when associated with A-273.
Cytoplasmic; when associated with A-276.
Lymphocyte antigen 6 complex locus protein G6f
No phosphorylation. No interaction with GRB2 and GRB7. No phosphorylation increase of p42/44 MAP kinase.
Abolished protease activity and ability to mediate cleavage of DELE1 in response to mitochondrial stress. Abolished ability to mediate cleavage of PINK1 in depolarized mitochondria.
Abolishes ability to cleave OPA1 at S1 position.
Metalloendopeptidase OMA1, mitochondrial
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.
ATPase family AAA domain-containing protein 3B
Sterile alpha motif domain-containing protein 15
Pleckstrin homology-like domain family A member 3
Cytochrome c oxidase assembly protein COX14
Necessary for polyamine uptake stimulation
Abolished formation of N(7)-methylguanine in tRNAs.
Does not affect formation of N(7)-methylguanine in tRNAs.
Found in a patient with lung cancer; abolished formation of N(7)-methylguanine in tRNAs.
In GAMOS6; abolished formation of N(7)-methylguanine in tRNAs.
In GAMOS6; unknown pathological significance.
In MIGSB; abolished formation of N(7)-methylguanine in tRNAs.
Reduced formation of N(7)-methylguanine in tRNAs.
Slightly reduced formation of N(7)-methylguanine in tRNAs.
tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4
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.
Decreased of about 30% in transport activity.
Decreased of about 35% in transport activity. Alters the pH and voltage modulation of the transporter.
Decreased of about 60% in transport activity. Does not alter the substrate selectivity of SLC39A2.
Decreased of about 60% in transport activity. Loss of pH dependence for transport activity.
Decreased of about 78% in transport activity.
Decreases of about 72% in transport activity.
Does not affect transport activity. Reduces affinity for H(+).
Does not affect transport kinetics parameters. Exhibits a broader substrate selectivity.
Does not alter the substrate selectivity of SLC39A2.
Exhibits a broader substrate selectivity.
Increased of about 35% in transport activity.
Increased of about 65% in transport activity. Does not change H(+) affinity.
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 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 T1D20; decreased 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.
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.
ETS translocation variant 3-like protein
Epidermal growth factor receptor kinase substrate 8
Coiled-coil domain-containing protein 122
Glycerophosphoinositol inositolphosphodiesterase GDPD2
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.
Coiled-coil domain-containing protein 192
Does not affect location in mitochondria; fails to rescue the increased accumulation of the level of mature MT-ND3, MT-CO3, MT-CYB or MT-ND5 mRNA in TBRG4-deficient cells; does not abolish the accumulation of the MT-ND5-CYB precursor RNA in a TBRG4-deficient cell line.
NACHT, LRR and PYD domains-containing protein 13
In DFNB98; unknown pathological significance.
In ECTD14 and STHAG10; unknown pathological significance.
In ECTD14; unknown pathological significance.
In STHAG10; unknown pathological significance.
Thrombospondin-type laminin G domain and EAR repeat-containing protein
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.
Ceroid-lipofuscinosis neuronal protein 6
In CLN4A; requires 2 nucleotide substitutions.
In CLN6; decreased protein level, resulting from ER membrane-to-cytosol dislocation of the protein followed by proteasome degradation..
In CLN6; unknown pathological significance.
Ankyrin repeat domain-containing protein SOWAHD
Apoptosis-inducing factor 1, mitochondrial
Disrupts dimerization. Disrupts dimerization; when associated with A-477.
Disrupts dimerization. Lower efficiency in stabilizing charge-transfer complexes upon coenzyme reduction.
Disrupts dimerization; when associated with A-443--445-A.
In CMTX4; increases affinity for NADH and electron transfer activity; increases affinity for DNA, resulting in increased apoptosis; no effect on interaction with CHCHD4.
In COXPD6; higher DNA binding affinity, partially impaired flavin binding and association with increased parthanatos-linked cell death.
In COXPD6; reduced protein amount in muscle compared to controls; no effect on reduction with NADH; strongly decreased NADH oxidase activity; no effect on dimerization; no effect on DNA-binding.
In COXPD6; with early-onset severe motor neuron involvement; decreased protein levels; decreased oxidoreductase activity on cytochrome C; slowered reduction with NADH; strongly decreased NADH oxidase activity; strongly decreased NADH oxidase activity; no effect on DNA-binding.
In COXPD6; with prenatal ventriculomegaly and severe postnatal encephalomyopathy; no effect on redox potential; slowered reduction with NADH; strongly decreased NADH oxidase activity; strongly decreased NADH oxidase activity; no effect on DNA-binding; decreased interaction with CHCHDE.
In DFNX5; unknown pathological significance.
In SEMDHL; severe decrease of protein expression.
Increases protein dimerization at lower NADH levels.
Mitochondrial apoptosis-inducing factor C-terminal
Probable disease-associated variant found in patient with mitochondrial encephalomyopathy with moderate clinical severity and slow progressive course despite early onset as well as and cerebellar involvement; decreased protein level; strongly decreased redox potential; strongly decreased NADH oxidase activity; no effect on DNA-binding.
Decreases activation by Zn(2+). Abolishes activation by Zn(2+); when associated with A-17.
Decreases activation by Zn(2+). Abolishes activation by Zn(2+); when associated with A-19.
Induces very high constitutive activity and eliminates Zn(2+)-induced activation.
Not affect constitutive or Zn(2+)-induced activation.
3-oxoacyl-[acyl-carrier-protein] reductase
Important for interaction with acyl carrier protein (ACP)
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.
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.
In ICF1; unknown pathological significance.
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7 and isoform 8.
Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity.
Abolishes 'Lys-48'- and 'Lys-63'-specific deubiquitinase activity. Impairs 'Lys-63'-specific deubiquitinase activity toward MYD88 substrate.
Abolishes 'Lys-63'-specific deubiquitinase activity by impairing the affinity for 'Lys-63'-linked ubiquitin chain substrate.
Abolishes interaction with USP7 and USP9X deubiquitinases.
Could be associated with cerebellar ataxia and hypogonadotropic hypogonadism.
Decreases 'Lys-63'-specific deubiquitinase activity. Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204.
Loss of 'Lys-63'-specific deubiquitinase activity; when associated with A-204.
In ARCI5; results in decreased synthesis of omega-hydroxyceramides.
In ARCI5; results in impaired synthesis of omega-hydroxyceramides.
Ultra-long-chain fatty acid omega-hydroxylase
Beta-chain polymerization, binding distal domain of another fibrin
Cleavage; by hementin; to prevent blood coagulation
Cleavage; by plasmin; to break down fibrin clots
Cleavage; by thrombin; to release fibrinopeptide B
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.
Essential for interaction with CBLN1; modulates interaction affinity with NLGN1, NLGN2 and NLGN3; prevents interaction with DAG1/alpha-dystroglycan; modulates interaction with alpha-latrotoxin
O-linked (Xyl...) (heparan sulfate) serine
Abolishes GTPase activity and decreases association with GPN3.
Gly-Pro-Asn (GPN)-loop; involved in dimer interface
Stabilizes the phosphate intermediate; shared with dimeric partner
Ras-associating and dilute domain-containing protein
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3B
Interacts with target acceptor peptide in protein substrate
Transcription elongation factor A protein 3
Dimethylglycine dehydrogenase, mitochondrial
Glycine cleavage T-protein C-terminal barrel
In DMGDHD; shows 10 fold lower catalytic efficiency due to lower cofactor saturation and reduced thermal stability.
Found in a case of radioulnar synostosis; unknown pathological significance.
Found in a family with radioulnar synostosis; 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.
10 X 5 AA repeats of C-C-[CDPQRWG]-[APRS]-[CIPSTVD]
10 X 5 AA repeats of C-C-[CDPQRW]-[ADPRS]-[CIPSTV]
Found in a patient with nephrotic syndrome; unknown pathological significance; no effect on protein localization.
KN motif and ankyrin repeat domain-containing protein 4
Fails to interact with clathrin heavy chain. Diffuse localization throughout the cell.
In IMD85; decreases interaction with TOLLIP and UBC.
Reduced binding to phosphatidylinositol monophosphates.
Reduced interaction with TOLLIP. Reduced localization to endosomal vesicles.
Reduced interaction with clathrin heavy chain.
Target of Myb1 membrane trafficking protein
In HMAKD; complete loss of adenosine kinase activity.
In HMAKD; the mutant shows some residual adenosine kinase activity.
HLA class I histocompatibility antigen, alpha chain F
Impairs the anterograde ER-to-Golgi transport.
Impairs the interaction with 14-3-3 proteins.
Impairs the interaction with coat protein complex II; impairs the anterograde ER-to-Golgi transport.
Sorting signal sequence; Golgi-retention signal; ER-retention signal
Impaired acetylation, leading to promote rRNA processing; when associated with R-12.
Impaired acetylation, leading to promote rRNA processing; when associated with R-25.
Mimics acetylation, leading to impaired rRNA processing; when associated with Q-12.
Mimics acetylation, leading to impaired rRNA processing; when associated with Q-25.
U3 small nucleolar RNA-interacting protein 2
In NEM8; unknown pathological significance.
Pleckstrin homology domain-containing family B member 2
Found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; requires 2 nucleotide substitutions; uncertain pathological significance.
Found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; uncertain pathological significance.
Found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; unknown pathological significance; retains its ability to transport iodide in vitro.
Found at heterozygosity in a patient with non-syndromic deafness; uncertain pathological significance.
In DFNB4 and PDS; common mutation in Korea and Japan.
In DFNB4 and PDS; does not affect protein localization to cell membrane; does not affect iodide transport.
In DFNB4 and PDS; fails to localize to cell membrane; abolishes iodide transport.
In DFNB4 and PDS; severely reduces iodide transport without affecting protein localization to cell membrane.
In DFNB4; also found at heterozygosity in a patient with non-syndromic deafness; uncertain pathological significance; loss of cell membrane localization, loss of chloride tranport, chloride-bicarbonate exchanger and chloride-iodide exchanger activities.
In PDS and DFNB4; also found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; uncertain pathological significance.
In PDS and DFNB4; common mutation; fails to localize to cell membrane; abolishes iodide transport.
In PDS and DFNB4; partially affects protein localization to cell membrane; abolishes iodide transport.
In PDS; also found at heterozygosity in a patient with hearing loss and unilateral enlargement of the vestibular aqueduct; uncertain pathological significance.
In PDS; fails to localize to cell membrane; abolishes iodide transport.
In PDS; partially affects protein localization to cell membrane; abolishes iodide transport.
In PDS; retains residual transport function.
In Pendred syndrome/deafness individuals.
Required for interaction with TGFBR1 and promotion of TGF-beta signaling
High affinity receptor-binding region which is also known as the TP508 peptide
In FA2D; prothrombin type 3; variant confirmed at protein level.
Interchain (between light and heavy chains)
Loss of catalytic activity; no effect on cleavage at R-198 by factor Xa.
Pleckstrin homology domain-containing family S member 1
Melanoma-derived growth regulatory protein
In LQT9; increase in late sodium current.
In RMD2; decreased surface expression of the CAV3 protein.
In a patient with mild proximal myopathy.
Pseudouridine synthase I TruA alpha/beta
In MACID; likely benign variant; does not affect GFAP transcriptional activation.
In MACID; significant decrease of GFAP transcriptional activation.
Abolishes binding to ubiquitin; Abolishes recruitment to DNA lesion sites.
Reduces sumoylation. Does not reduce transcriptional repressive activity. Inhibits sumoylation but does not reduce transcriptional repressive activity; when associated with R-265.
Reduces sumoylation. Inhibits transcriptional repressive activity. Inhibits sumoylation and reduces transcriptional repressive activity; when associated with R-328.
Zinc finger and BTB domain-containing protein 1
Basic helix-loop-helix ARNT-like protein 2
In isoform 2, isoform 3, isoform 4, isoform 6, isoform 7, isoform 8 and isoform 9.
In isoform 3, isoform 4, isoform 5, isoform 6 and isoform 9.
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.
Loss of phosphorylation and its ability to potentiate JUN transcriptional activator activity.
ATP-sensitive inward rectifier potassium channel 12
Does not disrupt growth-inhibiting activity.
Insulin-like growth factor-binding protein 2
RNA-binding motif protein, Y chromosome, family 1 member B
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 SEC11C
Slight reduction in catalytic activity; when associated with D-109.
Slight reduction in catalytic activity; when associated with R-128.
Necessary and sufficient for ORC complex assembly
In CDG2R; impairs export from the ER and cleavage, increases N-glycosylation post-translational modification which targets the misfolded protein to degradation via the ER-associated degradation pathway, results in loss of interaction with ATP6AP1.
In CDG2R; increases degradation rate via the ER-associated degradation pathway; loss of interaction with ATP6AP1.
Increases cleavage and stability and enhancing localization to the Golgi; when associated with Q-346.
Increases cleavage and stability enhancing localization to the Golgi; when associated with Q-348.
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
Coiled-coil domain-containing protein 185
Neuronal vesicle trafficking-associated protein 1
Abolishes interaction with HSP90AB1 and impairs interaction with HSPA8.
Impairs interaction with HSP90AB1 and HSPA8.
Membrane-spanning 4-domains subfamily A member 15
Induces a stronger permeability to cations.
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 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.
Does not affect activation by nicked DNA, while it prevents activation by a 3'-overhang substrate.
Protein mono-ADP-ribosyltransferase PARP3
Abolishes the ability to activate signaling pathways that mediate mobilization of cytoplasmic Ca(2+). Abolishes the ability to restore normal B cell functions and responses to antigenic stimuli.
No effect on the ability to complement impaired B cell development and functions; when associated with F-348.
No effect on the ability to complement impaired B cell development and functions; when associated with F-378.
No effect on the ability to complement impaired B cell development and functions; when associated with F-409.
No effect on the ability to complement impaired B cell development and functions; when associated with F-421.
No effect on the ability to complement impaired B cell development and functions; when associated with F-439.
No effect on the ability to complement impaired B cell development and functions; when associated with F-461.
Strongly reduced tyrosine phosphorylation; when associated with F-500. Abolishes activation of signaling pathways that mediate mobilization of cytoplasmic Ca(2+); when associated with F-500. Abolishes the ability to complement impaired B cell development and functions; when associated with F-500.
Strongly reduced tyrosine phosphorylation; when associated with F-531. Abolishes activation of signaling pathways that mediate mobilization of cytoplasmic Ca(2+); when associated with F-531. Abolishes the ability to complement impaired B cell development and functions; when associated with F-531.
(Microbial infection) Interaction with Ebolavirus VP30
Ubiquitin-associated domain-containing protein 2
In isoform 2, isoform 4, isoform 6 and isoform 10.
In isoform 7, isoform 9, isoform 10, isoform 11 and isoform 12.
Disintegrin and metalloproteinase domain-containing protein 30
Loss of enzymatic activity; when associated with L-338 and L-342.
Loss of enzymatic activity; when associated with L-338 and L-348.
Loss of enzymatic activity; when associated with L-342 and L-348.
Tyrosine-protein phosphatase non-receptor type 18
Effector domain involved in lipid-binding and calmodulin-binding
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.
Myb/SANT-like DNA-binding domain-containing protein 3
Ankyrin repeat domain-containing protein 33B
Reduced ability to promote replication fork progression and integrity following DNA damage.
Loss of interaction with ECT2 and PRKCI.
Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-28.
Slight decrease of interaction with PRKCI. Loss of interaction with PRKCI; when associated with A-89.
Inhibitor of growth protein N-terminal histone-binding
Necessary for transcriptional transactivation
Biogenesis of lysosome-related organelles complex 1 subunit 2
Leukocyte immunoglobulin-like receptor subfamily A member 1
No effect on transcriptional repression on KRT4 promoter.
Partially abrogates repressive effect on the KRT4 promoter.
Partially abrogates repressive effect on the KRT4 promoter; when associated with A-315.
Partially abrogates repressive effect on the KRT4 promoter; when associated with A-319.
Glucose-dependent insulinotropic receptor
Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-24 or Ser-256. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with A-24 and A-256. Targeted to the nucleus and enhances transactivation; when associated with A-24.
Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-256 or Ser-319. Also inhibits binding of 14-3-3 proteins. Nuclear in unstimulated cells, and little export to cytoplasm on IGF1 stimulation. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with A-256 and A-319. Targeted to the nucleus and enhances transactivation; when associated with A-319.
Abolishes STK4/MST1-mediated phosphorylation.
Completely abolishes PKB/AKT1-mediated phosphorylation at all three sites, and inhibits binding of 14-3-3 proteins. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with or without A-24 and A-319. Nuclear in unstimulated cells, and little export to cytoplasm on IGF1 stimulation. Abolishes the ability of IGF1 to suppress transactivation. Prevents T-24 and S-319 phosphorylation. Enhances transactivation; when associated with A-24 and A-319.
Disrupts DNA-binding; when associated with A-245.
Disrupts DNA-binding; when associated with A-248.
Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death; when associated with R-262 and R-265.
Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death; when associated with R-262 and R-274.
Inhibits interaction with ATG7 and FOXO1-acetylation-induced autophagic cell death; when associated with R-265 and R-274.
No targeting to the nucleus and disruption of DNA-binding.
Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK1
Reduces DNA binding, promotes nuclear exclusion and partially promotes T-24 and S-319 phosphorylation. Reduces DNA binding, does not promote nuclear exclusion but reduces transactivation; when associated with A-24 and A-319.
Targeted to the nucleus and enhances transactivation.
In AI1J; unknown pathological significance.
Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination.
Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-18.
Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-54.
Methylmalonyl-CoA epimerase, mitochondrial
Leucine-rich repeat-containing protein 39
Ankyrin repeat domain-containing protein 60
Post-GPI attachment to proteins factor 2
Guanylate cyclase soluble subunit beta-1
Coenzyme Q-binding protein COQ10 homolog B, mitochondrial
Dynein light chain Tctex-type protein 2B
Abolishes binding to H3K4me2 and H3K4me3.
Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-899 and A-1056.
Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-899 and A-954.
Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-954 and A-1056.
Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-899; A-954 and A-1056.
Does not alter iron-binding nor activates histone demethylase activity.
Glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1
Abolishes interaction with TP53, TP73, MAPK8 and ERBB4. Partial loss of interaction with TFAP2C. Loss of phosphorylation. Loss of the proapoptotic activity. Abolishes binding to VOPP1.
Found in a esophageal cancer sample; somatic mutation.
Found in a primary colorectal tumor and tumor cells.
In a primary colorectal tumor and a histiocytic lymphoma cell line.
No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with T-28.
No effect on interaction with TP53. Abolishes interaction with MAPK8; when associated with V-29.
RNA polymerase II subunit A C-terminal domain phosphatase SSU72
D-isomer specific 2-hydroxyacid dehydrogenase NAD-binding
D-isomer specific 2-hydroxyacid dehydrogenase catalytic
Glyoxylate reductase/hydroxypyruvate reductase
Alpha/beta hydrolase domain-containing protein 17B
HLA class I histocompatibility antigen, B alpha chain
In allele B*08:01, allele B*13:02, allele B*14:01, allele B*15:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*38:01 allele B*39:02, allele B*40:02, allele B*41:01, allele B*42:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*78:01 and allele B*82:01.
In allele B*08:01, allele B*13:02, allele B*14:01, allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*59:01 and allele B*78:01.
In allele B*08:01, allele B*13:02, allele B*14:01, allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*59:01 and allele B*78:01; requires 2 nucleotide substitutions.
In allele B*08:01, allele B*13:02, allele B*14:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*42:01, allele B*45:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*78:01, allele B*81:01 and allele B*82:01.
In allele B*08:01, allele B*13:02, allele B*15:01, allele B*35:01, allele B*40:01, allele B*41:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*78:01 and allele B*82:01.
In allele B*08:01, allele B*13:02, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*42:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*48:01, allele B*53:01, allele B*54:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*81:01 and allele B*82:01.
In allele B*08:01, allele B*14:01, allele B*18:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*41:01, allele B*42:01, allele B*54:01, allele B*55:01, allele B*59:01 and allele B*67:01; requires 2 nucleotide substitutions.
In allele B*08:01, allele B*35:01, allele B*51:01, allele B*53:01, allele B*59:01 and allele B*78:01.
In allele B*08:01, allele B*37:01, allele B*41:01, allele B*42:01, allele B*44:02, allele B*45:01 and allele B*82:01; requires 2 nucleotide substitutions.
In allele B*08:01; associated with increased risk for rheumatoid arthritis.
In allele B*13:02, allele B*14:01, allele B*15:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:02, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*78:01 and allele B*82:01.
In allele B*13:02, allele B*14:01, allele B*15:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*78:01 and allele B*82:01.
In allele B*13:02, allele B*14:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*78:01 and allele B*81:01.
In allele B*13:02, allele B*15:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*78:01 and allele B*82:01.
In allele B*13:02, allele B*15:01, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*40:02, allele B*44:02, allele B*46:01, allele B*47:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*78:01, allele B*81:01 and allele B*82:01.
In allele B*13:02, allele B*15:01, allele B*18:01, allele B*27:01, allele B*35:01, allele B*37:01, allele B*38:01, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01 and allele B*59:01.
In allele B*13:02, allele B*15:01, allele B*18:01, allele B*37:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01 and allele B*52:01.
In allele B*13:02, allele B*15:01, allele B*27:01, allele B*27:05, allele B*37:01, allele B*39:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*48:01, allele B*49:01, allele B*50:01, allele B*52:01, allele B*57:01 and allele B*58:01; requires 2 nucleotide substitutions.
In allele B*13:02, allele B*15:01, allele B*46:01 and allele B*57:01.
In allele B*13:02, allele B*15:01, allele B*46:01 and allele B*57:01; requires 2 nucleotide substitutions.
In allele B*13:02, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*40:02, allele B*44:02, allele B*47:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01, allele B*78:01, allele B*81:01 and allele B*82:01.
In allele B*13:02, allele B*18:01, allele B*27:01, allele B*27:05, allele B*35:01, allele B*37:01, allele B*40:02, allele B*44:02, allele B*47:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01, allele B*78:01 and allele B*81:01.
In allele B*13:02, allele B*18:01, allele B*27:01, allele B*27:05, allele B*37:01, allele B*40:02, allele B*44:02, allele B*47:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*59:01 and allele B*82:01.
In allele B*13:02, allele B*27:01, allele B*27:05, allele B*37:01, allele B*38:01, allele B*44:02, allele B*47:01, allele B*49:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01 and allele B*59:01; part of Bw4 motif involved in the recognition of KIR3DL1.
In allele B*13:02, allele B*27:01, allele B*27:05, allele B*37:01, allele B*38:01, allele B*44:02, allele B*49:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01 and allele B*59:01.
In allele B*13:02, allele B*27:01, allele B*27:05, allele B*37:01, allele B*44:02 and allele B*47:01.
In allele B*13:02, allele B*27:01, allele B*27:05, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*49:01, allele B*50:01 and allele B*73:01.
In allele B*13:02, allele B*27:01, allele B*38:01, allele B*44:02, allele B*49:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01 and allele B*59:01.
In allele B*13:02, allele B*27:01, allele B*38:01, allele B*44:02, allele B*49:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01, allele B*58:01 and allele B*59:01; requires 2 nucleotide substitutions.
In allele B*13:02, allele B*35:01, allele B*45:01, allele B*49:01, allele B*50:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*58:01, allele B*59:01 and allele B*82:01.
In allele B*13:02, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*49:01 and allele B*50:01.
In allele B*13:02, allele B*41:01, allele B*45:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*59:01, allele B*73:01 and allele B*78:01.
In allele B*13:02, allele B*45:01, allele B*49:01, allele B*50:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*59:01 and allele B*82:01; requires 2 nucleotide substitutions.
In allele B*13:02, allele B*51:01, allele B*52:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*59:01, allele B*73:01 and allele B*78:01.
In allele B*14:01, allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*45:01, allele B*46:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*58:01, allele B*59:01, allele B*67:01, allele B*73:01, allele B*78:01 and allele B*82:01.
In allele B*14:01, allele B*18:01, allele B*51:01, allele B*52:01, allele B*73:01 and allele B*78:01.
In allele B*14:01, allele B*27:01, allele B*27:05, allele B*37:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*49:01, allele B*50:01 and allele B*73:01.
In allele B*14:01, allele B*27:01, allele B*27:05, allele B*38:01 and allele B*73:01.
In allele B*14:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*67:01 and allele B*73:01.
In allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*38:01, allele B*39:02, allele B*40:01, allele B*41:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*47:01, allele B*49:01, allele B*50:01, allele B*53:01, allele B*58:01, allele B*67:01 and allele B*82:01.
In allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*45:01, allele B*46:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*58:01, allele B*59:01, allele B*73:01, allele B*78:01 and allele B*82:01.
In allele B*15:01, allele B*18:01, allele B*35:01, allele B*37:01, allele B*45:01, allele B*46:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*58:01, allele B*59:01, allele B*78:01 and allele B*82:01.
In allele B*15:01, allele B*18:01, allele B*35:01, allele B*46:01, allele B*53:01, allele B*57:01 and allele B*58:01.
In allele B*15:01, allele B*35:01, allele B*44:02, allele B*45:01, allele B*46:01, allele B*49:01, allele B*50:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*78:01 and allele B*82:01; requires 2 nucleotide substitutions.
In allele B*15:01, allele B*35:01, allele B*46:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*54:01, allele B*55:01, allele B*56:01, allele B*57:01, allele B*58:01, allele B*59:01 and allele B*78:01.
In allele B*18:01, allele B*27:01, allele B*27:05, allele B*37:01, allele B*40:01, allele B*40:02, allele B*41:01, allele B*45:01, allele B*49:01, allele B*50:01 and allele B*73:01.
In allele B*18:01, allele B*35:01, allele B*37:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*58:01 and allele B*78:01; requires 2 nucleotide substitutions.
In allele B*27:01, allele B*27:05 and allele B*47:01.
In allele B*27:01, allele B*27:05 and allele B*73:01.
In allele B*27:01, allele B*27:05, allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*49:01 and allele B*50:01.
In allele B*27:01, allele B*27:05, allele B*44:02 and allele B*47:01.
In allele B*27:05, allele B*37:01 and allele B*47:01; requires 2 nucleotide substitutions.
In allele B*35:01, allele B*37:01, allele B*44:02, allele B*53:01, allele B*57:01 and allele B*58:01.
In allele B*35:01, allele B*44:02, allele B*53:01, allele B*57:01 and allele B*58:01.
In allele B*35:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*58:01 and allele B*78:01.
In allele B*38:01, allele B*39:02 and allele B*67:01.
In allele B*38:01, allele B*49:01, allele B*51:01, allele B*52:01, allele B*53:01, allele B*57:01 and allele B*59:01; part of Bw4 motif involved in the recognition of KIR3DL1.
In allele B*40:01, allele B*40:02, allele B*41:01, allele B*44:02, allele B*45:01, allele B*47:01, allele B*49:01 and allele B*50:01.
In allele B*40:01, allele B*48:01 and allele B*81:01.
In allele B*44:02, allele B*45:01 and allele B*82:01.
In allele B*46:01; requires 2 nucleotide substitutions.
In allele B*57:01 and allele B*58:01; requires 2 nucleotide substitutions.
In allele B*57:01; requires 2 nucleotide substitutions.
In allele B*73:01; requires 2 nucleotide substitutions.
Heart- and neural crest derivatives-expressed protein 2
In COXPD35; reduced tRNA dimethylallyltransferase activity.
In COXPD35; unknown pathological significance.
Interaction with isopentenylpyrophosphate transferase
Abolishes interaction with GCK. Abolishes inhibition of GCK.
Associated with high triglyceride levels and low fasting plasma glucose levels; associated with a reduced risk for type 2 diabetes; the mutant protein is less efficiently regulated by physiological concentrations of fructose-6 phosphate.
3000-fold reduction in activity; abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA.
Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA.
In SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA.
In autosomal recessive or sporadic spinocerebellar ataxia affected Japanese individuals.
Reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA.
Reduces the activity to nearly undetectable levels.
Slightly reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA.
In PPH2; affects SMAD-mediated signaling.
Mothers against decapentaplegic homolog 9
AT-rich interactive domain-containing protein 5B
Abolishes methylation and FSK-dependent DNA-binding of the PHF2-ARID5B complex to promoters.
In EXT1; loss of activity; still able to form an oligomeric complex.
In isolated osteochondroma; somatic mutation.
No effect on heparan-sulfate biosynthesis.
In CMTX6; gain of function; results in a 5-fold increase in kinase activity, decreased sensitivity to pyruvate inhibition, reduced affinity for nucleotides and increased affinity for pyruvate dehydrogenase complex component E2 (PDC-E2), leading to PDC hyperphosphorylation and increased inactivation.
No effect on kinase activity; when associated with H-120.
No effect on kinase activity; when associated with N-121.
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial
Loss of abiity to promote megakaryocyte differentiation, enhance ERK and JNK signaling and up-regulate the expression of FLI1.
Developmentally-regulated GTP-binding protein 1
In isoform 2, isoform 3, isoform 4, isoform 5, isoform 8, isoform 9, isoform 10 and isoform 12.
In isoform 3, isoform 4, isoform 5, isoform 10 and isoform 12.
Sorbin and SH3 domain-containing protein 2
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3
Testis-specific Y-encoded-like protein 5
Affects transport of GPI-anchor proteins.
Abolishes aldosterone binding and transcription transactivation.
Abolishes steroid binding and transcription transactivation.
Decreased mineralocorticoid receptor activity.
Decreases aldosterone-binding and cortisol-binding.
In EOHSEP; alters receptor specificity and leads to constitutive activation.
In PHA1A; abolishes transcription transactivation upon aldosterone binding.
In PHA1A; abolishes translocation to the nucleus and transcription transactivation upon aldosterone binding.
In PHA1A; loss of aldosterone binding and transcription transactivation.
In PHA1A; reduces affinity for aldosterone and transcription transactivation.
In PHA1A; reduces transcription transactivation upon aldosterone binding.
Reduces aldosterone binding and abolishes transcription transactivation.
Reduces aldosterone binding and transcription transactivation.
Slightly reduces aldosterone binding and abolishes transcription transactivation.
Slightly reduces aldosterone binding and transcription transactivation.
Strong decrease of transcription transactivation.
Strongly decreases affinity for aldosterone and transcription transactivation.
Variant of uncertain significance; changed mineralocorticoid receptor activity; changed response curve to aldosterone stimulation.
H/ACA ribonucleoprotein complex subunit 1
G-protein coupled receptors family 2 profile 1
Vasoactive intestinal polypeptide receptor 1
In CDSP; carnitine transport is reduced to less than 1% of normal.
In CDSP; carnitine transport is reduced to less than 5% of normal.
In CDSP; carnitine transport reduced to 1% of wild-type.
In CDSP; carnitine transport reduced to 2% of wild-type.
In CDSP; carnitine transport reduced to 20% of wild-type.
In CDSP; carnitine transport reduced to less than 1% of wild-type.
In CDSP; carnitine transport reduced to less than 10% of wild-type.
In CDSP; carnitine transport reduced to less than 2% of wild-type.
In CDSP; carnitine transport reduced to less than 20% of wild-type.
In CDSP; carnitine transport reduced to less than 5% of wild-type.
In CDSP; carnitine transport reduced to less than 6% of wild-type.
In CDSP; loss of carnitine transport but stimulated organic cation transport; no effect on protein expression.
In CDSP; markedly reduced carnitine transport compared to the wild-type protein; less than 1% of wild-type activity.
In CDSP; may affect splicing; unknown pathological significance; reduces carnitine transport but the mutant retains 30% of wild-type activity.
In CDSP; reduces carnitine transport to 5% of wild-type activity.
In CDSP; reduces carnitine transport to 5% of wild-type.
In CDSP; reduces carnitine transport to less than 1% of normal.
In CDSP; reduces carnitine transport to less than 1% of wild-type activity.
In CDSP; reduces carnitine transport to less than 1% of wild-type.
In CDSP; reduces carnitine transport to less than 10% of wild-type activity.
In CDSP; reduces carnitine transport to less than 10% of wild-type.
In CDSP; reduces carnitine transport to less than 2% of wild-type activity.
In CDSP; reduces carnitine transport to less than 2% of wild-type.
In CDSP; reduces carnitine transport to less than 20% of wild-type activity.
In CDSP; reduces carnitine transport to less than 20% of wild-type.
In CDSP; reduces carnitine transport to less than 5% of wild-type activity.
In CDSP; reduces carnitine transport to less than 5% of wild-type.
In CDSP; reduces carnitine transport to less-than-1% to 3% of wild-type activity.
In CDSP; requires 2 nucleotide substitutions; reduces carnitine transport to less than 20% of wild-type activity.
In CDSP; unknown pathological significance; no effect on carnitine transport.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains 30% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains 50% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains 60% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains 70% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains more than 25% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains more than 30% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains more than 40% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport but the mutant retains more than 60% of wild-type activity.
In CDSP; unknown pathological significance; reduces carnitine transport to 40% of wild-type.
In CDSP; unknown pathological significance; reduces carnitine transport to less than 20% of wild-type.
Loss of both carnitine and organic cation transport functionalities. No effect on protein expression.
Reduces carnitine transport but the mutant retains more than 20% of wild-type activity.
Reduces carnitine transport but the mutant retains more than 60% of wild-type activity.
Reduces expression to 50%. No effect on carnitine transporter activity.
Tumor necrosis factor receptor superfamily member 27
Basic helix-loop-helix domain-containing protein USF3
Rare variant; may be a risk factor for epithelial thyroid carcinoma; results in increased epithelial-mesenchimal transition when coexpressed with 1470-Q--Q-1472 del.
Rare variant; may be a risk factor for epithelial thyroid carcinoma; results in increased epithelial-mesenchimal transition when coexpressed with Q-1472 del.
In PARK19B; patient fibroblasts show decreased levels of the protein.
Putative tyrosine-protein phosphatase auxilin
Associated with diabetes mellitus type-II; Los-Angeles.
In HPRI; impairs post-translational cleavage.
In MODY10; reduces binding affinity to INSR; reduces biological activity; reduces folding properties.
In PNDM4; uncertain pathological significance.
In MAAID; decreased maleylacetoacetate isomerase activity.
Peroxisomal carnitine O-octanoyltransferase
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.
Nuclear envelope integral membrane protein 2
In isoform 2, isoform 3, isoform 5, isoform 6 and isoform 7.
Protein tyrosine phosphatase domain-containing protein 1
Strongly reduced riboflavin transport; when associated with A-388 and A-395.
Strongly reduced riboflavin transport; when associated with A-388 and A-487.
Strongly reduced riboflavin transport; when associated with A-395 and A-487.
Loss of function in NuRD complex recruitment to telomeric regions.
RRK motif; mediates NuRD recruitment to telomeres
Abolishes enzyme activity but does not affect stability of the protein.
Induces a strong decrease in enzyme activity but has no effect on stability of the protein. Unstable protein; when associated with S-205 and S-223.
Induces a strong decrease in enzyme activity has no effect on stability of the protein.
Induces a weak decrease in enzyme activity but has no effect on stability of the protein. Unstable protein; when associated with S-205 and S-321.
Induces a weak decrease in enzyme activity but has no effect on stability of the protein. Unstable protein; when associated with S-223 and S-321.
Found in a child with sporadic epilepsy; unknown pathological significance.
Rho guanine nucleotide exchange factor 15
Eukaryotic translation initiation factor 4B
Non-phosphorylatable mutant whose expression results in reduced SLC4A7 protein levels in TSC2-deficient cells accompanied by decrease in the bicarbonate-dependent flux into nucleotide synthesis.
Polypeptide N-acetylgalactosaminyltransferase 18
Serine/threonine-protein phosphatase 4 regulatory subunit 3B
Abolishes the interaction with CLTCL1/Clathrin.
Interaction with AP1G1, AP1G2, GGA1 and GGA3
Interchain (between SU and TM chains, or C-46 with C-439); in linked form
p21-activated protein kinase-interacting protein 1
Inhibits signaling via PRLR; mutant PRL acts as PRLR antagonist.
Probable disease-associated variant found in a patient with intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus and congenital diaphragmatic hernia.
Probable disease-associated variant found in a patient with severe intellectual disease, microcephaly and feeding difficulties as well as cerebral atrophy.
Mediates interaction with the PDZ domain of NOS1
Found in a patient with neurodevelopmental disorder with hypotonia, dysmorphic facies and skin abnormalities; unknown pathological significance.
In APIMmut; does not affect subcellular location.
Required for interaction with SLF1 and RAD18
SMC5-SMC6 complex localization factor protein 2
Neuronal acetylcholine receptor subunit alpha-4
Heparan sulfate glucosamine 3-O-sulfotransferase 6
In HAE8; unknown pathological significance.
In MDDGB14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type.
In MDDGC14; no change in protein abundance.
In MDDGC14; no change in protein abundance; shows an increased propensity to form punctate aggregates.
In MDDGC14; slight reduction in protein abundance.
In MDDGC14; slight reduction in protein abundance; shows an increased propensity to form punctate aggregates.
In MDDGC14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type.
Mannose-1-phosphate guanyltransferase beta
In DRS1; unknown pathological significance.
Important for determining product chain length
In EPM7; causes a dominant-negative loss of current upon membrane depolarization.
Potassium voltage-gated channel subfamily C member 1
Eukaryotic translation initiation factor 4 gamma 2
60-65% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane.
80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-581 and K-584.
80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-581 and K-585.
80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-584 and K-585.
85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with C-371.
85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with E-371.
85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-74.
90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with E-590.
90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-583.
Associated with a decreased severity of CAD.
Associated with higher plasma cholesterol.
Associated with increased plasma HDL cholesterol.
Associated with premature coronary heart disease.
Associated with reduced plasma HDL cholesterol.
Could be associated with reduced plasma HDL cholesterol.
Decreased palmitoylation; when associated with S-3, S-23 and S-1110.
Decreased palmitoylation; when associated with S-3, S-23 and S-1111.
Highly decreased protein abundance. Highly decreased ATPase activity. Highly decreased phospholipid translocase activity.
In FHA1; deficient cellular cholesterol efflux.
In FHA1; loss of localization to plasma membrane; decreased cholesterol efflux; decreased phospholipid efflux.
In FHA1; moderately decreased protein abundance; does not affect ATPase activity; moderately decreased phospholipid translocase activity.
In FHA1; uncertain pathological significance.
In Scott syndrome; shows impaired trafficking of the mutant protein to the plasma membrane.
In TGD; deficient cellular cholesterol efflux.
In TGD; highly decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; loss protein subcellular localization to the plasma membrane.
In TGD; loss of interaction with APOE; unable to generate APOE-containing high density lipoproteins; moderately decreased protein abundance; moderately decreased ATPase activity; moderately decreased phospholipid translocase activity.
In TGD; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity.
In TGD; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; loss protein subcellular localization to the plasma membrane.
In TGD; the mutant protein is retained in the endoplasmic reticulum while the wild-type protein is located at the plasma membrane.
Inhibits ATPase activity; when associated with M-1952. Decreases translocase activity; when associated with M-1952. Does not affect protein subcellular localization in plasma membrane and endosome; when associated with M-1952.
Inhibits ATPase activity; when associated with M-939. Decreases translocase activity; when associated with M-939. Does not affect protein subcellular localization in plasma membrane and endosome; when associated with M-939.
May be associated with increased risk of ischemic heart disease.
Mild decrease of palmitoylation. Loss of localization to plasma membrane. Decreased cholesterol efflux. Decreased phospholipid efflux. Decreased palmitoylation; when associated with S-23, S-1110 and S-1111.
Mild decrease of palmitoylation. Loss of localization to plasma membrane. Decreased palmitoylation; when associated with S-3, S-1110 and S-1111.
Moderately decreased protein abundance. Does not affect ATPase activity. Moderately decreased phospholipid translocase activity.
Moderately decreased protein abundance. Highly decreased ATPase activity. Highly decreased phospholipid translocase activity.
No effect on phospholipid and cholesterol efflux and on localization to cell membrane.
No effect on phospholipid and cholesterol efflux or localization to cell membrane. 85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with C-74 or C-375.
No effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with C-304.
No effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with C-308.
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.
Chromatin accessibility complex protein 1
Strongly reduces affinity for glycopeptide substrates. Nearly abolishes enzyme activity.
In LNCR; unknown pathological significance.
Abolished Cys methylation and ability to bind 'Lys-63'-linked ubiquitin.
Disrupted zinc-finger; abolished methylation at C-673.
Found in an patient with a form of frontometaphyseal dysplasia; unknown pathological significance.
Loss of TRIM60-mediated SUMOylation; when associated with R-329.
Loss of TRIM60-mediated SUMOylation; when associated with R-562.
TGF-beta-activated kinase 1 and MAP3K7-binding protein 2
Leucine-rich repeat-containing protein 26
Found in a patient with intellectual disability, frontal epilepsy and mild facial dysmorphism.
Rap guanine nucleotide exchange factor 1
Does not affect hydrogen peroxide transport activity under stress condition.
Does not affect hydrogen peroxide transport under stress condition.
Does not affect loss of hydrogen peroxide transport after stress.
Loss of hydrogen peroxide transport activity under stress condition.
Loss of hydrogen peroxide transporter activity.
Slightly affect hydrogen peroxide transport after stress.
Ganglioside-induced differentiation-associated protein 1-like 1
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.
Tumor necrosis factor receptor superfamily member 10B
Heterodimer with truncated apolipoprotein A-II.
Homodimer, with 1 methionine sulfoxide, oxidation at Met-49.
Homodimer, without methionine sulfoxide.
Interchain (with C-136 in APOD); in heterodimeric form
In POF6; one individual with premature ovarian failure.
In DFNB108; impairs plasma membrane location; abolishes downstream NFkB activation.
In a renal clear cell carcinoma sample; somatic mutation.
Inactive tyrosine-protein kinase transmembrane receptor ROR1
Hairy/enhancer-of-split related with YRPW motif protein 1
Transcriptional repression and interaction with NCOR1 and SIN3A
Serine/threonine-protein phosphatase 6 regulatory subunit 1
Abolishes autophosphorylation. Abolishes interaction with SRC.
Loss of phosphorylation site. Strongly reduced interaction with GRB2.
Dominant-negative mutant. Impairs pre-mRNA splicing activity. Fails to interact with any of viral RNA forms.
In NMOAS; unknown pathological significance.
Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16
Abolished ubiquitination by the DCX(AMBRA1) complex.
Abolishes in vitro cleavage by CASP3 and CASP8; when associated with A-133.
Abolishes in vitro cleavage by CASP3 and CASP8; when associated with A-149.
Abolishes in vitro cleavage by CASP8; when associated with A-133.
Abolishes in vitro cleavage by CASP8; when associated with A-146.
Complete loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-93.
Decreases K48 polyubiquitination and stabilizes BECN1.
Decreases interaction with BCL2L1 isoform Bcl-X(L).
Decreases interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L).
Does not affect ubiquitination by the DCX(AMBRA1) complex.
Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)
No effect on interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L).
Partial loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-90.
Weakly decreases interaction with MUHV-4 M11, disrupts interaction with BCL2 and decreases interaction with BCL2L1 isoform Bcl-X(L). Reduces interaction with BCL2L10.
Weakly decreases interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L).
Weakly decreases interaction with MUHV-4 M11, greatly decreases interaction with BCL2L1 isoform Bcl-X(L).
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.
Required for nuclear retention and interaction with LMNA isoform C
Breakpoint for translocation to form CHIC2-ETV6 in AML
Breakpoint for translocation to form ETV6-AML1 in ALL
Breakpoint for translocation to form ETV6-MDS2 in MDS
Breakpoint for translocation to form PAX5-ETV6
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.
Breakpoint for translocation to form TPR-MET oncogene
Complete loss of kinase activity and of ligand-induced ubiquitination. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1235.
Complete loss of kinase activity. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1234.
Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation.
Found in lung cancer also including cases carrying EGFR mutations; unknown pathological significance; decreased hepatocyte growth factor-activated receptor activity; decreased interaction with HGF.
In DA11; not phosphorylated in reponse to HGF; severely decreased tyrosin kinase activity.
In OSFD; loss of CBL-mediated destabilization.
In RCCP; causes malignant transformation in cell lines.
In RCCP; constitutive autophosphorylation.
In RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines.
In gastric cancer; prolonged tyrosine phosphorylation in response to HGF/SF; transforming activity in athymic nude mice.
No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1356.
No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1365.
No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1356 and F-1365.
No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1349, F-1356 and F-1365.
Probable disease-associated variant found in lesional sample from a patient with sporadically occurring, unilateral osteofibrous dysplasia; somatic mutation; complete loss of ligand-induced CBL-mediated ubiquitination, resulting in protein stabilization.
Required for ligand-induced CBL-mediated ubiquitination
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
U4/U6.U5 small nuclear ribonucleoprotein 27 kDa protein
U4/U6.U5 small nuclear ribonucleoprotein 27kDa protein
In LGMDR1; unknown pathological significance.
Loss of activity. No effect on CMYA5-binding. Does not degradate p53/TP53.
In FHL5; leads to a complete loss of the ability to interact with STX11.
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.
CAP-Gly domain-containing linker protein 4
In NEDGTH; unknown pathological significance; contrary to the wild type, it fails to rescue eye defects in Rpt2-null Drosophila.
Heterogeneous nuclear ribonucleoprotein C-like 3
Heterogeneous nuclear ribonucleoprotein C-like 4
Chromodomain-helicase-DNA-binding protein 6
Required for DNA-dependent ATPase activity
Increases calcium-independent actin-severing activity.
In DEDBANP; decreased G protein-coupled receptor signaling.
In DEDBANP; decreased G protein-coupled receptor signaling; decreased cell surface localization.
In DEDBANP; loss of protein expression; loss of G protein-coupled receptor signaling.
In DEDBANP; unknown pathological significance.
Embryonic polyadenylate-binding protein 2
Complete loss of ATPase and RNA-unwinding activities. Loss of HIV-1 mRNA nuclear export. Does not promote the translation of HIV-1 RNA. No effect on IFNB1 induction. No effect on RNA-binding. Loss of inhibition of NF-kappa-B-mediated transcriptional activity.
Does not promote the translation of HIV-1 RNA. No effect on general translation; when associated with A-200; A-230: A-347 and A-348.
Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-183 and A-240.
Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-183 and A-269.
Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-181; A-240 and A-269.
Greatly impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFNB1 induction; when associated with A-183; A-240 and A-269.
Impaired interaction with EIF4E; decreased repression of cap-dependent translation. Fails to induce stress granule assembly and to rescue cell viability after stress. No effect on translation of HIV-1 RNA; when associated with A-38.
Impaired interaction with EIF4E; impaired stress granule formation, decreased repression of cap-dependent translation and decreased ability to enhance IRES-mediated translation. No effect on translation of HIV-1 RNA; when associated with A-43.
Impairs nuclear export and interaction with XPO1/CMR1.
Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-442 and A-456.
Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-442 and A-520.
Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-438; A-456 and A-520.
Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-429; A-442; A-456 and A-520.
Impairs phosphorylation by TBK1 and fails to synergize with TBK1 in IFN-beta induction; when associated with A-438; A-442; A-456 and A-520.
In MRXSSB; also found as a somatic mutation in medulloblastoma; loss of ATPase activity; increased interaction with CSNK1E in the absence of dsRNA; contrary to wild-type protein, strongly interacts with CSNK1A1 and CSNK1D in vivo; strongly increased ability to activate CSNK1E kinase activity, leading to increased DVL phosphorylation, thereby activating Wnt/beta-catenin signaling; increased RNA-binding; no effect on subcellular location.
In MRXSSB; loss-of-function mutation affecting regulation of Wnt signaling.
In medulloblastoma; somatic mutation; loss of ATPase activity; interacts with CSNK1E, even in the presence of dsRNA; contrary to wild-type protein, strongly interacts with CSNK1A1 and CSNK1D in vivo; strongly increased ability to activate CSNK1E kinase activity, leading to increased DVL phosphorylation, thereby activating Wnt/beta-catenin signaling; no effect on RNA-binding, nor on subcellular location.
Increased NF-kappa-B-mediated transcriptional activity, contrary to wild-type which is inhibitory in this experimental setting.
Interacts with IRF3 and enhances IFNB promoter induction.
Involved in stimulation of ATPase activity by DNA and RNA, nucleic acid binding and unwinding and HIV-1 replication
Loss of RNA helicase, but not ATPase activity; no effect on the repression of cap- and IRES-dependent translation, WNT/beta catenin signaling, up-regulation of CDKN1A promoter activity, HNF4A-mediated MTTP transcriptional activation, nor on stress granule assembly.
Loss of both ATPase and RNA helicase activities; decreased up-regulation of CDKN1A promoter activity and HNF4A-mediated MTTP transcriptional activation; no effect on the repression of cap- and IRES-dependent translation, WNT/beta catenin signaling, nor on stress granule assembly. Does not promote the translation of HIV-1 RNA.
Loss of interaction with TRAF3, reduced TRAF3 'K-63'-linked autoubiquitination.
Loss of interaction with VACV protein K7, IRF3 activation and IFNB1 promoter induction.
No effect on general translation; when associated with A-200; A-207; A-230 and A-347.
No effect on general translation; when associated with A-200; A-207; A-230 and A-348.
No effect on general translation; when associated with A-200; A-207; A-347 and A-348.
No effect on general translation; when associated with A-207; A-230; A-347 and A-348.
Phosphoserine; by CSNK1E and TBK1; in vitro
Reduces total phosphorylation by 30%. Abolishes interaction with IRF3 and fails to enhance IFNB promoter induction. No effect on interaction with IKBKE.
Reduces total phosphorylation by 50%. No effect on interaction with IKBKE.
Reduces total phosphorylation by 60%. No effect on interaction with IKBKE.
Required for TBK1 and IKBKE-dependent IFNB1 activation
Strong decrease in ATPase activity and RNA-unwinding activity. Does not promote the translation of mRNAs containing long structured 5'UTRs, including that of CCNE1. No effect on the translation of HIV-1 RNA.
Class A basic helix-loop-helix protein 15
Mitochondrial import inner membrane translocase subunit Tim21
TLR4 interactor with leucine rich repeats
In PEERB; altered intracellular trafficking from the ER to the Golgi to the plasma membrane.
Trafficking protein particle complex subunit 2-like protein
Coiled-coil domain-containing protein 14
Coiled-coil domain-containing protein 86
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
Abolishes endoplasmic reticulum localization.
Abolishes activity. Disrupts Golgi structure.
Loss of phosphorylation. No effect on binding of GDI1 and GDI2.
Phosphomimetic mutant. Loss of binding to GDI1, GDI2, CHM and CHML.
In IMD72; loss of function; T-cells display excessive degranulation and granule release; no effect on protein levels in T-cells, nor on interaction with WASF2; when tested in a heterologous system, formed WAVE complexes that poorly interact with ARF1 and could not promote F-actin polymerization upon stimulation with an ARF1-RAC1 dimer; no effect on interaction with RICTOR.
In IMD72; loss of function; decreased protein levels in T-cells; T-cells display excessive degranulation and granule release.
In IMD72; loss of function; decreased protein levels in T-cells; decreased interaction with WASF2 and poor formation of WAVE2 complex.
In IMD72; loss of function; decreased protein levels in T-cells; decreased interaction with WASF2 and poor formation of WAVE2 complex; T-cells display excessive degranulation and granule release; cells exhibit reduced cortical F-actin and aberrant membrane spikes and WAS-mediated puncta, defective cell spreading and lamellipodia and reduced migratory velocity, as well as abnormal activation, blunted proliferation, decreased IL2 and TNF production and defective TCR-induced phosphorylation of mTORC2 complex substrate AKT; homozygous patient neutrophils migrating in chemokine gradients exhibit reduced velocity and directional persistence, unusual elongation and misdirected competing leading edges; no effect on interaction with RICTOR.
Decreased amplitudes of swelling-activated current.
Volume-regulated anion channel subunit LRRC8C
In AHUS3 and ARMD13; the mutant is both expressed and secreted at lower levels than wild-type protein; mediates C3 degradation to a lesser extent than that of controls.
Long-chain-fatty-acid--CoA ligase ACSBG1
In MDDGA10; abolishes xylosyltransferase activity.
In MDDGA10; unknown pathological significance; loss of binding activity of alpha-dystroglycan (DAG1) for the ligand laminin in fibroblasts from patients; loss of alpha-dystroglycan functional glycosylation in fibroblasts from patients; does not affect Golgi apparatus localization.
Ribitol-5-phosphate xylosyltransferase 1
Abolished phosphorylation, leading to increased interaction with CLSTN1.
Mimics CLSTN1, leading to decreased interaction with CLSTN1.
No effect on motor function; when associated with A/D-521.
No effect on motor function; when associated with A/D-524.
Sterile alpha motif domain-containing protein 7
Abolishes calcium binding via the EF-hand.
Abolishes increased channel activity due to a gain of function mutation; when associated with P-604.
Abolishes increased channel opening in response to cAMP and phosphorylation by PKA.
Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-860 and A-863.
Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-860 and A-867.
Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-863 and A-867.
Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-860; A-863 and A-867.
Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-849; A-860; A-863 and A-867.
Abolishes oligomerization and interaction with PKD1; when associated with A-846; A-849; A-860; A-863 and A-867.
Abolishes phosphorylation of the N-terminal domain. Abolishes the ability to complement a pkd2-deficient zebrafish mutant; when associated with A-80.
Decreases interaction with PACS1 and enhances expression at the cell membrane. Decreases phosphorylation; when associated with A-721; A-801; A-831 and A-943.
Decreases phosphorylation of the N-terminal domain. Abolishes the ability to complement a pkd2-deficient zebrafish mutant; when associated with A-76.
Decreases phosphorylation; when associated with A-721; A-801; A-812 and A-831.
Decreases phosphorylation; when associated with A-721; A-801; A-812 and A-943.
Decreases phosphorylation; when associated with A-721; A-812; A-831 and A-943.
Decreases phosphorylation; when associated with A-801; A-812; A-831 and A-943.
Gain-of-function mutation resulting in increased channel activity. Absence of gain of function; when associated with F-605 DEL; when associated with A-201; when associated with V-511; when associated with G-414; when associated with G-420; when associated with Y-684 DEL; when associated with A-684. Increased channel activity; when associated with 736-L-N-737 DEL.
Important for interaction with PACS1 and PACS2
In PKD2; affects channel activity as it is able to abolish channel currents induced by the gain-of-function artificial mutant P-604.
In PKD2; loss of function in the release of Ca(2+) stores from the endoplasmic reticulum; no effect on location at the endoplasmic reticulum; affects channel activity as it is able to abolish channel currents induced by the gain-of-function artificial mutant P-604.
In PKD2; somatic mutation; abolishes channel currents induced by the gain-of-function artificial mutant P-604.
Increased channel activity; when associated with P-604.
Loss of calcium-binding site; when associated with A-771.
Loss of calcium-binding site; when associated with A-774.
Loss of phosphorylation at this site. Impairs release of Ca(2+) stores from the endoplasmic reticulum.
Loss of protein solubility; when associated with K-849.
Phosphomimetic mutant. No effect on release of Ca(2+) stores from the endoplasmic reticulum.
Strongly decreases interaction with PACS1 and enhances expression at the cell membrane.
Strongly increases calcium binding affinity.
In USH4; loss of sulfatase activity toward p-nitrocatechol sulfate; loss of processing of the precursor protein suggesting impaired transport to lysosomes.
In CDG2N; loss of manganese ion transmembrane transport; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; no effect on protein abundance.
In CDG2N; no detectable serum or urinary manganese levels in an affected individual who also carries R-38 mutation.
No effect on protein abundance; decreased cadmium ion transmembrane transport; increased resistance to cadmium cytotoxicity; associated with decreased activity of manganese-dependent enzymes.
Probable disease-associated variant found in patients with Leigh-like syndrome; no effect on protein abundance; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; loss of manganese ion transmembrane transport.
Carnitine O-palmitoyltransferase 1, liver isoform
Carnitine O-palmitoyltransferase N-terminal
In PRLTS6; decreased protein abundance; reduced assembly of the mitochondrial ribosomal small subunit.
Abolishes ability to deubiquitinate histone H2A; when associated with 665-R. No decrease of total H2AK15ub levels following ionizing radiation; when associated with 665-R.
Abolishes ability to deubiquitinate histone H2A; when associated with 665-R. Suppresses ionizing radiation-induced H2AK13,15Ub; when associated with 372-R.
Ubiquitin carboxyl-terminal hydrolase 51
Found in patients with intellectual disability; unknown pathological significance.
In DEE18; alters splice sites and probably alternative splicing.
Mediates interaction with the GATOR1 complex
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.
Leucine zipper alpha helical coiled-coil region
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
Oxysterol-binding protein-related protein 1
In ASD4; gain of function in sequence-specific DNA binding transcription factor activity; gain of function in sequence-specific DNA binding transcription factor activity in the presence of cotranscription factors NKX2-5 and GATA4 or GATA5.
In ASD4; significant gain of function in sequence-specific DNA binding transcription factor activity; gain of function in sequence-specific DNA binding transcription factor activity in the presence of cotranscription factors NKX2-5 and GATA4 or GATA5.
NACHT, LRR and PYD domains-containing protein 8
Pre-rRNA-processing protein TSR2 homolog
Decreased interaction with CUL3, especially with the neddylated form of CUL3.
Decreased interaction with RBBP8 and complete loss of nuclear localization, found exclusively in the cytoplasm.
Decreased interaction with RBBP8 and increased DNA-end resection and homologous recombination frequency following DNA double-strand breaks compared to the wild-type protein. No significant change in subcellular location.
Impaired PPP2R5B-binding and proteasomal degradation.
Impaired homodimerization and PPP2R5B proteasomal degradation. No effect on PPP2R5B-binding.
No effect on PPP2R5B-binding, nor on homodimerization, but loss of CUL3 recruitment to the KLHL15/PPP2R5B complex and impaired PPP2R5B proteasomal degradation.
No effect on homodimerization, PPP2R5B-binding, nor on PPP2R5B proteasomal degradation.
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.
Necessary and sufficient for the interaction with SQSTM1
ATP-dependent Clp protease proteolytic subunit, mitochondrial
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.
Intraflagellar transport protein 22 homolog
Sperm protein associated with the nucleus on the X chromosome N2
31 X 5 AA repeats of C-C-[GRQVIL]-[SPTR]-[VSTQPC]
Found in a patient with age-related macular degeneration; unknown pathological significance.
Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-328.
Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-330.
Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-328 and E-330.
Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-324, E-328 and E-330.
Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-235, E-324, E-328 and E-330.
Enables homodimerization; when associated with A-280.
Enables homodimerization; when associated with A-383.
In EPM10; does not affect interaction with EPM2A and NHLRC1.
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.
Involved in ligand recognition and product release
In GPIBD18; almost complete loss of function; when tested in PIGS-knockout cells, mediates only very partial restoration of GPI-anchored protein expression at the cell surface; strong decrease in protein level, possibly due to nonsense-mediated mRNA decay.
In GPIBD18; partial loss of function; when tested in PIGS-knockout cells, mediates partial restoration of GPI-anchored protein expression at the cell surface.
In GPIBD18; unknown pathological significance.
No effect on function in GPI-anchor attachment to protein.
Interaction with NCK2 second and third SH3 domain (minor)
Interaction with NCK2 third SH3 domain (major)
Decreased methylation; when associated with K-94.
Decreased methylation; when associated with K-96.
Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ
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.
DDB1- and CUL4-associated factor 4-like protein 2
Ras-GEF domain-containing family member 1C
Guanine nucleotide-binding protein subunit alpha-12
Nucleolar and spindle-associated protein 1
Found in a patient with Gordon-Holmes syndrome; unknown pathological significance.
Found in a patient with sporadic ataxia and BNHS; unknown pathological significance.
Patatin-like phospholipase domain-containing protein 6
In HYPT13; dominant negative; decreased keratin intermediate filament formation.
Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1
Transcription cofactor vestigial-like protein 1
3 X 11 AA approximate tandem repeats; mediates binding and activation by anionic lipid vesicles
Abolishes formation of the interchain disulfide that can be observed when the enzyme is treated with copper phenanthrolene (in vitro).
Choline-phosphate cytidylyltransferase A
Complete loss of enzymatic activity and enzyme dimerization. No change in binding to 2-5A and RNA.
Complete loss of enzymatic activity. No change in 2-5A binding activity and enzyme dimerization.
Complete loss of enzymatic activity. No change in 2-5A binding and enzyme dimerization.
Reduced 2-5A binding activity; almost complete loss of 2-5A binding activity; when associated with N-240.
Reduced 2-5A binding activity; almost complete loss of 2-5A binding activity; when associated with N-274.
Risk factor for prostate cancer; reduced enzymatic 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.
Iroquois-class homeodomain protein IRX-4
Important for binding with the scorpion mesomartoxin; when the scorpion mesomartoxin-rKv1.2/KCNA2 interaction is modeled, this residue is close to the 'Y-57' residue of the toxin
Important for normal, slow channel gating
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.
Vacuolar protein sorting-associated protein 28 homolog
Abolishes ADGRL3 binding; when associated with A-38; A-43 and A-45.
Abolishes ADGRL3 binding; when associated with A-38; A-43 and A-47.
Abolishes ADGRL3 binding; when associated with A-43.
Abolishes ADGRL3 binding; when associated with A-43; A-45 and A-47.
Abolishes ADGRL3 binding; when associated with A-64. Abolishes ADGRL3 binding; when associated with A-38; A-43 and A-47.
Abolishes ADGRL3 binding; when associated with A-89.
Abolishes ADGRL3 binding; when associated with A-91.
Adds a glycosylation site that strongly reduces homodimerization; when associated with T-183.
In HH21; rare variant associated with susceptibility to disease; patients have a second mutation in another HH-associated gene including FGFR1, HS6ST1 and FGF17.
In HH21; rare variant associated with susceptibility to disease; the patient has a second mutation in the HH-associated gene FGFR1.
Leucine-rich repeat transmembrane protein FLRT3
No effect on homodimerization; when associated with A-181.
No effect on homodimerization; when associated with A-183.
Abolishes ability to promote guanylylation of RTCB.
Inhibits the transcriptional activity of RELA and attenuates NF-kappa-B-mediated gene expression.
Necessary for interaction with replicase polyprotein 1ab nsp14 of IBV
Disruption of membrane localization and impaired interaction with CK2. Loss of phospholipid binding; when associated with C-42. Loss of phospholipid binding; when associated with C-44. Disruption of membrane localization, loss of phospholipid binding and impaired interaction with CK2; when associated with C-42 and C-44.
Great loss of binding to capping proteins; when associated with A-155 and A-157.
Interaction with ATM, CKIP, IFP35 and NMI
No change in cell morphology and actin cytoskeleton. Great loss of binding to capping proteins and no change in cell morphology and actin cytoskeleton; when associated with E-155.
No change in cell morphology and actin cytoskeleton. Great loss of binding to capping proteins and no change in cell morphology and actin cytoskeleton; when associated with E-157.
No change in cell morphology and actin cytoskeleton. Great loss of binding to capping proteins; when associated with A-155. Great loss of binding to capping proteins; when associated with A-155 and A-159.
No change in cell morphology and actin cytoskeleton. Great loss of binding to capping proteins; when associated with A-157. Great loss of binding to capping proteins; when associated with A-157 and A-159.
No effect on binding to capping proteins and loss of phospholipid binding; when associated with A-135 and A-137.
No effect on binding to capping proteins; when associated with A-133 and A-135.
No effect on binding to capping proteins; when associated with A-133 and A-137.
No effect on binding to capping proteins; when associated with E-133.
No effect on binding to capping proteins; when associated with E-135.
No effect on subcellular localization. No effect on subcellular localization; when associated with C-42. Disruption of membrane localization, loss of phospholipid binding and impaired interaction with CK2; when associated with W-123. Disruption of membrane localization, loss of phospholipid binding and impaired interaction with CK2; when associated with C-42 and W-123.
No effect on subcellular localization. No effect on subcellular localization; when associated with C-44. Disruption of membrane localization, loss of phospholipid binding and impaired interaction with CK2; when associated with W-123. Disruption of membrane localization, loss of phospholipid binding and impaired interaction with CK2; when associated with C-44 and W-123.
Pleckstrin homology domain-containing family O member 1
Abolishes ability to stimulate p53/TP53 ubiquitination. No effect on nuclear localization in response to DNA damage.
Abolishes interaction with the RPA complex and subsequent recruitment at DNA damage sites.
Decreased interaction with RAD51; when associated with 36-A--A-38 and 53-A--A-55.
Decreased interaction with RAD51; when associated with 36-A--A-38 and 70-A--A-72.
Decreased interaction with RAD51; when associated with 53-A--A-55 and 70-A--A-72.
Does not affect interaction with the RPA complex and subsequent recruitment at DNA damage sites.
In FANCW; abolishes interaction with the RPA complex and subsequent recruitment of the protein at DNA damage sites; decreased function in double-strand break repair via homologous recombination.
Markedly decreases phosphorylation following ionizing radiation and abolishes ability to stimulate p53/TP53 ubiquitination; when associated with A-46.
Markedly decreases phosphorylation following ionizing radiation and abolishes ability to stimulate p53/TP53 ubiquitination; when associated with A-63.
In a lung bronchoalveolar carcinoma sample; somatic mutation.
tRNA-splicing endonuclease subunit Sen34
Abolishes homodimerization; when associated with A-132 and A-221.
Abolishes homodimerization; when associated with A-132 and A-225.
Abolishes homodimerization; when associated with A-221 and A-225.
Abolishes interaction with CHMP1A, CHMP1B and CHMP2A.
Abolishes interaction with CHMP1A, CHMP1B and CHMP2A. Abolishes location at the midbody.
Important for association with membranes
Strongly reduces binding to membranes; when associated with E-168 and E-231.
Strongly reduces binding to membranes; when associated with E-221 and E-220.
Strongly reduces binding to membranes; when associated with E-221 and E-231.
116 kDa U5 small nuclear ribonucleoprotein component
2 fold decreased affinity and catalytic activity for cGMP. 8 fold decreased catalytic activity for cAMP without affecting the affinity for cAMP.
Completely abolishes catalytic activity.
Decreased affinity and catalytic activity for cGMP and cAMP.
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
In isoform PDE9A2, isoform PDE9A3, isoform PDE9A6, isoform PDE9A9 and isoform PDE9A21.
In isoform PDE9A6, isoform PDE9A12 and isoform PDE9A17.
Induces a 2 fold change in inhibitory sensitivity by BAY-73-9961.
Induces a 6-9 fold change in inhibitory sensitivity by BAY-73-9961.
Induces a dramatic change in inhibitory sensitivity by BAY-73-9961.
Reduces catalytic activity, but has no effect on substrate affinity.
Cation-dependent mannose-6-phosphate receptor
Abolishes transferase activity; when associated with A-570.
Abolishes transferase activity; when associated with A-571.
Protein interaction domain; mediates interaction with DNA polymerase zeta
Inhibits phosphorylation and interaction with plasmodium berghei 14-3-3 protein; when associated with A-124 and A-333.
Reduces F-actin bundling but not F-actin binding activity.
Reduces interaction with plasmodium berghei 14-3-3 protein. Inhibits phosphorylation and interaction with plasmodium berghei 14-3-3 protein; when associated with A-124 and A-403.
Reduces interaction with plasmodium berghei 14-3-3 protein. Inhibits phosphorylation and interaction with plasmodium berghei 14-3-3 protein; when associated with A-333 and A-403.
Zinc finger and BTB domain-containing protein 21
Complete loss of type I receptor binding.
BTB/POZ domain-containing protein KCTD12
In DFNA85; unknown pathological significance; decreased deubiquitinase activity.
In DFNA85; unknown pathological significance; requires 2 nucleotide substitutions; decreased deubiquitinase activity.
Ubiquitin carboxyl-terminal hydrolase 48
In EVR1; 48% loss of its wild-type activity; associated in a EVR4 patient with mutation Cys-444 in LPR5.
In EVR1; minor reduction of its wild-type activity.
In EVR1; reduced signaling activity in presence of WNT3A but no change in presence of NDP/norrin.
Increased signaling activity in presence of NDP/norrin but not in presence of WNT3A.
Increased signaling activity in presence of WNT3A but not in presence of NDP/norrin.
Reduced signaling activity in presence of NDP/norrin.
Slightly increased signaling activity in presence of NDP/norrin and reduced signaling in presence of WNT3A.
Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-28 and A-119.
Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-28 and A-68.
Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-68 and A-119.
Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-28; A-68 and A-119.
Strongly reduced phosphorylation by DYRK2; when associated with A-26; A-28; A-68 and A-119.
RecQ-mediated genome instability protein 1
Inhibits nuclear localization and alternative splicing activity.
Necessary for alternative splicing activity
Nuclear speckle splicing regulatory protein 1
Nuclear speckle splicing regulatory protein 1 N-terminal
Nuclear speckle splicing regulatory protein 1 RS-like
Abolishes reducing activity, does not affect dimerization. Abolishes reducing activity; when associated with S-72.
Abolishes reducing activity, does not affect dimerization. Abolishes reducing activity; when associated with S-75.
Gamma-interferon-inducible lysosomal thiol reductase
SH3 domain-binding glutamic acid-rich-like protein 2
Loss of plasmanylethanolamine desaturase activity.
No effect on desaturase plasmanylethanolamine activity.
No effect on plasmanylethanolamine desaturase activity.
Ubiquitin-conjugating enzyme E2 variant 1
5.4-fold decrease in activity with p-nitrophenyl acetate as substrate; no change in affinity for p-nitrophenyl acetate; loss of activity with L- or D-methylphenidate as substrate.
Dual specificity tyrosine-phosphorylation-regulated kinase 4
Leucine-rich repeat and IQ domain-containing protein 4
Receptor-type tyrosine-protein phosphatase F
Found in a patient with congenital hyperinsulinism; markedly decreases transporter activity.
Abolishes interaction with microcystin toxin.
Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
(E3-independent) E2 ubiquitin-conjugating enzyme
In FRTS2; loss of function in the homozygous state; loss of localization to cell membrane.
In HCINF2; loss of phosphate transport activity; loss of localization to apical plasma membrane; a complete intracellular retention and no detectable actin colocalization.
In HCINF2; loss of phosphate transport activity; loss of localization to apical plasma membrane; display a complete intracellular retention and no detectable actin colocalization.
In HCINF2; no change in phosphate transport activity; changed localization to the apical plasma membrane; partial retention inside the cell.
In NPHLOP1; causes hypophosphatemic osteoporosis; results in lower phosphate current, decreases affinity for phosphate and decreases phosphate uptake compared to wild-type; shows a dominant-negative effect.
In NPHLOP1; causes hypophosphatemic urolithiasis; requires 2 nucleotide substitutions; results in lower phosphate current, decreases affinity for phosphate and decreases phosphate uptake compared to wild-type; shows a dominant-negative effect.
Sodium-dependent phosphate transport protein 2A
Unable to reach the cell surface upon transfection.
Required for nuclear speckle localization
HLA class II histocompatibility antigen, DO beta chain
In CAVIPMR; unknown pathological significance.
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.
Interaction with VPS4A, VTA1, MITD1 STAMBP and USP8
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 autosomal recessive retinitis pigmentosa.
In SVD; overexpression produces a non-selective cation current that depolarizes transfected cells and increases their fragility.
In an ovarian clear cell carcinoma sample; somatic mutation.
Serine/threonine-protein kinase 3 20kDa subunit
Serine/threonine-protein kinase 3 36kDa subunit
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.
Potassium voltage-gated channel subfamily G member 1
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
Required for nuclear localization (NLS1)
Required for nuclear localization (NLS2)
Suppresses RNF4-mediated ubiquitination, accumulates at sites of DNA damage, defective homologous recombination.
In cell line LoVo; does not undergo autocatalytic activation and is not transported to the Golgi apparatus.
Loss of catalytic activity and propeptide first cleavage. Abnormal accumulation in the early secretory pathway.
Loss of catalytic activity and propeptide second cleavage and removal. Abnormal accumulation in the early secretory pathway.
Loss of catalytic activity and, propeptide second cleavage and removal. Normal trafficking to the Golgi.
Phosphomimetic mutant. Localization in early endosome is increased.
Slight reduction in phosphorylation. Loss of phosphorylation and abnormal accumulation in the early secretory pathway; when associated with A-773.
Slight reduction in phosphorylation. Loss of phosphorylation and abnormal accumulation in the early secretory pathway; when associated with A-775.
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.
Required for CTNNB1 accumulation and TCF transcription factor activity
Required for Wnt-activated receptor activity
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.
Does not significantly change the substrate specificity.
Ornithine homo-exchange is enhanced 18-fold. Vmax value 33-fold higher than wild-type.
28 X 19 AA approximate tandem repeats of E-E-S-X-X-X-H-X-X-P-X-X-T-X-T-X-X-X-P
Impaired nuclear focus formation, reduced interaction with PIAS and increased sensitivity to cisplatin.
Impairs the formation of the NEDD8-UBA3 thioester.
In NEDFIH; unknown pathological significance.
In NEDFIH; unknown pathological significance; decreased protein abundance in homozygous patient cells; patient cells show a decreased amount of neddylated proteins.
NEDD8-activating enzyme E1 regulatory subunit
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.
Interaction with argonaute family proteins
Sufficient for interaction with AGO1 and AGO4
Sufficient for interaction with AGO1, AGO3 and AGO4
Trinucleotide repeat-containing gene 6A protein
Does not affect cleavage by CASP8 in response to alpha-ketoglutarate.
Impaired cleavage by CASP8 in response to alpha-ketoglutarate.
Low spontaneous pyroptosis-inducing activity.
Spontaneous pyroptosis-inducing activity.
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.
Enhances the interaction with RP2. Does not induce a mitotic arrest resulting from the loss of the microtubule-based mitotic spindle. Induces release of myristoylated proteins from UNC119. Interacts with ARL2BP, GOLGA4, PDE6D and UNC119.
In JBTS35; decreased release of NPHP3 and INPP5E cargos to the cilium.
In RP83; unknown pathological significance.
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.
Found in a patient with congenital insensitivity to pain; uncertain pathological significance.
In HSAN5; impaired processing of the precursor to mature NGF; nearly abolishes secretion; loss of function in stimulating cell differentiation; loss of the ability to activate the NTRK1 receptor.
In HSAN5; uncertain pathological significance.
Decreased bis(monoacylglycero)phosphate (BMP) hydrolase activity.
Loss of 2-arachidonoyglycerol hydrolase activity.
Loss of bis(monoacylglycero)phosphate (BMP) hydrolase activity.
Markedly reduced affinity for histone H3 and reduced histone H3 phosphorylation.
Markedly reduced histone H3 phosphorylation.
Strongly reduced enzyme activity, markedly reduced affinity for histone H3.
In NI-CINA; Neutropenic and elevated monocytosis but no history of infectious complications. No effect on DNA binding but diminished GFI1 repression activity.
In SCN2; zero neutrophil count. marked monocytosis and reduced T- and B-lymphocyte number leading to recurrent infectious complications. Abolishes recognition of DNA binding site of zinc finger. Diminished repression activity and elevated ELA2 expression. No effect on repression of CDKN1A/p21 transcription.
Influences on amino acid transport capacity
Sodium-coupled neutral amino acid transporter 4
KH domain-containing, RNA-binding, signal transduction-associated protein 2
(Microbial infection) Cleavage by protease 2A of enterovirus 71
(Microbial infection) Cleavage; by HAV protein 3ABC
(Microbial infection) Cleavage; by HCV and hepatitis GB virus B NS3/4A protease complex
(Microbial infection) Cleavage; by viral Seneca Valley virus protease 3C
(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in UFM1)
Abolished ability to bind and activate IRF3.
Abolished ubiquitination by TRIM31; when associated with R-10 and R-311.
Abolished ubiquitination by TRIM31; when associated with R-10 and R-461.
Abolished ubiquitination by TRIM31; when associated with R-311 and R-461.
Complete loss of cleavage by Seneca Valley virus protease 3C.
Complete loss of cleavage by enterovirus 71.
Complete loss of cleavage by protease 2A of enterovirus 71.
Decreased cleavage by CASP3. Abolished cleavage by CASP3; when associated with A-429.
Decreased cleavage by CASP3. Abolished cleavage by CASP3; when associated with A-490.
Impairs ability to induce IFN-beta. Loss of interaction with the ATG5-ATG12 conjugate.
Impairs filament formation and abolishes antiviral signaling activity.
Mitochondrial antiviral-signaling protein
No cleavage by HCV and hepatitis GB virus BNS3/4A protease complex.
No effect on cleavage by NS3/4A protease complex.
No effect on cleavage by Seneca Valley virus protease 3C.
No interaction with TRAF6; when associated with D-155.
No interaction with TRAF6; when associated with D-457.
Associated with coronary artery disease; no effect on ligand-specificity; may increase levels of rolling and adhesion of neutrophils and peripheral blood mononuclear cells to the endothelium; may induce constitutive stimulation of the MAPK signaling pathway, in the absence of leukocyte adhesion.
Decreased adhesion to cells expressing SELPLG.
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.
Decrease in target mRNA abundance and 10-fold decrease in RNA binding affinity; when associated with A-130.
Decrease in target mRNA abundance and 10-fold decrease in RNA binding affinity; when associated with A-97.
Decrease in target mRNA abundance and 124-fold decrease in RNA binding affinity; when associated with A-190.
Decrease in target mRNA abundance and 124-fold decrease in RNA binding affinity; when associated with A-193.
Decrease in target mRNA abundance and 20-fold decrease in RNA binding affinity; when associated with A-120.
Decrease in target mRNA abundance and 20-fold decrease in RNA binding affinity; when associated with A-124.
KH domain-containing RNA-binding protein QKI
Qua1 domain; involved in homodimerization
Altered Golgi structure with an engorged lumen. Interacts with ARFIP2, GOLGA4, RGPD8, SCOC and UNC119.
Loss of interaction with ARFIP1 and ARFIP2.
In isoform 2, isoform 4, isoform 6 and isoform 7.
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1
Nascent polypeptide-associated complex subunit alpha-2
Chloride intracellular channel protein 5
Helical; Note=After insertion into the membrane
Does not affect post-translational maturation; does not affect membrane sorting, does not affect pH homeostasis in recycling endosomes, does not affect cargo trafficking.
Does not affect post-translational maturation; does not affect membrane sorting; does not affect pH homeostasis in recycling endosomes; does not affect cargo trafficking.
In MRXSCH; decreases protein stability; increased ubiquitination; impairs acidification of endosomes; reduces localization to recycling endosomes; impairs trafficking to plasma membrane; reduces uptake of recycling endosomal cargo.
In MRXSCH; reduces oligosaccharide maturation; decreases protein stability; partially accumulated in the ER; impairs acidification of endosomes; reduces localization to recycling endosomes; impairs trafficking to plasma membrane; reduces uptake of recycling endosomal cargo.
In MRXSCH; reduces oligosaccharide maturation; largely retained in the ER; strongly reduces localization to recycling endosomes; strongly impairs trafficking to plasma membrane; strongly reduces uptake of recycling endosomal cargo.
Breakpoint for translocation to form AML1-EAP in T-MDS and CML, to form type II MACROD1-RUNX1 fusion protein and to form RUNX1-CBFA2T2 in acute myeloid leukemia
Breakpoint for translocation to form AML1-EMV-1 (or AML1-EAP) in CML and T-MDS, to form AML1-MTG8 (ETO) in AML-M2, to form AML1-CBFA2T3 in therapy-related myeloid malignancies, to form AML1-MECOM in CML and to form type I MACROD1-RUNX1 fusion protein
Disrupts AML1-MTG8/ETODNA-binding, decreases AML1-MTG8/ETO transforming activity.
Disrupts interaction of AML1-MTG8/ETO with CBFB, no effect on AML1-MTG8/ETO-mediated transformation activity.
Loss of heterodimerization and impaired phosphorylation.
Loss of heterodimerization and reduced EP300 phosphorylation induction.
Loss of heterodimerization. Disrupts interactionof AML1-MTG8/ETO with CBFB, no effect on AML1-MTG8/ETO-mediated transformation activity.
Reduced phosphorylation; when associated with A-273.
Reduced phosphorylation; when associated with A-276.
Strongly reduces DNA-binding, impaired phosphorylation and reduced EP300 phosphorylation induction.
10 X 10 AA tandem approximate repeats of P-A-K-P-Q-P-Q-Q-P-X
V-set and transmembrane domain-containing protein 2A
In short isoform 1, due to a stop-gain single nucleotide variant, has reduced half-life due to increased proteasomal degradation, has reduced solubility and increased tendency to form aggregates, increased localization to the nucleus.
WD repeat and FYVE domain-containing protein 2
PiggyBac transposable element-derived protein 2
In PDB6; enhances nuclear localization; increases expression levels; R-937 containing osteoclasts induced by treatment of peripheral blood mononuclear cells with CSF1 and TNFSF11 exhibit a greater number of nuclei, as well as a larger surface area than did those from the control individuals.
In PDB6; unknown pathological significance.
In COXPD31; unknown pathological significance.
In DYT6; mild phenotype; does not affect activity.
StAR-related lipid transfer protein 7, mitochondrial
Interchain (with C-208); in dimeric form
Interchain (with C-215); in dimeric form
Ankyrin repeat and LEM domain-containing protein 1
Probable loss of endonucleolytic activity. Fails to induce DNA damage response upon leptomycin-mediated nuclear localization. No nuclear translocation upon treatment with DNA damaging agents. Steady state cytoplasmic localization is not affected.
Slight increase in nuclear localization.
Coiled-coil domain-containing protein 103
In CILD17; unknown pathological significance; hypomorphic variant; reduced cilia beat amplitude in homozygous nasal respiratory cells; does not fully rescue abnormal phenotype in a zebrafish animal model.
Serine/arginine repetitive matrix protein 4
Serine/arginine repetitive matrix protein C-terminal
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.
Transforming growth factor beta activator LRRC32
Tyrosine-protein phosphatase non-receptor type 13
Found in a patient with autoimmune manifestations; unknown pathological significance.
Found in a patient with autoimmune manifestations; unknown pathological significance; decreased CDC42 activation in patient platelets.
Found in a patient with autoimmune manifestations; unknown pathological significance; decreased expression in patient platelets and activated T-cells; decreased CDC42 activation in patient platelets.
Found in a patient with autoimmune manifestations; unknown pathological significance; decreased expression in patient platelets and activated T-cells; impaired CDC42 activation in patient platelets.
Transmembrane and coiled-coil domain protein 3
Zinc finger and SCAN domain-containing protein 29
General transcription factor II-I repeat domain-containing protein 2A
AF1; mediates transcriptional activation
AF2; mediates transcriptional activation
AF3; mediates transcriptional activation (in isoform B)
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.
Mediates transcriptional transrepression (in isoform A)
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.
Increases affinity for ATP and decreases affinity for acetyl-CoA. Increases acetyl-CoA production.
Loss of catalytic activity but can bind ATP normally.
Retains 30% of wild-type activity. Refractory to inhibition by acetyl-CoA. Exhibits a 10-fold increase in the Km for pantothenate.
Induces constitutive protein kinase activity.
Kinase defective mutant, abolishes activity.
Mimicks phosphorylation state and displays a slightly higher protein kinase activity.
Mimicks phosphorylation state and induces constitutive protein kinase activity.
Phosphothreonine; by MAPK11, MAPK14, MAPK4, MAPK6 and PKA
In a colorectal adenocarcinoma sample; somatic mutation; greatly reduces kinase activity, increases cell proliferation and cell survival.
In a lung neuroendocrine carcinoma sample; somatic mutation; greatly reduces kinase activity, increases cell proliferation, cell adhesion and cell survival.
In an ovarian mucinous carcinoma sample; somatic mutation; greatly reduces kinase activity, increases cell proliferation and cell survival.
Loss of kinase activity at low concentrations of ATP.
Loss of phosphorylation by ROCK1, catalytically inactive.
Phosphoserine; by autocatalysis and DAPK1
Phosphothreonine; by autocatalysis and ROCK1
Phosphothreonine; by autocatalysis, DAPK1 and ROCK1
Predominantly cytoplasmic localization; phosphomimetic.
Predominantly nuclear localization; when associated with A-427 and A-434.
Predominantly nuclear localization; when associated with A-427 and A-441.
Predominantly nuclear localization; when associated with A-434 and A-441.
Does not affect interaction with the conventional FFAT motif of OSBPL1A. Impairs the interactions of the MSP domain with the phosphorylated FFAT motif of STARD3.
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.
Involved in binding the phosphorylated serine of the phospho-FFAT motif
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
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.
cAMP-dependent protein kinase inhibitor beta
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.
HA-stretch; determines single-channel conductance in 5-HT3 receptors
Amiloride-sensitive sodium channel subunit gamma
In LIDLS2; increased sodium channel activity.
Transforming acidic coiled-coil-containing protein 1
Transforming acidic coiled-coil-containing protein C-terminal
Rap guanine nucleotide exchange factor-like 1
Abolishes interaction with DLG4. No effect on synaptic localization.
Active breakpoint cluster region-related protein
Loss of GAP activity; when associated with A-683.
Reduces GAP activity. Loss of GAP activity; when associated with A-795.
In RP80; also found in a patient with Leber congenital amaurosis and renal failure; unknown pathological significance; decreased localization to the basal body.
In RP80; unknown pathological significance.
In RP80; unknown pathological significance; decreased localization to the basal body.
In SRTD9 and RP80; unknown pathological significance; partial to complete loss of basal body localization and increase of cytoplasmic localization.
In SRTD9; disease phenotype consistent with Mainzer-Saldino syndrome.
In SRTD9; impairs centrosomal localization.
In SRTD9; partial to complete loss of basal body localization and increase of cytoplasmic localization.
In SRTD9; partial to complete loss of basal body localization and increase of cytoplasmic localization; partial loss of function.
In SRTD9; unknown pathological significance.
Intraflagellar transport protein 140 homolog
No effect on localization to the basal body.
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.
Conserved oligomeric Golgi complex subunit 5
Breakpoint for translocation to form IL2/TNFRSF17 oncogene
Tumor necrosis factor receptor superfamily member 17
Flagellum-associated coiled-coil domain-containing protein 1
In DFNX2; somatic mosaicism in 50% of the peripheral blood lymphocytes.
POU domain, class 3, transcription factor 4
Hepatocyte growth factor-regulated tyrosine kinase substrate
Strongly reduced ubiquitin-binding. Reduced degradation of ubiquitinated EGFR.
Abolished mitochondrial tRNA methylation. Does not affect mitochondrial tRNA 5'-end processing.
In COXPD30; decreased protein abundance; impaired mitochondrial tRNA processing; has no effect on steady-state mitochondrial-mRNA and mitochondrial-tRNA levels but indirectly impairs mitochondrial translation.
(Microbial infection) Interaction with HCV NS5A
Decreased protein interaction with HCVNS5A.
Increased protein interaction with HCVNS5A.
Protein kinase C and casein kinase substrate in neurons protein 2
In HSAN8; no effect on nuclear localization; not able to induce histone H3-K9 dimethylation.
In HSAN8; reduced protein amount; results in protein aggregation.
In SPGF60; unknown pathological significance.
Telomere repeats-binding bouquet formation protein 1
In CMAVM1; unknown pathological significance.
Does not inhibit G4-DNA-binding; when associated with A-65.
Does not inhibit G4-DNA-binding; when associated with A-66.
Greatly reduces G4-RNA-binding; when associated with P-59.
Greatly reduces G4-RNA-binding; when associated with P-63.
Inhibits G4-DNA-binding; when associated with L-55 and L-59.
Inhibits G4-DNA-binding; when associated with L-55 and L-63.
Inhibits G4-DNA-binding; when associated with L-59 and L-63.
Loss of ATPase activity; results in an increased in G4-DNA- and G4-RNA-binding stabilities, increases localization in cytoplasmic stress granules and loss of mRNA deadenylation and mRNA decay.
Necessary for interaction with single-stranded DNA at the 3'-end of the G4-DNA structure
Necessary for nuclear and nucleolar caps localizations
Reduces G4-RNA binding; when associated with A-57, A-59, A-62 and A-63.
Reduces G4-RNA-binding; when associated with G-54, A-57, A-59 and A-62.
Reduces G4-RNA-binding; when associated with G-54, A-57, A-59 and A-63.
Reduces G4-RNA-binding; when associated with G-54, A-57, A-62 and A-63.
Reduces G4-RNA-binding; when associated with G-54, A-59, A-62 and A-63.
Required for recruitment to cytoplasmic stress granules
In LEPD; no effect on secretion; does not bind or activate LEPR.
Lymphocyte antigen 6 complex locus protein G6d
Tissue-type plasminogen activator chain A
Tissue-type plasminogen activator chain B
Methyltransferase-like protein 17, mitochondrial
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.
Necessary and sufficient for localization to autophagosome
EEF1AKMT4-ECE2 readthrough transcript protein
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.
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.
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.
In XLP1; abolishes interaction with SLAMF1.
In XLP1; loss of interaction with CD84 and reduced affinity for SLAMF1.
In XLP1; loss of interaction with CD84; loss of interaction with non-phosphorylated SLAMF1.
In XLP1; loss of interaction with CD84; strongly reduced affinity for SLAMF1.
In XLP1; reduced affinity for SLAMF1 and FYN.
In XLP1; reduced protein stability and reduced affinity for SLAMF1 and FYN.
In XLP1; reduced protein stability and reduced affinity for SLAMF1, decreases interaction with FYN.
In XLP1; reduced protein stability and strongly reduced affinity for SLAMF1, decreases interaction with FYN.
In XLP1; reduced protein stability and strongly reduced affinity for SLAMF1, disrupts interaction with FYN.
In XLP1; unknown pathological significance.
In one XLP1 patient; unknown pathological significance.
Impaired homotrimer formation. No effect on LRP6 binding although LRP6 phosphorylation is significantly reduced.
Loss of calcium binding and increased homotrimer stability; when associated with Ala-1078.
Loss of calcium binding and increased homotrimer stability; when associated with Ala-1084.
Abolishes phosphorylation by CaMK2. No effect on kinetic parameters.
In DRDSPRD; loss of sepiapterin reductase activity.
COX assembly mitochondrial protein homolog
Decreases dimerization. No effect on degradation of ANP. Retains the ability to degrade an aberrant form of ANP, when in the presence of both ANP and the aberrant ANP.
Increases catalytic rate towards INS and amyloid; when associated with C-132.
Increases catalytic rate towards INS and amyloid; when associated with C-184.
Increases catalytic rate towards INS and amyloid; when associated with C-426.
Increases catalytic rate towards INS and amyloid; when associated with C-817.
Increases catalytic rate towards INS and amyloid; when associated with C-828.
Increases catalytic rate towards INS and amyloid; when associated with C-899.
Decreased affinity for tRNA. Strongly decreased affinity for tRNA; when associated with A-419.
Decreased affinity for tRNA. Strongly decreased affinity for tRNA; when associated with A-420.
Increased affinity for tRNA and increased dihydrouridine synthesis; when associated with K-294.
Increased affinity for tRNA and increased dihydrouridine synthesis; when associated with K-305.
tRNA-dihydrouridine(20) synthase [NAD(P)+]-like
In DFNA2B; unknown pathological significance.
In CVT; also in Charcot-Marie-Tooth disease-like foot deformities.
Kringle-containing protein marking the eye and the nose
In ALS; unknown pathological significance.
In ALS; unknown pathological significance; leads to filamentous aggregate formation.
In NEDIES; in the neuroblastoma cell line SH-SY5Y, in which NCDN has been knocked out, does not rescue impaired neurite formation following retinoic acid treatment, contrary to wild-type; in these cells, associated with markedly decreased phosphorylation of ERK1/ERK2, compared to wild-type, suggesting impaired GRM5 activation.
In NEDIES; in the neuroblastoma cell line SH-SY5Y, in which NCDN has been knocked out, does not rescue impaired neurite formation following retinoic acid treatment, contrary to wild-type; no effect on phosphorylation of ERK1/ERK2.
In NEDIES; unknown pathological significance; in the neuroblastoma cell line SH-SY5Y, in which NCDN has been knocked out, does not rescue impaired neurite formation following retinoic acid treatment, contrary to wild-type; no effect on phosphorylation of ERK1/ERK2.
All-trans-retinol dehydrogenase [NAD(+)] ADH4
In ATFB13; the mutant results in highly reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system.
In ATFB13; the mutant results in reduced sodium currents when coexpressed with SCN5A in a heterologous expression system.
In DEE52; severely decreased channel localization at the cell membrane.
In DEE52; unknown pathological significance.
In GEFSP1; can rescue the loss of function and defective trafficking to cell membrane phenotype of the SCN1A variant Thr-1852.
Probable disease-associated variant found in a patient with idiopathic childhood epilepsy; de novo mutation; loss of function in increasing sodium channel activity.
Probable disease-associated variant found in a patient with non-specific cardiac conduction defects.
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.
Sufficient for transactivation activity; sufficient for interaction with NOTCH1
Zinc finger MIZ domain-containing protein 1
Zmiz1 N-terminal tetratricopeptide repeat
In COD5; results in protein misfolding and retention in the endoplasmic reticulum.
Required for 11-cis-retinal regeneration
Guanine nucleotide exchange factor subunit RIC1
In CATIFA; patient cells contain normally spliced transcripts corresponding to protein variant P-1265 but also transcripts that fail to splice due to intron 24 retention leading to a stop codon at position 1266; loss-of-function variant affecting procollagen secretion.
In CATIFA; patient cells contain transcripts that fail to splice due to intron 24 retention leading to a stop codon at position 1266, but also normally spliced transcripts corresponding to protein variant P-1265; loss-of-function variant affecting procollagen secretion.
Suppresses homodimerization, TNFR1 interaction, and apoptosis induction.
Suppresses homodimerization, and TNFR1 interaction.
Tumor necrosis factor receptor superfamily member 25
Pancreatic secretory granule membrane major glycoprotein GP2
Chondroitin sulfate N-acetylgalactosaminyltransferase 1
Found in a patient with neuropathy; unknown pathological significance; loss of GalNAc-transferase activity; no effect on protein expression.
In SDJLABA; loss of GalNAc-transferase activity.
In SDJLABA; reduced GalNAc-transferase activity.
In SDJLABA; severely reduced GalNAc transferase activity.
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
Coiled-coil domain-containing protein 148
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.
Trafficking protein particle complex subunit 6B
Acyl-CoA:lysophosphatidylglycerol acyltransferase 1
Retinoid-inducible serine carboxypeptidase
In CMH8; with mid-left ventricular chamber thickening.
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.
Leucine-rich repeat-containing protein 10B
Found in a patient with myoclonic epilepsy; unknown pathological significance; results in decreased protein activity; less active in stimulating calcium release compared to wild-type.
Found in patients with severe progressive myoclonic epilepsy; unknown pathological significance; results in increased protein activity when associated with H-148; less active in stimulating calcium release when associated with H-148.
Found in patients with severe progressive myoclonic epilepsy; unknown pathological significance; results in increased protein activity when associated with I-153; less active in stimulating calcium release when associated with I-153.
U7 snRNA-associated Sm-like protein LSm10
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.
Cytoplasmic dynein 2 light intermediate chain 1
Follicular dendritic cell secreted peptide
Impairs the interaction with OLGA2/GM130 and cis-Golgi assembly.
Spindlin interactor and repressor of chromatin-binding protein
Loss of glycosylase and AP lyase activity.
No effect on glycosylase and AP lyase activity.
Proton donor; for beta-elimination activity
Proton donor; for delta-elimination activity
Strongly reduces strand AP lyase activity.
In CILD16; reduced tethering interaction between DNAH5 and tubulin.
Oxidative stress-induced growth inhibitor 2
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.
Found in a patient with Bardet-Biedl syndrome also carrying a frameshift mutation in BBS10 and variant R-834 in KIF7.
In a patient with Meckel-Gruber like syndrome also carrying Y-60 in TTC21B.
Abolishes enhancement of NFKBIA and NR3C1 sumoylation. No effect on NR3C1 transcriptional activity.
Alters specificity towards synthetic inhibitors.
B-cell scaffold protein with ankyrin repeats
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
Complete loss of EPO-induced STAT5 signaling suppression. Abolishes binding to JH1.
Complete loss of EPO-induced STAT5 signaling suppression. No effect on LIF-induced STAT3 signaling. Abolishes binding to JH1.
Complete loss of EPO-induced STAT5 signaling suppression. No suppression of JAK2 phosphorylation.
Complete loss of EPO/LIF-induced signaling inhibition. Abolishes binding to JH1.
Complete loss of EPO/LIF-induced signaling suppression.
Complete loss of EPO/LIF-induced signaling suppression. No inhibition of JAK2 phosphorylation.
Greatly impaired binding to Y429/Y431 phosphorylated EPOR.
Impaired binding to Y429/Y431 phosphorylated EPOR.
Little effect on EPO-induced STAT5 signaling suppression.
Little effect on EPO-induced signaling suppression.
No effect on EPO/LIF-induced signaling suppression. Partial suppression of JAK2 phosphorylation. No effect on binding to JH1. Loss of binding to IL12RB2.
No effect on binding to Y429/Y431 phosphorylated EPOR.
Partial loss of EPO-induced STAT5 signaling suppression. No effect on LIF-induced signaling suppression. Abolishes binding to JH1. Inhibits JAK2 phosphorylation.
Loss of antioxidant activity. Loss of S-palmitoylation.
Loss of antioxidant activity. No change in S-palmitoylation levels.
No change in antioxidant activity. No change in S-palmitoylation levels.
Transcription elongation factor A protein 2
RalBP1-associated Eps domain-containing protein 2
Abolishes binding to histone H3K9me without affecting the histone methyltransferase activity.
Histone-lysine N-methyltransferase EHMT2
Guanine nucleotide-binding protein G(i) subunit alpha-2
PxLPxI/L motif; mediates interaction with ANKRA2 and RFXANK
In ARWH1 and HYPT8; loss of G protein-coupled receptor signaling; no effect on localization to cell membrane; does not affect protein abundance.
In ARWH1 and HYPT8; loss of G protein-coupled receptor signaling; reduced localization to cell membrane; decreased protein abundance; increased protein degradation.
In ARWH1; loss of G protein-coupled receptor signaling; reduced localization to cell membrane; decreased protein abundance; increased protein degradation.
In HYPT8; loss of G protein-coupled receptor signaling; no effect on localization to cell membrane; does not affect protein abundance.
In HYPT8; loss of G protein-coupled receptor signaling; reduced localization to cell membrane; decreased protein abundance; increased protein degradation.
In HYPT8; unknown pathological significance.
In HYPT8; unknown pathological significance; no effect on G protein-coupled receptor signaling; no effect on localization to cell membrane; does not affect protein abundance.
Loss of G protein-coupled receptor signaling. Reduced localization to cell membrane. Decreased protein abundance. Increased protein degradation.
Golgi apparatus membrane protein TVP23 homolog
Golgi apparatus membrane protein TVP23 homolog B
DNA-directed RNA polymerase III subunit RPC6
In IMD101; unknown pathological significance.
Strongly impaired dsDNA-binding. No effect on interaction with POLR3C.
In BTD deficiency; not detectable protein levels; loss of biotinyl-transferase activity.
In BTD deficiency; profound and partial; 52% decrease in biotinyl-transferase activity.
Abolishes interaction with protein phosphatase PP1 subunits PPP1CB and PPP1CC; when associated with A-684.
Abolishes interaction with protein phosphatase PP1 subunits PPP1CB and PPP1CC; when associated with A-686.
Ribosomal RNA processing protein 1 homolog B
RANBP2-like and GRIP domain-containing protein 2
In MODY14; no effect on protein abundance; loss of function in insulin receptor signaling pathway.
6000 fold increase in deacetylase activity.
Abolishes nuclear export; when associated with A-155; A-358 and A-486.
Abolishes nuclear export; when associated with A-181; A-358 and A-486. Abolishes phosphorylation by MARK2 and MARK3, interaction with 14-3-3 and localization to the cytoplasm.
Abolishes nuclear export; when associated with A-192; A-1118 and A-358.
Abolishes nuclear export; when associated with A-192; A-1118 and A-486.
Phosphoserine; by MARK2, MARK3 and PKD/PRKD1
Uncharacterized protein C10orf67, mitochondrial
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
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.
Fibronectin type III domain-containing protein 4
Found in a patient with Joubert syndrome; unknown pathological significance.
Abolishes interaction with CDC42BPB and MYZAP.
In HLD18; decreased function in sphingolipid biosynthetic process.
In HLD18; decreased function in sphingolipid biosynthetic process; reduced protein levels; increased protein degradation.
In HLD18; unknown pathological significance.
Abolishes IRS1 tyrosine phosphorylation. No cell proliferation.
Associated with atopic asthma and cedar pollen sensitization.
Associated with atopic dermatitis; lowered total IgE concentration; no effect on IL4-induced signal transduction.
Associated with cedar pollen sensitization.
Increased IL4-induced cell proliferation and STAT6 activation.
Loss of CD23 gene induction; when associated with F-575 and F-603.
Loss of CD23 gene induction; when associated with F-575 and F-631.
Loss of CD23 gene induction; when associated with F-603 and F-631.
Required for IL4-induced gene expression
Required for IRS1 activation and IL4-induced cell growth
Soluble interleukin-4 receptor subunit alpha
Interacts with hydroxy-aryl-aldehyde inhibitors
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
Membrane-associated phosphatidylinositol transfer protein 3
Greatly reduced PTPN11 binding; no PTPN11 phosphorylation; no effect on STAT3 phosphorylation.
In LEPRD; unknown pathological significance.
No effect on PTPN11 nor STAT3 phosphorylation.
No effect on PTPN11 phosphorylation; no STAT3 phosphorylation.
Sperm protein associated with the nucleus on the X chromosome D
Abolishes regulatory effect of DYRK1A on alternative splicing of MAPT/Tau exon 10.
No effect on regulation of alternative splicing of MAPT/Tau exon 10 by DYRK1A.
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.
Important for selectivity against geranylgeranyl diphosphate
Protein farnesyltransferase subunit beta
Removes the steric hindrance that normally precludes geranylgeranyl diphosphate binding. Reduces farnesyltransferase activity and confers geranylgeranyltransferase activity.
Chromodomain-helicase-DNA-binding protein 9
Abolishes interaction with ADRB2 and no increase in cellular abundance of ADRB2.
Platelet-derived growth factor receptor-like protein
A disintegrin and metalloproteinase with thrombospondin motifs 5
Probable E3 ubiquitin-protein ligase HERC6
Ubiquitin carboxyl-terminal hydrolase 17-like protein 5
Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization.
Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Loss of iodide transport activity; when associated with A-242.
Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471.
Loss of localization to the cell membrane, significant loss of iodide transport activity but no effect on homodimerization. Reduced homodimerization; when associated with A-471. Loss of iodide transport activity; when associated with F-535.
No effect on localization to the cell membrane, iodide transport activity and homodimerization. Significant loss of homodimerization; when associated with A-242 or A243.
Significant loss of iodide transport activity but no effect on its localization to the cell membrane.
(Microbial infection) Cleavage; by C.botulinum neurotoxin type X (BoNT/X)
Growth arrest and DNA damage-inducible protein GADD45 beta
In isoform 2, isoform 6, isoform 7, isoform 8 and isoform 9.
Interleukin-1 receptor-associated kinase 1-binding protein 1
Loss of deubiquitination activity, no change in subcellular location.
In a pancreatic ductal adenocarcinoma sample; somatic mutation.
Confers hypersensitivity to hydroxyurea.
Disrupts interaction with BRCA2, no effect on homooligomerization, promotes interaction with XPO1 and cytoplasmic localization.
Impaired ubiquitination; when associated with R-58.
Impaired ubiquitination; when associated with R-64.
In BC; decreased ATPase activity in the presence of stoichiometric ss-DNA concentrations with respect to RAD51; 3 to 4-fold decrease of affinity for ATP.
In FANCR; causes dominant negative loss of function in interstrand cross-link repair; shows high basal DNA-independent ATPase activity; results in decreased DNA binding.
In FANCR; dominant negative; impaired function in DNA repair via homologous recombination; impaired DNA-binding and formation of nucleoprotein filaments; impaired DNA-dependent ATPase activity; no effect on subcellular location.
Nuclear export signal; masked by the interaction with BRCA2
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.
Leucine-rich repeat transmembrane neuronal protein 1
Higher frequency of homozygotes in a cohort of non-familial cardiomyopathy Japanese patients as compared to healthy controls.
Interaction with trimethylated histone H3 (H3K4)
7-methylguanosine phosphate-specific 5'-nucleotidase
CDK-activating kinase assembly factor MAT1
In MFM11; mislocated away from the A-band to the Z-disk.
In MFM11; unknown pathological significance; mislocated away from the A-band to the Z-disk.
ADP-ribosylation factor-like protein 6-interacting protein 1
In SPG61; unknown pathological significance.
Doublesex- and mab-3-related transcription factor C1
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.
Ectonucleoside triphosphate diphosphohydrolase 8
Reduces nuclear localization. Inhibits nuclear localization; when associated with A-93 and A-94.
Reduces nuclear localization. Inhibits nuclear localization; when associated with A-93 and A-95.
Reduces nuclear localization. Strongly reduces nuclear localization and interaction with TRIM28; when associated with A-85.
Reduces nuclear localization. Strongly reduces nuclear localization; when associated with A-94 and A-95.
Strongly reduces nuclear localization and interaction with TRIM28; when associated with A-86.
In PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082.
In PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082.
In NEDMABA; unknown pathological significance.
In isoform 2, isoform 6, isoform 8 and isoform 10.
No effect on endoplasmic reticulum location.
Glutathione-specific gamma-glutamylcyclotransferase 2
3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3
In Le(-); Loss of alpha (1,3/1,4)fucosyltransferase activity..
In Le(-); about 20% of alpha (1,3/1,4)fucosyltransferase activity.
In Le(-); less than 10% reduction in activity.
Breakpoint for translocation to form GOPC-ROS1 fusion protein
Breakpoint for translocation to form SLC34A2-ROS1 and CD74-ROS1 fusion proteins
Loss of phosphorylation at Y-2274 and loss of interaction with PTPN11.
Loss of phosphorylation at Y-2334 and loss of interaction with PTPN11.
Proto-oncogene tyrosine-protein kinase ROS
Exhibits increased in susceptibility to proteolysis by ADAMTS13.
In VWD1 and VWD3; defect in secretion and formation of multimers.
In VWD1; reduced secretion of homodimers and heterodimers with wild type VWD and increased degradation by the proteasome.
Reduced secretion and increased intracellular retention. Similar phenotype; when associated with R-1149.
Reduced secretion and increased intracellular retention. Similar phenotype; when associated with S-1169.
VWFA 1; binding site for platelet glycoprotein Ib
VWFA 3; main binding site for collagens type I and III
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.
Acyl-CoA dehydrogenase/oxidase C-terminal
Acyl-CoA dehydrogenase/oxidase N-terminal
Changed substrate specificity towards longer acyl chains; when associated with E-280.
In ACADMD; may alter splicing; decreased fatty acid beta-oxidation.
In ACADMD; mild or benign clinical phenotype.
In ACADMD; the thermostability is markedly decreased.
Loss of acyl-CoA dehydrogenase activity.
Loss of acyl-CoA dehydrogenase activity; when associated with E-280.
Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Narrower substrate specificity. Changed substrate specificity towards longer acyl chains; when associated with G-401. Loss of acyl-CoA dehydrogenase activity; when associated with T-410.
Reduces rate of electron transfer to ETF about six-fold.
Reduces rate of electron transfer to ETF three-fold.
Reduces rate of electron transfer to ETF two-fold.
Strongly reduced rate of electron transfer to ETF.
12 X 20 AA approximate tandem repeats of S-S-E-S-S-A-S-S-D-S-P-H-P-V-I-T-P-S-R-A
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.
28 kDa heat- and acid-stable phosphoprotein
Vacuolar protein sorting-associated protein VTA1 homolog
Abolishes RNA-binding; when associated with E-109 and Q-113.
Abolishes RNA-binding; when associated with N-105 and E-109.
Abolishes RNA-binding; when associated with N-105 and Q-113.
In MGCA1; decreased methylglutaconyl-CoA hydratase activity.
Methylglutaconyl-CoA hydratase, mitochondrial
Ciliary-associated calcium-binding coiled-coil protein 1
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.
Loss of interaction with AP2M1 and impaired endocytosis.
May be associated with susceptibility to dyslexia.
Breakpoint for translocation to form CBF-beta-MYH11 oncogene in AML, subtype M4EO
Required for interaction with DHX9 and PRMT5
In RP35 and CORD10; heterozygous compound with C-350; loss of localization to cell membrane.
In RP35 and CORD10; heterozygous compound with H-345; loss of localization to cell membrane.
No effect on localization to cell membrane.
Heterogeneous nuclear ribonucleoprotein H
Heterogeneous nuclear ribonucleoprotein H, N-terminally processed
In NEDCDS; unknown pathological significance.
N-acetylmethionine; in Heterogeneous nuclear ribonucleoprotein H, N-terminally processed
N-acetylmethionine; in Heterogeneous nuclear ribonucleoprotein H; alternate
In ECTD9; unknown pathological significance.
In SPGF35; the protein is not detected in patient spermatozoa.
In SPGF35; unknown pathological significance.
In SPGF35; weak amount of protein detected in patient spermatozoa.
Zinc finger CCHC domain-containing protein 10
FERM, ARHGEF and pleckstrin domain-containing protein 2
Breakpoint for translocation to form KIAA1549-BRAF fusion protein
In RP86; unknown pathological significance.
In UPB1D; complete loss of activity; abolishes formation of higher oligomers.
In UPB1D; strongly reduced activity; reduced formation of higher oligomers.
In UPB1D; unknown pathological significance; mildly reduced enzyme activity; no effect on formation of higher oligomers.
Loss of catalytic activity. Forms dimers, but no higher oligomers.
Phosphatidylinositol 3-kinase catalytic subunit type 3
Abolishes interaction with methylated p53.
Mediator of RNA polymerase II transcription subunit 19
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.
Cytochrome c oxidase subunit 7A2, mitochondrial
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.
In LMPHM13; unknown pathological significance.
Thrombospondin type-1 domain-containing protein 1
Translocating chain-associated membrane protein 1
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3
Coiled-coil domain-containing protein 113
Induces relocalization to cell membrane.
Store-operated calcium entry regulator STIMATE
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 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.
Required for P-body targeting and interaction with DCP1A
In AGS2; heterozygous compound with T-177.
In AGS2; heterozygous compound with T-177; reduces stability of the RNase complex.
In AGS2; heterozygous compound with a nonsense mutation; reduces stability of the RNase complex.
In AGS2; reduces stability of the RNase complex.
In CPPB1; reduced rate of decline in inositol phosphate accumulation after kisspeptin stimulation; prolonged phosphorylation of ERK.
In HH8; 65% reduction of inositol phosphate production.
In HH8; absence of inositol phosphate accumulation under kisspeptin challenge; normal affinity for kisspeptin.
In HH8; exhibit profoundly impaired signaling.
In HH8; mild reduction in ligand-stimulated activity across the ligand dose range.
In HH8; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in IL17RD.
In HH8; phenotype consistent with normosmic idiopathic hypogonadotropic hypogonadism; benign variant; the patient also carries a mutation in FGFR1.
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.
4 X 11 AA tandem repeats of [EGSA]-K-T-K-[EQ]-[GQ]-V-X(4)
Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform
Zinc finger and SCAN domain-containing protein 5A
Fibroblast growth factor-binding protein 2
Probable E3 ubiquitin-protein ligase MARCHF10
Important for enzyme activity, localization to cytoplasmic vesicles, and protein stability
Interchain (between small and large subunit)
Loss of enzyme activity with lipopolysaccharide, due to steric hindrance. No effect on activity with small, synthetic substrate.
Loss of glycosylation. No effect on enzyme activity or localization to cytoplasmic vesicles.
No effect on enzyme activity; when associated with E-345.
No effect on enzyme activity; when associated with E-379.
Abolishes protease activity. Stabilizes the protein.
Abolishes catalytic activity with N(6)-methyladenosine in single-stranded DNA.
Abolishes catalytic activity; when associated with A-277.
Abolishes catalytic activity; when associated with A-283.
No effect on catalytic activity with N(6)-methyladenosine in single-stranded DNA.
Altered regulation of oligomerization by phosphorylation at S-222.
Loss of regulation of oligomerization by phosphorylation at S-222.
10 X 10 AA tandem repeats of L-S-Q-E-S-[EQ]-V-E-E-P
Secreted Ly-6/uPAR domain-containing protein 2
G protein-activated inward rectifier potassium channel 2
EP300-interacting inhibitor of differentiation 2B
Putative POU domain, class 5, transcription factor 1B
Essential for binding to NHERF1 PDZ domain
Found in a patient with severe delayed speech, autism spectrum and Gilles de la Tourette disorders.
Short transient receptor potential channel 5
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.
Necessary for interaction with AP2A1, RAB11A, subcellular location, endocytosis activity and homooligomerization
Necessary for its cellular translocation to the plasma membrane
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.
Sodium/potassium-transporting ATPase subunit beta-1-interacting protein
Centriolar coiled-coil protein of 110 kDa
Loss of centrosome clustering and protection from anaphase catastrophe upon CDK2 inhibition in lung cancer cells.
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
Required for interaction with SPRED1 and SPRY2. Required for TESK1-mediated dephosphorylation of SPRY2 and SPRY2 inhibition of ERK phosphorylation
Guided entry of tail-anchored proteins factor 1
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 MSSGM1; results in loss of activity; does not affect affinity for Gly-tRNA.
Pseudouridylate synthase TRUB2, mitochondrial
Loss of interaction with SIAH1. Decreased SIAH1-induced proteasome-mediated ubiquitin-dependent degradation of AXIN1. No effect on interaction with GSK3B.
Isopentenyl-diphosphate Delta-isomerase 1
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.
Class E basic helix-loop-helix protein 40
Essential for interaction with BMAL1, E-box binding and repressor activity against the CLOCK-BMAL1 heterodimer
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.
Necessary for interaction with RXRA and repressor activity against RXRA
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.
Membrane-spanning 4-domains subfamily A member 10
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
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.
Abolishes sumoylation; when associated with R-732.
Abolishes sumoylation; when associated with R-774.
Breakpoint for translocation to form PAX3-NCOA1 oncogene
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.
Abolishes RNA binding; when associated with A-100.
Abolishes RNA binding; when associated with A-97.
RNA-binding protein with multiple splicing
Abolishes binding to 'Lys-6'-linked polyubiquitin chains and ability to inhibit E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer.
Does not affect binding to 'Lys-6'-linked polyubiquitin chains and ability to inhibit E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer.
Early placenta insulin-like peptide A chain
Early placenta insulin-like peptide B chain
Required for dimerization upon membrane association
Sufficient for RNA-binding and MSE-dependent splicing activity
2-iminobutanoate/2-iminopropanoate deaminase
Tumor necrosis factor ligand superfamily member 4
Advanced glycosylation end product-specific receptor
Complete loss of phosphorylation by PKC/PRKCZ.
Less monoubiquitinated product and resistant to degradation.
Citrate synthase-lysine N-methyltransferase CSKMT, mitochondrial
Inhibits citrate synthase-lysine methyltransferase activity.
In BBSOAS; decreases transcriptional activity.
Probable disease-associated variant found in a patient with early infantile epileptic encephalopathy.
Coiled-coil domain-containing protein 18
Found in a patient with intellectual disability; unknown pathological significance.
Necessary and sufficient for nuclear localization
In DEE9; disease features overlapping with Dravet syndrome.
In DEE9; disease features overlapping with Dravet syndrome; associated with Cys-206.
In DEE9; disease features overlapping with Dravet syndrome; associated with Pro-203.
In DEE9; unknown pathological significance.
No effect on inhibitory activity; when associated with A-80.
No effect on inhibitory activity; when associated with A-91.
Bactericidal permeability-increasing protein
No impairment of secretion and increased propensity for dimer formation.
No impairment of secretion and/or biological activity. Loss of dimer formation.
Poorly secreted. Loss of LPS-binding and biological activity.
Affects glycosylation status. Affects glycosylation status; when associated with Q-448.
Affects glycosylation status; when associated with Q-457.
Does not affect glycosylation status; when associated with Q-78.
Does not affect glycosylation status; when associated with Q-88.
Lysosomal cobalamin transport escort protein LMBD1
WTKF motif; mediates interaction with adapter protein complex 2 and is essential for its function in clathrin-mediated endocytosis of INSR
YERL motif; mediates interaction with adapter protein complex 2 and is essential for its function in clathrin-mediated endocytosis of INSR
Leucine-rich repeats and immunoglobulin-like domains protein 2
No Golgi targeting, accumulates in the cytoplasm.
Protein-associating with the carboxyl-terminal domain of ezrin
In OORS; defective GPI anchor biosynthesis in homozygous patient cells.
Phosphatidylinositol-glycan biosynthesis class F protein
Dual specificity protein phosphatase 13A
Loss of enzyme activity. No effect on interaction with MAP3K5.
Leucine-rich repeat-containing protein 18
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.
Melanoma antigen recognized by T-cells 1
Loss of interaction with SQSTM1 and PARD6B.
No effect on interaction with SQSTM1 and PARD6B.
41 X 10 AA approximate tandem repeats of [TN]-Q-[GSA]-[KRQT]-K-[ATGSV]-[ED]-[GTAS]-[ATIS]-[PQTAS]
Interaction with the C-terminus of SPBC25
Interaction with the N-terminus of SPBC25
Interaction with the NDC80-CDCA1 subcomplex
Decreased EIF4A3-binding; when associated with A-331.
Decreased EIF4A3-binding; when associated with A-334.
No effect on EIF4A3 incorporation into EJCs.
In HMSN6B; slightly decreased protein abundance.
In HMSN6B; unknown pathological significance.
In HMSN6B; unknown pathological significance; no effect on protein abundance.
In HMSN6B; unknown pathological significance; slightly decreased protein abundance.
In PCH1E; decreased protein abundance; loss of function in mitochondrial fission; no effect on localization to the mitochondrial outer membrane.
Mitochondrial outer membrane protein SLC25A46
No effect on EMC assembly but decreased membrane insertion of hydrophobic transmembrane helices-containing proteins by the EMC.
Associated with susceptibility to alcoholism.
Ras-specific guanine nucleotide-releasing factor RalGPS2
Required for stimulation of nucleotide exchange by RALA
Histone-lysine N-methyltransferase SETD1A
In EPEDD; affects the development of synapses in a mouse model overexpressing the human protein harboring this variant.
In NEDSID; causes DNA damage repair defects associated with nucleolytic degradation of nascent DNA at stalled replication forks.
N-acetylalanine; in Protein S100-A11, N-terminally processed
Protein S100-A11, N-terminally processed
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3); alternate
Decreases binding to Link domain of TNFAIP6; when associated with A-41 and A-42.
Decreases binding to Link domain of TNFAIP6; when associated with A-41 and A-45.
Decreases binding to Link domain of TNFAIP6; when associated with A-42 and A-45.
In AAT9; expression of the mutant protein is significantly decreased.
Gamma-secretase-activating protein 16 kDa C-terminal form
Gamma tubulin complex component C-terminal
Gamma tubulin complex component protein N-terminal
In PAMDDFS; unknown pathological significance.
40% increase in potassium current amplitude. Ratio of 1:1.
Abolishes currents without reducing channel protein expression.
Decrease of PKA stimulation. Ratio of 1:1.
Found in a patient with continuous spikes and waves during sleep; unknown pathological significance.
Found in a patient with isolated myokymia; leads to a shift of voltage-dependent activation.
In BFNS1 and DEE7; 20%-40% reduction of wt current in heteromeric channels.
In BFNS1 and DEE7; decreases the voltage-dependence of the channel.
In BFNS1; 30%-60% reduction of wt current in heteromeric channels.
In BFNS1; also in patients with infantile seizures.
In BFNS1; minor effect on maximal current but clearly exhibits a faster rate of deactivation.
In BFNS1; moderate effect; less than 50% reduction in current compared with wt heteromeric channels.
In BFNS1; phenotype manifestations include myokymia in some patients; leads to a shift of voltage-dependent activation of the channel and a dramatic slowing of activation upon depolarization.
In BFNS1; unknown pathological significance.
In DEE7; gain-of-function mutation; results in loss of voltage-dependent channel gating and highly increased potassium currents.
In DEE7; patient also manifests dyskinesia.
In DEE7; reduces channel currents by more than 50% in homomeric channels.
More than 50% reduction of wt heteromeric current. Ratio of 1:1 and 1:1:2.
Potassium voltage-gated channel subfamily KQT member 2
Eukaryotic translation initiation factor 1b
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.
Abolishes autoinhibition, leading to constitutive kinase activity.
Abolishes autophosphorylation at Thr-423.
Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-83.
Abolishes interaction with CDC42, leading to strongly decreased activity; when associated with L-86.
Abolishes kinase activity; when associated with R-299.
Decreases CDC42-stimulated activity and autophosphorylation.
In IDDMSSD; gain of function; enhanced PAK1 kinase activity and significantly reduced homodimerization.
In IDDMSSD; gain-of-function; enhanced PAK1 kinase activity and significantly reduced homodimerization.
Phosphothreonine; by autocatalysis, BRSK2 and PDPK1
Strongly decreases activity. Abolishes kinase activity; when associated with N-389.
Interaction with the cytoplasmic tail of GP1BA
Abolishes CUL3-binding and ability to mediate monoubiquitination of NOLC1 and TCOF1.
Abolishes substrate-binding and ability to mediate monoubiquitination of NOLC1 and TCOF1.
Kelch repeat and BTB domain-containing protein 8
Abolished phosphorylation by PKB/AKT1 in response to EGF signaling.
Interacts with DUSP and ubiquitin-like 1 domains and is required for USP4 activation
Loss of thiol-dependent deubiquitinase activity. Its ubiquitination by TRIM21 is enhanced. Does affect interaction with HAS2. Does not deubiquitinate HAS2.
Lowers affinity for ubiquitin characterized by a 10-fold increase in ubiquitin release and a slight reduction in ubiquitin binding.
Mimics phosphorylation; promoting association with RHEB.
Moderate reduction in thiol-dependent deubiquitinase activity.
Necessary for interaction with RB1 and RBL2
Required for USP4 activation by providing conformational flexibility between the DUSP and catalytic domains
Severe reduction in thiol-dependent deubiquitinase activity.
Transmembrane and immunoglobulin domain-containing protein 1
Phospho-regulated basic and hydrophobic (PRBH) motif
Abolishes cAMP-induced nuclear localization.
Brefeldin A-inhibited guanine nucleotide-exchange protein 1
DCB; DCB:DCB domain and DCB:HUS domain interaction
No effect on cAMP-induced nuclear localization.
Abolishes KAT8 histone acetyltransferase activity.
Reduces KAT8 histone acetyltransferase activity.
Required for activation of KAT8 histone acetyltransferase activity
Strongly reduces KAT8 histone acetyltransferase activity.
Haloacid dehalogenase-like hydrolase domain-containing protein 2
EP300-interacting inhibitor of differentiation 1
Leucine-rich repeat and fibronectin type-III domain-containing protein 3
Complete loss of activity; when associated with K-233.
Complete loss of activity; when associated with S-407.
Decreases glycine amidinotransferase activity.
Glycine amidinotransferase, mitochondrial
In CCDS3; decreases glycine amidinotransferase activity.
In CCDS3; loss of glycine amidinotransferase activity.
In CCDS3; unknown pathological significance; reduces glycine amidinotransferase activity.
In FRTS1; results in GATM protein aggregation; GATM deposits affect mitochondrial morphology and are associated with increased ROS production, activation of the NLRP3 inflammasome and enhanced expression of the profibrotic cytokine IL-18.
In FRTS1; results in GATM protein aggregation; GATM deposits affect mitochondrial morphology leading to abnormal and elongated mitochondria.
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
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
Endogenous retrovirus group 3 member 1 Env polyprotein
Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with H-379.
Impairs binding to 2'-O-methylated 3'-end of piRNAs; when associated with Y-381.
Omega-N-methylarginine; by PRMT5; alternate
Probable disease-associated variant found in a patient with azoospermia.
Probable disease-associated variant found in a patient with azoospermia; requires 2 nucleotide substitutions.
Required for binding 2'-O-methylated 3'-end of piRNAs
(Microbial infection) Interaction with HCV NS2 and HCV E2
(Microbial infection) Interaction with JEV NS2B
Associated with change in bone mineral density.
Regulating synaptic membrane exocytosis protein 4
WD repeat and SOCS box-containing protein 1
FXYD domain-containing ion transport regulator 4
Abolishes autoubiquitination. Does not affect phosphorylation.
Abolishes phosphorylation but not autoubiquitination; when associated with A-205.
Abolishes phosphorylation but not autoubiquitination; when associated with A-39.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-635.
Abolishes poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1; when associated with A-641.
Impairs poly(ADP-ribose)-binding and poly-ADP-ribosylation by PARP1.
In a patient with non small cell lung carcinomas.
In a patient with non small cell lung carcinomas; homozygous.
Associated with susceptibility to T1D19.
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.
NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial
Abolishes binding to PEX19 without affecting targeting to peroxisomes; when associated with D-134.
Abolishes binding to PEX19 without affecting targeting to peroxisomes; when associated with P-125.
Dual specificity mitogen-activated protein kinase kinase 3
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.
Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with Q-643.
Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with S-154.
Ubiquitin carboxyl-terminal hydrolase 20
Acetylserotonin O-methyltransferase dimerisation
Important for substrate specificity; for pyrophosphatase activity
Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein
Proton acceptor; for pyrophosphatase activity
Strong decrease in pyrophosphatase activity.
Sodium- and chloride-dependent GABA transporter 2
Significantly accumulates in the nucleus. Increases apoptotic activity. Does not interact with XPO1.
Abolishes activation of STK11/LKB1; when associated with A-240.
Abolishes activation of STK11/LKB1; when associated with A-243.
Chymotrypsin-like elastase family member 3B
Hydroxysteroid dehydrogenase-like protein 2
Secretory carrier-associated membrane protein 5
Testis-specific chromodomain protein Y 2
ATP-binding cassette sub-family C member 2
Decreased expression; altered subcellular localization; altered transporter activity.
Decreased expression; altered subcellular localization; decreased transporter activity.
Fails to transport methotrexate and leukotriene C4. Does not affect estradiol glucuronide transport.
Fails to transport methotrexate, leukotriene C4 and estradiol glucuronide.
Fails to transport methotrexate; reduces leukotriene C4 transport. Does not affect estradiol glucuronide transport.
In DJS; decreased expression and mislocation to the endoplasmic reticulum.
In DJS; impaired transport from the endoplasmic reticulum to the apical plasma membrane associated with impaired maturation.
In DJS; protein is properly localized at the plasma membrane, but transporter activity is impaired.
ER degradation-enhancing alpha-mannosidase-like protein 3
In CDG2V; unknown pathological significance.
Pyrrolidone carboxylic acid; in form big gastrin
Pyrrolidone carboxylic acid; in form gastrin
Small decrease in ratio of gastrin-17 versus gastrin-34 production. No change in ratio of gastrin-17 versus gastrin-34 production; when associated with D-86.
Small increase in ratio of gastrin-17 versus gastrin-34 production. No change in ratio of gastrin-17 versus gastrin-34 production; when associated with F-87.
Connector enhancer of kinase suppressor of ras 3
DNA-directed RNA polymerase II subunit RPB9
In PCH7; reduced protein levels; decreased function in snRNA 3'-end processing.
1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
65% loss of 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity.
67% loss of 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity.
Associated with increased hepatic fat content and serum aspartate aminotransferase concentrations; probable gain-of-function variant; 2-fold increase in 1-acylglycerol-3-phosphate O-acyltransferase/lysophosphatidic acid acyltransferase activity; results on glycerolipid hydrolysis activity are controversial with reduction in triacylglycerol, diacylglycerol and monoacylglycerol hydrolase activity or no effect compared to wild-type in which this activity may be very low; does not affect subcellular location, nor association with lipid droplets.
Associated with lower hepatic fat content in African Americans.
In NAFLD1; unknown pathological significance.
No effect on 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity.
No effect on 1-acylglycerol-3-phosphate O-acyltransferase catalytic activity. Almost completely abolishes triacylglycerol, diacylglycerol and monoacylglycerol hydrolase activity.
Zinc finger and SCAN domain-containing protein 12
95% reduction in activity; strong reduction of receptor binding.
Abolishes binding to Link domain of TNFAIP6.
Involved in GAG binding and receptor binding
Involved in dimerization, receptor binding and signaling
Loss of dimerization; slight reduction of activity.
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
In DMAN; lower protein expression. Fails to rescue the lysosomal trafficking defect in LYSET-deficient cells. Severe reduction of interaction with GNPTAB.
In DMAN; no protein expression. Fails to rescue the lysosomal trafficking defect in LYSET-deficient cells.
Rescues the lysosomal trafficking defect in LYSET-deficient cells.
In NMTC2; does not affect the interaction with ROBO1; decreased GTPase activator activity; in SLIT2 and ROBO1-mediated inhibition of CDC42.
In NMTC2; does not affect the interaction with ROBO1; slightly increased GTPase activator activity; in SLIT2 and ROBO1-mediated inhibition of CDC42.
SLIT-ROBO Rho GTPase-activating protein 1
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 causative ARID2 mutation.
In FSGSNEDS; disrupts localization to nuclear bodies.
Cation channel sperm-associated auxiliary subunit epsilon
Alteredarachidonate 12(S)-lipoxygenase activity and protein expression.
Complete loss of arachidonate 12(S)-lipoxygenase activity.
No effect on arachidonate 12(S)-lipoxygenase activity.
No effect onarachidonate 12(S)-lipoxygenase activity. No effect on the stereoselectivity of the oxygenation reaction.
Polyunsaturated fatty acid lipoxygenase ALOX12
Reduced arachidonate 12(S)-lipoxygenase activity. Alters the stereoselectivity of the oxygenation reaction.
Reduced arachidonate 12(S)-lipoxygenase activity. No effect on the stereoselectivity of the oxygenation reaction.
10-fold reduction in candidacidal activity of His3-(20-43)-peptide; when associated with E-32.
3-fold reduction in candidacidal activity of His3-(20-43)-peptide.
In histatin-3-2; loss of the proteolytic cleavage site.
No effect on candidacidal activity of His3-(20-43)-peptide.
Abolishes ubiquitination by the TRIM27:MAGEL2 E3 ubiquitin ligase complex and impairs retrograde transport.
Impairs retrograde transport from endosome to Golgi apparatus.
Cytochrome c1, heme protein, mitochondrial
Endothelial zinc finger protein induced by tumor necrosis factor alpha
NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial
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
U11/U12 small nuclear ribonucleoprotein 35 kDa protein
Enteropeptidase non-catalytic heavy chain
Impaired NO-mediated modification. Loss of NO-mediated modification; when associated with A-19 or A-20.
No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-19. Loss of NO-mediated modification; when associated with A-139.
No effect on NO-mediated modification. Impaired NO-mediated modification; when associated with A-20. Loss of NO-mediated modification; when associated with A-139.
Variant Ala-111. The measured range is 2-184.
Variant Glu-111. The measured range is 2-184.
Regulator of G-protein signaling protein-like
Allele TPMT*2; TPMT*2 allele frequency is 0.5%; seems to be restricted to the Caucasian population; 100-fold reduction in activity; protein shows enhanced degradation.
Allele TPMT*3A and allele TPMT*3B; very low activity; protein shows enhanced degradation leading to strongly reduced protein levels.
Allele TPMT*3B and allele TPMT*3C; reduced activity; protein shows enhanced degradation.
Allele TPMT*5; has very low activity when expressed in a heterologous system.
Decreases affinity for 6-mercaptopurine. Slightly decreases catalytic activity.
Abolishes LPIAT activity. No effect on LPGAT activity.
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.
27 X 6 AA repeats of [GEVSTPAN]-[ILMV]-[DE]-[RH]-[MLVI]-[GAV]
Heterogeneous nuclear ribonucleoprotein M
In CTLN1; decreased affinity for aspartate; decreased affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; decreased thermal stability; decreased affinity for aspartate; decreased affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; decreased thermal stability; decreased affinity for aspartate; decreased affinity for citrulline; loss of argininosuccinate synthase activity.
In CTLN1; decreased thermal stability; loss of argininosuccinate synthase activity.
In CTLN1; increased thermal stability; decreased affinity for aspartate; decreased affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; increased thermal stability; loss of argininosuccinate synthase activity.
In CTLN1; loss of argininosuccinate synthase activity.
In CTLN1; mild clinical course; no effect on affinity for aspartate; no effect on affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; mild; decreased affinity for aspartate; decreased affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; mild; no effect on affinity for aspartate; no effect on affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; no effect on affinity for aspartate; no effect on affinity for citrulline; decreased argininosuccinate synthase activity.
In CTLN1; no effect on thermal stability; decreased argininosuccinate synthase activity.
In CTLN1; severe clinical course; loss of argininosuccinate synthase activity.
In CTLN1; unknown pathological significance.
Increased thermal stability; loss of argininosuccinate synthase activity.
Significant loss of acetylation but no decrease in enzyme activity; when associated with Q-165 or R-165.
Significant loss of acetylation but no decrease in enzyme activity; when associated with Q-176 or R-176.
High affinity cationic amino acid transporter 1
DNA polymerase alpha subunit B N-terminal
DNA polymerase alpha/delta/epsilon subunit B
In BMFS3; loss of HSPA8-binding; no effect on PA2G4-, nor on ZNF622-binding.
Zinc finger CCHC domain-containing protein 9
Localizes to cell-ECM adhesions; abolishes FLNA and FLNC interactions; failed to decorate actin filaments.
SPARC-related modular calcium-binding protein 1
Major facilitator superfamily domain-containing protein 6
Nucleolar pre-ribosomal-associated protein 1
Essential for DNA hairpin formation, participates in base-stacking interactions near the cleavage site
Found in a patient with T and B cell immunodeficiency and progressive multifocal leukoencephalopathy; unknown pathological significance.
Found in a patient with an atypical form of combined immunodeficiency; unknown pathological significance.
Found in a patient with common variable immunodeficiency with B cell deficiency; decreased recombinant activity.
In CHIDG and OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome; reduced recombination activity when associated with H-737.
In CHIDG; reduced recombination activity.
In OS and CHIDG; reduced recombination activity when associated with T-507.
In OS and T(-)B(-)NK(+) SCID; found in a patient with an atypical form of severe combined immunodeficiency/Omenn syndrome.
In OS; also found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome.
In OS; also in a patient with multiple autoimmune disorders.
In OS; found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome.
In T(-)B(-)NK(+) SCID and OS; also found in a patient with an atypical form of severe combined immunodeficiency/Omenn syndrome; decreased recombination activity.
In T(-)B(-)NK(+) SCID; also found in patients with an atypical form of severe combined immunodeficiency/Omenn syndrome; loss of recombination activity; unknown pathological significance.
In T(-)B(-)NK(+) SCID; decreased recombination activity.
In T(-)B(-)NK(+) SCID; unknown pathological significance.
In T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome.
Probable disease-associated variant found in a patient with relatively late onset of infections and isolated T-cell lymphopenia; also found in a patient with T and B cell immunodeficiency and progressive multifocal leukoencephalopathy; decreases recombination activity; no effect on protein abundance.
Probable disease-associated variant found in a patient with severe combined immunodeficiency with maternal fetal engraftment.
V(D)J recombination-activating protein 1
Nitric oxide synthase-interacting protein
Nitric oxide synthase-interacting protein zinc-finger
In L2HGA; alters protein processing and abolishes catalytic activity.
L-2-hydroxyglutarate dehydrogenase, mitochondrial
Cytidine and dCMP deaminase domain-containing protein 1
CCR4-NOT transcription complex subunit 6-like
Required for interaction with CNOT1, CNOT3 and CNOT7
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.
Dominant-negative mutant; leading to impair inhibition of SOCE.
Store-operated calcium entry-associated regulatory factor
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.
Mediates homodimerization and heterodimerization
Abolishes palmitoyltransferase activity.
Found in a patient with syndromic intellectual disability; unknown pathological significance.
In BVSYS; the mutation impairs interaction with the Mediator complex.
Mediator of RNA polymerase II transcription subunit 25
Reduced glycosylation. Abolishes glycosylation; when associated with Q-677 and Q-687.
Reduced glycosylation. Abolishes glycosylation; when associated with Q-677 and Q-697.
Reduced glycosylation. Abolishes glycosylation; when associated with Q-687 and Q-697.
Sodium-driven chloride bicarbonate exchanger
In CNM2; decreased interaction with DNM2.
In CNM2; results in severely decreased membrane tubulation.
In isoform BIN1, isoform BIN1+12A and isoform BIN1-13.
In isoform BIN1-10-13 and isoform BIN1-13.
In isoform IIB, isoform IIC2, isoform II2, isoform II3, isoform BIN1, isoform BIN1+12A, isoform BIN1-10-13 and isoform BIN1-13.
Probable disease-associated variant found in a sporadic case of centronulear myopathy; does not induce membrane tubulation in cultured cells.
In BBDS2; unknown pathological significance.
In NPHS26; unknown pathological significance.
DNA-directed RNA polymerase II subunit RPB3
DNA-directed RNA polymerase RpoA/D/Rpb3-type
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7
Trafficking protein particle complex subunit 13
In IMD49; loss of stimulation of T-lymphocyte development; dominant negative loss of activation of IL2 expression; results in reduced binding to known canonical promoters and abnormal binding to novel DNA sites not recognized by the wild-type protein; no effect on interaction with EP300.
Peptidyl-prolyl cis-trans isomerase FKBP1A
In AAT12; unknown pathological significance; has no effect on assembly of FBN1-containing microfibrils.
In AAT12; unknown pathological significance; results in impaired assembly of FBN1-containing microfibrils.
Thrombospondin type-1 domain-containing protein 4
Heat shock transcription factor, X-linked member 3
3-hydroxyacyl-CoA dehydrogenase C-terminal
3-hydroxyacyl-CoA dehydrogenase NAD binding
For hydroxyacyl-coenzyme A dehydrogenase activity
Important for hydroxyacyl-coenzyme A dehydrogenase activity
Important for long-chain enoyl-CoA hydratase activity
In AFLP and LCHAD deficiency; loss of long-chain-3-hydroxyacyl-CoA dehydrogenase activity.
In MTPD1; mild phenotype with slowly progressive myopathy and sensorimotor polyneuropathy.
Trifunctional enzyme subunit alpha, mitochondrial
Abolishes autophosphorylation, no effect on lipid kinase activity.
Abolishes autophosphorylation, reduced lipid kinase activity.
Abolishes lipid and protein kinase activities.
In IMD14A; results in gain of function causing enhanced membrane association and kinase activity.
In ROCHIS; no protein can be detected by Western blot in patient cells.
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Coiled-coil domain-containing protein 63
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
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
8 X 2 AA approximate tandem repeats of Q-P
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
Putative 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase
In ENFL3; approximately 10-fold increase in acetylcholine sensitivity.
Increases ligand activation in LS and HS nAChR subtypes.
Key residue for a rapid dissociation (K(off)) from the conotoxin BuIA
Key residue that may interfere with effective access of the conotoxin BuIA to the channel binding site
Neuronal acetylcholine receptor subunit beta-2
Induces a strong reduction in kinase activity.
5-glutamyl glycerylphosphorylethanolamine
Abolishes EEF1AKMT4-mediated methylation.
N6,N6,N6-trimethyllysine; alternate; by EEF1AKMT3
N6,N6,N6-trimethyllysine; alternate; by EEF1AKMT4
N6,N6-dimethyllysine; alternate; by EEF1AKMT4
N6-methyllysine; alternate; by EEF1AKMT4
Abolishes secretion and alters location of the protein from inside the exosome to the exosomal surface.
No effect on polymerase activity. Increases accuracy by ten-fold.
Reduces polymerase activity. No effect on accuracy.
Loss of kinase activity; when associated with T-244.
Loss of kinase activity; when associated with T-249.
MAP kinase-interacting serine/threonine-protein kinase 2
Decreases palmitoylation by 55%. Prevents palmitoylation; when associated with S-195. Targeted to Golgi and cytosol; when associated with E-42.
Increases palmitoylation. Targeted to Golgi membranes. Targeted to Golgi and cytosol; when associated with S-194. Targeted to cytosol; when associated with S-195.
Prevents farnesylation. Targeted to cytosol; when associated with E-42. Decreases palmitoylation by 13%. Prevents palmitoylation; when associated with S-194.
In one patient presenting with severe bleeding; somatic mutation; results in a non-functional channel.
Cleavage and polyadenylation specificity factor subunit 4
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.
Sufficient for association with the Arp2/3 complex
Abolishes enzyme activity. Impairs protein folding and/or stability.
Decreases enzyme activity by 87%. Impairs protein folding and/or stability.
Decreases enzyme activity by 89%. Impairs protein folding and/or stability.
Decreases enzyme activity by 90%. Strongly decreases affinity for protoporphyrinogen-IX.
Found in patients with the homozygous variant of variegate porphyria; unknown pathological significance; results in reduction of activity in a prokariotyc expression system but has normal activity when expressed in an eukaryotic system.
In VP; abolishes activity; impairs protein folding and/or stability.
In VP; abolishes enzyme activity; impairs protein folding and/or stability.
In VP; decreases enzyme activity; impairs protein folding and/or stability.
In VP; results in enzyme activity decrease; impairs protein folding and/or stability; more resistant to thermal denaturation than wild-type enzyme.
In VP; slightly decreases enzyme activity.
In VP; strongly decreases enzyme activity.
In VP; strongly decreases enzyme activity; does not affect mitochondrial protein targeting and localization.
In VP; strongly decreases enzyme activity; does not affect mitochondrial protein targeting and localization; more resistant to thermal denaturation than wild-type enzyme.
In VP; strongly decreases enzyme activity; impairs protein folding and/or stability.
In VP; strongly decreases enzyme activity; more resistant to thermal denaturation than wild-type enzyme; abolishes mitochondrial protein targeting and localization.
Rap guanine nucleotide exchange factor 4
Decreased defense response to bacterium.
In IMD77; decreased defense response to bacterium.
In IMD77; unknown pathological significance; decreased defense response to bacterium.
Macrophage-expressed gene 1 protein, processed form
In CRS5; low-penetrance mutation associated with disease susceptibility; results in gain-of-function.
Hyaluronan and proteoglycan link protein 3
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.
Transforming growth factor beta receptor type 3
Abolishes the interaction with MCM2, TONSL and histones H3.3 and H4. Disrupts the formation of the co-chaperone complex with MCM2 and histones H3.3 and H4.
Disrupts the formation of the co-chaperone complex with MCM2 and histones H3.3 and H4.
Does not affect interaction with histones.
Increased binding to histones H3 and H4. Less integration of histones H3 and H4 in chromatin. Increased recruitment of histone deposition factors to chromatin. Trapped on chromatin throughout the cell cycle in a manner depending on histone-binding. Released from chromatin trap; when associated with Ala-224; Ala-227; Ala-238 and Ala-242.
Partial loss of histone dimer H3-H4 interaction. Reduces the co-chaperone complex formation with MCM2; histone H3.3 and H4.
Partial loss of histone dimer H3-H4 interaction. Reduces the formation of the co-chaperone complex with MCM2 and histones H3.3 and H4.
Reduces the co-chaperone complex formation with MCM2; histone H3.3 and H4.
Reduces the formation of the co-chaperone complex with MCM2 and histones H3.3 and H4.
Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
Important for LPL transport to the lumenal surface of endothelial cells
In HLPP1D; a patient with chylomicronemia; no effect on protein expression at the cell surface; loss of interaction with LPL; loss of interaction with chylomicrons; promotes formation of dimers and oligomers reducing number of monomers.
In HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL.
In HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers.
In HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers.
In HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers.
In HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers.
In HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers.
In HLPP1D; unknown pathological significance; results in decreased GPIHBP1 expression; promotes formation of dimers and oligomers severely reducing number of monomers; does not affect interaction with LPL when associated in cis with F-14 in one individual.
It may act as a disease modifier preserving from severe HLPP1D when associated with R-68 or F-89; results in increased GPIHBP1 expression at the cell surface; does not affect interaction with LPL when associated in cis with R-68 in one individual.
Loss of interaction with LPL. Only slightly increased formation of dimers and oligomers. No effect on number of monomers.
No discernible effect on interaction with LPL, chylomicrons or APOA5.
Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction.
Promotes formation of dimers and oligomers reducing number of monomers.
Promotes formation of dimers and oligomers reducing number of monomers. Loss of LPL interaction.
Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL.
Promotes formation of dimers and oligomers severely reducing number of monomers.
Retained some interaction with LPL. No effect on number of monomers.
Found in a patient with azoospermia; unknown pathological significance.
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.
Inhibition of STAT1/STAT3 activity. No effect on STAT5 activity. Some loss of SOCS3 binding.
Interaction with APS and STAT5, and activation
No effect on STAT1/STAT3 nor STAT5 activity.
Required for high-affinity SOCS3 binding
In DEE55; reduced GPI-anchor biosynthetic process; may affect expression of isoform A.
Phosphatidylinositol N-acetylglucosaminyltransferase subunit P
Decreased activity toward linear ubiquitin.
Decreased affinity for linear diubiquitin.
Does not affect down-regulation of NF-kappa-B signaling.
In AIPDS and IMD107; decreased stability; impaired ability to mediate deubiquitination of linear polyubiquitin chains; loss of NF-kappa-B inhibition and increased NF-kappa-B signaling; does not affect ability to interact with RNF31.
In AIPDS and IMD107; slightly impaired ability to mediate deubiquitination of linear polyubiquitin chains; does not affect ability to interact with RNF31; severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling.
In AIPDS; decreased function in protein linear deubiquitination.
In IMD107; loss of NF-kappa-B inhibition and increased NF-kappa-B signaling.
In IMD107; severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling.
Results in strong reduction of kcat while not affecting KM.
Severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling.
Stabilizes H-339 in the active conformation, generating a more reactive enzyme.
Stabilizes H-339 in the active conformation, generating a more reactive enzyme. Severely decreased NF-kappa-B inhibition and increased NF-kappa-B signaling.
Strongly reduced interaction with RNF31.
Corticotropin-releasing factor receptor 1
In isoform CRF-R2, isoform CRF-R3 and isoform CRF-R4.
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.
Ring-like domain; necessary for ubiqitination of RIPK3
Exocyst complex component 3-like protein
Mediates interaction with EXOC2, EXOC4 and EXOC5
Loss of phosphatase activity; when associated with A-109 and with A-146.
Loss of phosphatase activity; when associated with A-109 and with A-202.
Loss of phosphatase activity; when associated with A-146 and with A-202.
Stabilizes the active site histidine for nucleophilic attack
Mesoderm induction early response protein 3
Found in a patient with features of Robinow syndrome; unknown pathological significance.
In KPTS; increased proteasomal degradation.
Tetratricopeptide repeat protein 23-like
Abolishes binding to GTP and to SEPTIN11, and also abolishes the ability of SEPTIN12 to form filamentous structures.
In SPGF10; results in significantly reduced GTP hydrolysis due to impaired GTP binding; disrupts interaction with SEPTIN7, SEPTIN6 and SEPTIN2; absence of SEPTIN12, SEPTIN7, SEPTIN6, SEPTIN2 and SEPTIN4 from the sperm annulus; disrupts interaction with LMNB1.
In SPGF10; results in significantly reduced GTP hydrolysis; disrupts interaction with SEPTIN7, SEPTIN6 and SEPTIN2; decreases interaction with SPAG4.
Self-association (via N-terminus) to polymerize octameric septin 12-7-6-2/4-2/4-6-7-12 filaments
In IGF1RES; has decreased IGF1R function.
In IGF1RES; leads to failure of processing of the IGF1R proreceptor to mature IGF1R.
In IGF1RES; significant decrease in IGF1-induced DNA synthesis and AKT1 phosphorylation in patient fibroblasts.
In IGF1RES; unknown pathological significance; significant decrease in IGF1-induced DNA synthesis; significant increase in IGF1-induced AKT1 phosphorylation in patient fibroblasts.
In a renal chromophobe sample; somatic mutation.
Insulin-like growth factor 1 receptor alpha chain
Insulin-like growth factor 1 receptor beta chain
Kinase inactive. Abolishes tyrosine phosphorylation and abolishes interaction with IRS1, SHC1 and PIK3R1.
Reduces tyrosine phosphorylation. Abolishes interaction with IRS1 and SHC1. Does not abolish interaction with PIK3R1, nor with GRB10.
In RDEOA; unknown pathological significance.
RCC1 and BTB domain-containing protein 1
Found in a child with developmental disabilities; unknown pathological significance.
SH3 and multiple ankyrin repeat domains protein 2
1-acyl-sn-glycerol-3-phosphate acyltransferase alpha
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.
Serine/threonine-protein phosphatase 4 regulatory subunit 4
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.
Formyltetrahydrofolate synthetase domain
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.
Methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (D/C) domain
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.
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
E3 ubiquitin-protein ligase RBX1, N-terminally processed
N-acetylalanine; in E3 ubiquitin-protein ligase RBX1, N-terminally processed
Strong reduction in ligase activity; when associated with A-53.
Strong reduction in ligase activity; when associated with A-56.
Strong reduction in ligase activity; when associated with A-75.
Strong reduction in ligase activity; when associated with A-77.
In GLC1O; also found in patients with normal pressure glaucoma; unknown pathological significance; impaired ligand-mediated TRKB signaling and reduced neurite outgrowth.
In GLC1O; unknown pathological significance.
Nucleosome-remodeling factor subunit BPTF
Strongly reduces binding to histone H3K4me3.
Required for Wnt-signaling inhibition and LRP6 degradation
Transmembrane protein 131-like conserved
BTB/POZ domain-containing protein KCTD17
In DYT26; does not affect cytoplasmic subcellular location.
In HTX9; the mutant protein is undetectable in respiratory cilia from an affected patient.
Meiosis-specific nuclear structural protein 1
Loss of predominant localization in the nucleus; when associated with A-186. No effect on CAD- ANDHSPA5-binding; when associated with A-186.
Loss of predominant localization in the nucleus; when associated with A-187. No effect on CAD- ANDHSPA5-binding; when associated with A-187.
Affects binding to importins alpha, including KPNA2, hence may affect import to the nucleus.
Associated with LYNCH2; no effect on MLH1 splicing.
Associated with LYNCH2; results in partial MLH1 exon 10 skipping on ex vivo splicing assay; decreased mismatch repair activity.
Can be associated with HNPCC in some populations.
Found in an endometrial cancer sample; somatic mutation.
In CRC; sporadic; somatic mutation; unknown pathological significance.
In CRC; sporadic; susceptibility to; ATPase function attenuated but not eliminated.
In CRC; unknown pathological significance.
In HNPCC; unknown pathological significance.
In LYNCH2 and CRC; abrogates interaction with EXO1; no decrease in mismatch repair activity.
In LYNCH2 and CRC; unknown pathological significance; no decrease in mismatch repair activity; no effect on nuclear localization.
In LYNCH2 and MMRCS1; abrogates interaction with EXO1; loss of protein expression; loss of nuclear localization; no effect on MLH1 splicing.
In LYNCH2; also found in an endometrial cancer sample; no effect on MLH1 splicing.
In LYNCH2; also found in sporadic colorectal cancer.
In LYNCH2; decreased mismatch repair activity.
In LYNCH2; decreased mismatch repair activity; defective in interaction with PMS2 and EXO1; loss of protein expression; may lose nuclear localization.
In LYNCH2; decreased mismatch repair activity; defective in interaction with PMS2.
In LYNCH2; decreased mismatch repair activity; defective in interaction with PMS2; loss of protein expression; loss of nuclear localization.
In LYNCH2; decreased mismatch repair activity; loss of interaction with PMS2 and EXO1; loss of protein expression; may lose nuclear localization.
In LYNCH2; decreased mismatch repair activity; loss of nuclear localization.
In LYNCH2; decreased mismatch repair activity; loss of nuclear localization; normal interaction with PMS2.
In LYNCH2; decreased mismatch repair activity; loss of protein expression.
In LYNCH2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization.
In LYNCH2; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization; no effect on MLH1 splicing.
In LYNCH2; decreased mismatch repair activity; no effect on MLH1 splicing; fails to interact with PMS2 and EXO1; loss of nuclear localization.
In LYNCH2; decreased mismatch repair activity; no effect on nuclear localization.
In LYNCH2; decreased mismatch repair activity; normal interaction with PMS2; loss of protein expression; loss of nuclear localization.
In LYNCH2; defective in interaction with PMS2 and EXO1; no decrease in mismatch repair activity.
In LYNCH2; interacts only very weakly with PMS2; abrogates interaction with EXO1; decreased mismatch repair activity; may lose nuclear localization.
In LYNCH2; loss of nuclear localization.
In LYNCH2; loss of protein expression; loss of nuclear localization.
In LYNCH2; loss of protein expression; normal interaction with PMS2 and EXO1; decreased mismatch repair activity; no effect on nuclear localization.
In LYNCH2; no decrease in mismatch repair activity.
In LYNCH2; no effect on MLH1 splicing; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization.
In LYNCH2; no effect on MLH1 splicing; loss of mismatch repair activity.
In LYNCH2; requires 2 nucleotide substitutions; decreased mismatch repair activity.
In LYNCH2; results in partial MLH1 exon 10 skipping on ex vivo splicing assay; decreased mismatch repair activity; no effect on nuclear localization.
In LYNCH2; results in weak MLH1 exon 11 skipping on ex vivo splicing assay; decreased mismatch repair activity; loss of protein expression; loss of nuclear localization.
In LYNCH2; the protein is unstable; loss of nuclear localization; loss of protein expression; no decrease in mismatch repair activity.
In LYNCH2; type I; abrogates interaction with EXO1.
In LYNCH2; type II; decreased mismatch repair activity.
In LYNCH2; type II; loss of nuclear localization.
In LYNCH2; unknown pathological significance.
In LYNCH2; unknown pathological significance; acts functionally like the wild-type protein.
In LYNCH2; unknown pathological significance; also found in lobular carcinoma in situ of the breast; no effect on MLH1 splicing.
In LYNCH2; unknown pathological significance; defective in interaction with PMS2 and EXO1; may lose nuclear localization; loss of protein expression; no decrease in mismatch repair activity.
In LYNCH2; unknown pathological significance; no decrease in mismatch repair activity.
In LYNCH2; unknown pathological significance; no decrease in mismatch repair activity; no effect on nuclear localization.
In LYNCH2; unknown pathological significance; no effect on MLH1 splicing.
In LYNCH2; unknown pathological significance; no effect on nuclear localization; normal interaction with PMS2 and EXO1.
In LYNCH2; unknown pathological significance; requires 2 nucleotide substitutions; interacts weakly with PMS2; no decrease in mismatch repair activity; no effect on nuclear localization.
In MMRCS1; requires 2 nucleotide substitutions.
In gastric cancer; unknown pathological significance.
No decrease in mismatch repair activity; no effect on nuclear localization.
Normal interaction with PMS2; no decrease in mismatch repair activity; no effect on nuclear localization.
Mitogen-activated protein kinase kinase kinase kinase 3
Abolishes interaction with LDLRAP1 and ARRB1. Greatly reduces DENND1B-binding.
Beta-adaptin appendage C-terminal subdomain
Clathrin adaptor alpha/beta/gamma-adaptin appendage Ig-like subdomain
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.
Abolished NAD-dependent protein deacetylase, deacylase and mono-ADP-ribosyltransferase activities. Impaired ability to recognize and bind double-strand breaks (DSBs) sites.
Abolished NAD-dependent protein deacetylase, defatty-acylase and mono-ADP-ribosyltransferase activities.
Abolishes ability to promote DNA repair and recruit PARP1 to double-strand breaks (DSBs).
Does not affect ability to promote DNA repair.
Does not affect histone deacetylase activity.
Does not affect the NAD-dependent protein defatty-acylase activity. Abolished NAD-dependent protein deacetylase and mono-ADP-ribosyltransferase activities.
Does not affect the mono-ADP-ribosyltransferase activity. Abolished NAD-dependent protein deacetylase and defatty-acylase activities.
Formation of an covalent adduct with nitro-fatty acid activators
Found in a family presenting with four cases of perinatal lethality caused by severe neurodevelopmental and cardiac anomalies; abolished histone deacetylase activity; abolished protein demyristoylase activity; decreased ability to recognize and bind double-strand breaks (DSBs) sites; does not affect nuclear localization.
Found in cervical cancer; somatic mutation; reduced histone deacetylase activity; slightly reduced the protein-lysine demyristoylase activity.
Found in kidney cancer; somatic mutation; reduced histone deacetylase activity; does not affect the protein-lysine demyristoylase activity.
Found in melanoma; somatic mutation; reduced histone deacetylase activity; does not affect the protein-lysine demyristoylase activity.
Found in non-small cell lung cancer; somatic mutation; does not affect ability to recognize and bind double-strand breaks (DSBs) sites; strongly reduced histone deacetylase activity; strongly reduced the protein-lysine demyristoylase activity.
Found in non-small cell lung cancer; somatic mutation; reduced histone deacetylase activity; does not affect the protein-lysine demyristoylase activity.
Found in non-small cell lung cancer; somatic mutation; reduced localization to chromatin.
Found in non-small cell lung cancer; somatic mutation; reduced localization to chromatin; reduced histone deacetylase activity; does not affect the protein-lysine demyristoylase activity.
Found in non-small cell lung cancer; somatic mutation; reduced localization to chromatin; strongly reduced histone deacetylase activity; strongly reduced the protein-lysine demyristoylase activity.
In 4KR mutant; abolished sumoylation, leading to increased H3K56ac; when associated with 296-R--R-300 and R-316.
In 4KR mutant; abolished sumoylation, leading to increased H3K56ac; when associated with 296-R--R-300 and R-332.
In 4KR mutant; abolished sumoylation, leading to increased H3K56ac; when associated with R-316 and R-332.
In AAA mutant; strongly decreased nucleosome-binding; when associated with 206-A--A-208.
In AAA mutant; strongly decreased nucleosome-binding; when associated with A-45.
Increased protein-lysine demyristoylase activity.
Mimics acetylation, leading to impaired ability to recognize and bind double-strand breaks (DSBs) sites.
Mimics phosphorylation; increased ability to promote DNA repair and recruit PARP1 to double-strand breaks (DSBs).
NAD-dependent protein deacylase sirtuin-6
Reduced MDL-800 and MDL-801 compounds-binding.
Slightly reduced MDL-800 and MDL-801 compounds-binding.
Strongly reduced MDL-800 and MDL-801 compounds-binding.
30 X 6 AA repeats of K-S-P-[AEPV]-[EAK]-[AEVK]
Confers susceptibility to neuroblastoma.
Confers susceptibility to neuroblastoma; found as germline mutation in a neuroblastoma family.
Leucine-rich single-pass membrane protein 2
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.
Abolishes enzymatic activity. Increased interaction with diubiquitin.
Decreased interaction with diubiquitin. No accumulation of free diubiquitin. Decreased levels of polyubiquitinated lysozyme.
Interaction with ubiquitin. Crossover loop which restricts access of large ubiquitin adducts to the active site
Ubiquitin carboxyl-terminal hydrolase family 1 cysteine active-site
Ubiquitin carboxyl-terminal hydrolase isozyme L3
ADP/ATP translocase 3, N-terminally processed
N-acetylthreonine; in ADP/ATP translocase 3, N-terminally processed
Sperm-associated microtubule inner protein 4
Probable crossover junction endonuclease EME2
Does not affect ISG15 signaling, interaction with ITGAL or activation of SRC family tyrosine kinases.
Interchain (with C-87 in UBE2N); alternate
Involved in the ligation of specific target proteins
Reduces ISG15 signaling. Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases; when associated with D-102.
Reduces ISG15 signaling. Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases; when associated with L-96.
Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases.
Strongly reduces ISG15 signaling and abolishes interaction with ITGAL.
In NEDMHAL; unknown pathological significance; results in impaired proteasome assembly.
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.
Cilia- and flagella-associated protein 95
Kelch repeat and BTB domain-containing protein 6
Loss of interaction with CUL3. Loss of function in TIAM1 ubiquitination and degradation.
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.
Catalytic inactive mutant for both ADP-sugar pyrophosphatase and nuclear ATP-synthesis activities. Reduces catalytic rate 6300-fold.
Impaired phosphorylation; generates ATP in the presence of diphosphate.
Phosphomimetic mutant; unable to generate ATP in the presence of diphosphate.
Reduces affinity for substrate about 15-fold and reduces catalytic rate about 17-fold.
Reduces affinity for substrate about 5-fold and reduces catalytic rate 67-fold.
Reduces affinity for substrate about 6-fold.
Reduces affinity for substrate about 6-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-28.
Reduces affinity for substrate about 8-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-46.
Interaction with the C-terminus of NDC80 and the SPBC24-SPBC25 subcomplex
Interaction with the N-terminus of NDC80
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.
Constitutive coactivator of PPAR-gamma-like protein 2
Found in a patient with Leber congenital amaurosis.
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.
ATP synthase membrane subunit K, mitochondrial
Neuroblastoma breakpoint family member 6
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.
Required for ADAM17-mediated proteolysis
Required for endocytosis and down-regulation
Coiled-coil domain-containing protein 170
Required for binding to microtubules and Golgi apparatus location
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 IIFNs.
In VRV mutant; abolished binding to membranes and lipidation to ATG8 family proteins.
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.
In MITCH; gain-of-function; increased dimerization; increased protein levels and peroxisomal acyl-coenzyme A oxidase function; increased levels of reactive oxygen species; no effect on VLCFA levels; no effect on peroxisome location; causes Schwann cell death and myelination defects.
In Pseudo-NALD; unknown pathological significance.
Abolishes interaction with HOXB-AS3 peptide; when associated with A-218 and A-225.
Abolishes interaction with HOXB-AS3 peptide; when associated with A-218 and A-232.
Abolishes interaction with HOXB-AS3 peptide; when associated with A-225 and A-232.
Heterogeneous nuclear ribonucleoprotein A1
Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed
In ALS20; increases subcellular localization of HNRNPA1 in cytoplasmic inclusions with stress granules.
In ALS20; unknown pathological significance.
N-acetylserine; in Heterogeneous nuclear ribonucleoprotein A1, N-terminally processed
Meiotic recombination protein DMC1/LIM15 homolog
Abolishes homodimerization and nuclear localization. Abolishes homodimerization, multimerization, nuclear localization, and DNA binding activity; when associated with A-604-A-A-605. Abolishes interaction with SUMO1 and reduces sumoylation of CHD3/Mi2-alpha; when associated with 604-A-A-605.
Abolishes homodimerization, multimerization, interaction with KPNB1, nuclear localization and DNA binding activity. Abolishes interaction with SUMO1 and reduces SUMOylation of CHD3/Mi2-alpha.
Abolishes nuclear localization, however has no effect on homodimerization; when associated with A-530-A-A-531.
Abolishes nuclear localization, however has no effect on homodimerization; when associated with A-534.
No effect on homodimerization or nuclear localization.
Reduces homodimerization and nuclear localization. Abolishes homodimerization, multimerization, nuclear localization, and DNA binding activity; when associated with A-600-A-A-601. Abolishes interaction with SUMO1 and reduces sumoylation of CHD3/Mi2-alpha; when associated with A-600-A-A-601.
Required for interaction with human adenovirus early E1A protein
Required for nuclear localization and homodimerization
Required for the formation of higher order complexes of ZBED1 with consensus DNA binding sequences
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.
Ubiquitin carboxyl-terminal hydrolase 46
In POBINDS; associated in cis with C-86.
In POBINDS; unknown pathological significance; associated in cis with 5-E--R-215 del.
No effect on interaction alpha subunit CSNK2A1. Loss on interaction with ARK2N and Epstein-Barr virus EBNA1.
In ARGIN; decreases erythrocyte arginase activity.
Abrogates sumoylation. Abolished sumoylation by PIAS4, promoting interaction with PRKDC, leading to decreased repair of DNA double-strand breaks (DSBs) via homologous recombination (HR).
Decreased autoacetylation; leading to decreased acetyltransferase activity and ability to acetylate FOXP3.
Does not affect phosphorylation; when associated with A-254.
Does not affect phosphorylation; when associated with A-257.
Impaired acetylation, leading to reduced histone acetyltransferase activity. In K6R; abolished autoacetylation; when associated with R-120, R-148, R-150, R-187 and R-189.
In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-150 and R-187.
In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-150 and R-189.
In K6R; abolished autoacetylation; when associated with R-104, R-120, R-148, R-187 and R-189.
In K6R; abolished autoacetylation; when associated with R-104, R-120, R-150, R-187 and R-189.
In K6R; abolished autoacetylation; when associated with R-104, R-148, R-150, R-187 and R-189.
In KAT5(QG/EE) mutant; abolished acetyltransferase activity. Impaired ability to activate CGAS.
In NEDFASB; decreased histone acetyltransferase activity.
Loss of function. Does not affect phosphorylation.
Mimics acetylation; promoting interaction with FOXP3 and subsequent acetylation.
Mimics phosphorylation, promoting protein acetyltransferase activity.
Reduced phosphorylation, leading to reduced protein acetyltransferase activity. Abolishes phosphorylation; when associated with A-86. Reduced histone acetyltransferase activity. Abolished phosphorylation by GSK3 at S-86.
Reduced phosphorylation. Abolishes phosphorylation; when associated with A-90. Reduced histone acetyltransferase activity. Abolished phosphorylation by GSK3 and decreased acetyltransferase activity.
In CMNS and colorectal cancer; somatic mutation.
In CMNS, NCMS, KNEN and NMTC2; also found in lung carcinoma cell and melanoma; impaired GTP hydrolysis activity, trapping NRAS in a constitutive GTP-bound active conformation; promotes melanomagenesis.
In N-Ras-2KR mutant; decreased fatty-acylation.
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.
SH3 domain-containing YSC84-like protein 1
In NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; decreased interaction with tubulin beta.
In NMIHBA; loss of function in regulation of cell proliferation and migration; loss of function in neurogenesis; impaired regulation of microtubule polymerization; increased phosphatase activity; no effect on interaction with tubulin beta.
In NMIHBA; unknown pathological significance.
No change in cAMPPDE activity. Partial loss of cAMPPDE activity; when associated with D-28. Partial loss of cAMPPDE activity; when associated with D-28 and D-179.
Partial loss of cAMPPDE activity. Partial loss of cAMPPDE activity; when associated with D-106. Partial loss of cAMPPDE activity; when associated with D-106 and D-179.
Partial loss of cAMPPDE activity. Partial loss of cAMPPDE activity; when associated with D-28 and D-106.
In ODG7; unknown pathological significance.
Hairy and enhancer of split-related protein HELT
Decreased diacylglycerol kinase activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol.
Decreased protein abundance and diacylglycerol kinase activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol.
Loss of diacylglycerol kinase activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol.
Impairs binding to S-adenosyl-L-methionine. Significantly reduces N-methyltransferase activity.
Significantly reduces N-methyltransferase activity.
No effect on already low affinity binding to trehalose-6,6'-dimycolate.
Major binding site for inhibitory zinc or copper
Epithelial splicing regulatory protein 2
Reduces interaction with AURKA; when associated with A-28.
Reduces interaction with AURKA; when associated with A-29.
Reduces interaction with AURKA; when associated with A-35.
Reduces interaction with AURKA; when associated with A-36.
Osteoclast stimulatory transmembrane protein
Iroquois-class homeodomain protein IRX-1
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.
In SRXY6; unknown pathological significance.
Mitogen-activated protein kinase kinase kinase 1
Mitochondrial import receptor subunit TOM5 homolog
Abolishes proteolytic cleavage; when associated with 119-A-A-120.
Abolishes proteolytic cleavage; when associated with A-437.
C-Jun-amino-terminal kinase-interacting protein 3
In NEDBA; affects axon development when expressed in a heterologous system.
In NEDBA; unknown pathological significance.
JNK-binding domain (JBD); essential for its function in axon elongation
Kinesin-binding domain (KBD); essential for its function in axon elongation
Leucine zipper-like domain (LZ); essential for its function in axon elongation
Golgin subfamily A member 6-like protein 2
In isoform 1, isoform 4, isoform 5 and isoform 6.
Sterile alpha motif domain-containing protein 11
Golgi-resident adenosine 3',5'-bisphosphate 3'-phosphatase
Abolishes interaction with SIAH1; when associated with N-64.
Abolishes interaction with SIAH1; when associated with N-66.
In CILD11; unknown pathological significance.
Abolishes binding to telomeric 5'-TTAGGG-3' motif.
Abolishes binding to telomeric 5'-TTAGGG-3' motif. Confers binding to the non-telomeric 5'-GTGAGT-3' motif.
Critical for recognition and binding of 5'-TTAGGG-3' motifs in telomeric DNA
Impairs binding to telomeric 5'-TTAGGG-3' motif.
Has no impact on the affinity for HLA-E.
In VRJS; loss of function mutation; results in altered dosage of different PUF60 protein forms and abnormal splicing profile of several target genes.
Inhibits transcriptional repression, interaction with ERCC3 and apoptosis induction
Myb-related transcription factor, partner of profilin
Zinc finger BED domain-containing protein 6
Long-chain fatty acid transport protein 2
ATP-binding cassette sub-family C member 8
In HHF1; altered intracellular trafficking.
In HHF1; cannot form a functional channel, due to protein instability or defective transport to the membrane.
In HHF1; channels insensitive to metabolic inhibition and to activation by ADP.
In HHF1; does not alter surface expression but channels are not functional.
In HHF1; highly decreases cell membrane expression; highly reduced traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide.
In HHF1; mild; dominantly inherited; channels insensitive to metabolic inhibition and to activation by ADP.
In HHF1; modest impairment of channel function.
In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide.
In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; reduced potassium channel response to activators such as MgADP or to diazoxide.
In HHF1; reduced channels surface expression and response to ADP.
In HHF1; severe; high frequency in Ashkenazi Jewish patients; defective trafficking and lack of surface expression.
In HHF1; severe; high prevalence in Finland; loss of channel activity.
In HHF1; severe; loss of channel activity.
In LIH; partially impairs ATP-dependent potassium channel function.
In PNDM3; highly reduced inhibition by ATP when associated with I-229.
In PNDM3; highly reduced inhibition by ATP when associated with L-1523.
In PNDM3; slightly reduced inhibition by ATP.
In PNDM3; with neurologic features; reduces the sensitivity of the K(ATP) channel to inhibition by MgATP; increases whole-cell K(ATP) current.
Cysteine-rich hydrophobic domain-containing protein 1
Decreased palmitoylation; decreased localization to the plasma membrane; decreased stability.
Found in patients with alcohol-responsive myoclonus-dystonia; unknown pathological significance; the mutation does not affect functional properties.
May be associated with a higher risk for schizophrenia.
No effect on palmitoylation; no effect on localization to the plasma membrane.
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.
Cleavage; by factor Xa, factor XIIa, factor IXa, or thrombin
Complete loss of O-glycosylation and O-xylosylation by POGLUT1.
In FA7D; exhibits no procoagulant activity and is unable to bind tissue factor.
In FA7D; reduces tissue factor binding; impairs activation by factor Xa; abolishes amidolytic and coagulant activities.
In FA7D; results in severely impaired protein secretion.
May be associated with decreased susceptibility to myocardial infarction.
No effect on O-glycosylation by POGLUT1. Drastic decrease in O-xylosylation.
Abolished phosphorylation at Tyr-232 by isoform 1 of CHKA (CHKalpha2).
Abolishes Monooxygenase activity and impairs ability to control docking and fusion of exocytic carriers.
In MICAL-3NLSMut; abolishes nuclear localization.
Strongly reduces palmitoylation. Abolishes palmitoylation and Golgi localization; when associated with A-69.
Strongly reduces palmitoylation. Abolishes palmitoylation and Golgi localization; when associated with A-72.
In DDISBA; affects function in neuronal axonal growth; decreased ankyrin binding; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; decreased interaction with SPTAN1; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; forms cytosolic aggregates; decreased interaction with SPTAN1; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; forms cytosolic aggregates; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; increased F-actin binding; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; no effect on F-actin binding; disturbs cytoskeleton organization and dynamics.
In DDISBA; affects function in neuronal axonal growth; reduced F-actin binding; disturbs cytoskeleton organization and dynamics.
In DDISBA; disturbs cytoskeleton organization and dynamics.
In DDISBA; distursb cytoskeleton organization and dynamics.
In DDISBA; unknown pathological significance.
DNA-directed RNA polymerase III subunit RPC1
In WDRTS; 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.
(3S)-3-hydroxyasparagine; by HIF1AN; partial
Cleavage (when cotranslationally processed)
Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-923.
Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-932.
Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-923 and A-932.
Decreased phosphorylation by IKBKB/IKKB and decreased generation of the NF-kappa-B p50 subunit from p105.
Fails to promote HIF1AN-dependent 2-oxoglutarate decarboxylation.
Prevents p105 proteolysis in response to TNF-alpha.
Suppresses S-nitrosylation-induced inhibition of DNA-binding activity. Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine-induced inhibition of DNA-binding activity.
Zinc finger and SCAN domain-containing protein 22
Abolishes interaction with CYP1A1 and CYP3A4.
Membrane-associated progesterone receptor component 1
Loss of inositol 4-phosphatase activity. Alters TFRC distribution and delays TF recycling.
No effect on lack of functional expression.
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.
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.
Activity is about 26% of that of the wild-type.
In MCPH27; increased aggregation; changed nuclear envelope organization.
May be a risk factor for partial acquired lipodystrophy.
Oxysterol-binding protein-related protein 6
Arachidonate 5-lipoxygenase-activating protein
Decreased affinity for the inhibitor MK-591.
Increased affinity for the inhibitor MK-591.
Strongly decreased affinity for the inhibitor MK-591.
Strongly increased affinity for the inhibitor MK-591.
Coiled-coil domain-containing protein 121
Single-pass membrane and coiled-coil domain-containing protein 1
Hydrophobic barrier that decreases the speed of ligand binding and dissociation
Increased ability of hallucinogens to desensitize the receptor.
Loss of interaction with PATJ, CASK, APBA1, DLG1 and DLG4.
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.
In DEE89; unknown pathological significance.
In DEE89; unknown pathological significance; no effect on protein abundance; no effect on splicing.
Eliminates putative kinase activity; when associated with A-385.
Eliminates putative kinase activity; when associated with A-389.
General transcription factor IIF subunit 1
Loss of interaction with ZNF289/ARFGAP2.
CB1 cannabinoid receptor-interacting protein 1
Abolishes interaction with PRKDC and its recruitment to sites of DNA damage.
X-ray repair cross-complementing protein 5
Putative ribosome-binding factor A, mitochondrial
Ubiquitin-associated and SH3 domain-containing protein A
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
Impaired interaction with EPC1. Abolished interaction with EPC1; when associated with 259-G--G-263.
Impaired interaction with EPC1. Abolished interaction with EPC1; when associated with G-236.
Impaired interaction with EPC1; when associated with 259-D--D-263.
Impaired interaction with EPC1; when associated with D-236.
Cell surface glycoprotein CD200 receptor 1
Cysteine and histidine-rich domain-containing protein 1
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.
Disintegrin and metalloproteinase domain-containing protein 28
Loss of subcellular location at the nuclear envelope.
No effect on subcellular location at the nuclear envelope.
Protein mono-ADP-ribosyltransferase PARP11
Loss of prenylation and membrane localization.
Type II inositol 1,4,5-trisphosphate 5-phosphatase
Beta-galactoside alpha-2,6-sialyltransferase 1
No effect on dimerization and on location at the Golgi stack.
Abolishes interaction with STX6. No effect on early endosome location.
Bridge-like lipid transfer protein family member 3B
Complete loss of interaction with Lassa virus protein GPC.
Lysosome-associated membrane glycoprotein 1
N-linked (GlcNAc...) (polylactosaminoglycan) asparagine
Leukocyte immunoglobulin-like receptor subfamily B member 4
No significant change in APOE-mediated activation of LILRB4.
Required for APOE-mediated activation of LILRB4
Significant reduction in APOE-mediated activation of LILRB4.
Coiled-coil domain-containing protein 60
In HKPX4; severely decreased ATAD1 mRNA expression in lymphoblastoid cells derived from the patient compared to an unaffected control.
In HKPX4; unknown pathological significance; likely affects splicing due to removal of the splice donor site of intron 2.
Outer mitochondrial transmembrane helix translocase
In LPI; failed to induce cationic amino acid transport activity.
In LPI; failed to induce sodium-independent cationic amino acid and sodium-dependent neutral amino acid transport activity.
In LPI; failed to induce sodium-independent cationic amino acid and sodium-dependent neutral amino acid transport activity; does not affect heterodimerization with SLC3A2; affects expression level.
In LPI; moderately reduced cationic amino acid transport activity.
Complete loss of PCNA binding and of degradation after UV irradiation.
Complete loss of PCNA binding; when associated with 10-AA-11.
Complete loss of PCNA binding; when associated with A-7.
Decreased PCNA binding. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Q-4 and Y-10. Increased stability following UV irradiation and no trough during S phase; when associated with A-16 and A-17.
Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-16.
Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-17.
No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Q-4. No effect on PCNA binding, but normal degradation after UV irradiation with Q-4 and A-15.
No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Y-10. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Y-10 and A-15.
No effect on ubiquitination. Loss of ubiquitination, when associated with R-15, R-25, R-74 and R-89.
No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-74.
No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-89.
No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-74 and R-89.
No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-25, R-74 and R-89.
PCNA-interaction protein motif (PIP box)
Strongly increased stability following UV irradiation; when associated with A-8.
Strongly increased stability following UV irradiation; when associated with A-9.
Endoplasmic reticulum resident protein 44
Has no effect on interaction with RALGAPB but causes loss of activity.
In NEDHRIT; undetectable protein expression.
Ral GTPase-activating protein subunit alpha-1
Found in a patient with very early onset inflammatory bowel disease; unknown pathological significance; no effect on subcellular location; significantly reduced basal and phorbol ester-stimulated ROS generation, which may decrease resistance to infection by enteric pathogens, such as Campylobacter jejuni.
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.
Abolished N-myristoylation and subsequent palmitoylation.
Abolished palmitoylation and recruitment to lysosomes, leading to impaired activation of the mTORC1 complex.
Does not affect interaction with RRAGA and RRAGC in vitro.
Does not affect interaction with ZDHHC3.
Impaired assembly of the Ragulator complex.
Impaired recruiment of Rag GTPases (RRAGA and RRAGC) to the lysosomal membrane.
Increases translational pausing of its own mRNA.
Inhibits HM13/SPP-mediated degradation of XBP1; when associated with L-197; L-199 and L-200.
Inhibits HM13/SPP-mediated degradation of XBP1; when associated with L-197; L-199 and L-203.
Inhibits HM13/SPP-mediated degradation of XBP1; when associated with L-197; L-200 and L-203.
Inhibits HM13/SPP-mediated degradation of XBP1; when associated with L-199; L-200 and L-203.
Necessary for the translational pausing of its own mRNA
Nuclear localization signal (NLS); in isoforms 1 and isoform 2
Reduces endoplasmic reticulum localization of its own mRNA; when associated with D-198 and E-205.
Reduces endoplasmic reticulum localization of its own mRNA; when associated with E-189 and D-196.
Reduces endoplasmic reticulum localization of its own mRNA; when associated with E-189 and E-193.
Reduces endoplasmic reticulum localization of its own mRNA; when associated with E-193 and D-196.
Reduces endoplasmic reticulum localization of its own mRNA; when associated with E-194 and D-198.
Reduces endoplasmic reticulum localization of its own mRNA; when associated with E-194 and E-205.
Reduces translational pausing, membrane targeting and cytoplasmic splicing of its own mRNA.
X-box-binding protein 1, cytoplasmic form
Cytosolic 10-formyltetrahydrofolate dehydrogenase
Loss of phosphopantetheinylation by AASDHPPT. Loss of formyltetrahydrofolate dehydrogenase activity.
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.
High-affinity association with the preproteasome
G protein-regulated inducer of neurite outgrowth 3
Diminishes gap activity towards G(i)-alpha3 and autophagy in colon cancer cells.
Decreased acetylation; promotes interaction with AKT1 and PHLPP1; when associated with R-155.
Decreased acetylation; promotes interaction with AKT1 and PHLPP1; when associated with R-28.
Mimics acetylation; impaired interaction with AKT1 and PHLPP1; when associated with Q-155.
Mimics acetylation; impaired interaction with AKT1 and PHLPP1; when associated with Q-28.
Peptidyl-prolyl cis-trans isomerase FKBP5
Loss of the ability to decrease intracellular reactive oxygen species.
N-terminal domain; may mediate the alkylhydroperoxide reductase activity
Coiled-coil domain-containing protein 73
Multiple epidermal growth factor-like domains protein 8
Cilia- and flagella-associated protein 57
Rare variant found in a patient with Van der Woude syndrome; unknown pathological significance.
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
LYR motif; required for interaction with HSC20
Probable cytosolic iron-sulfur protein assembly protein CIAO1
Abolishes interaction with ETV5. Abolished repression activity.
Abolishes interaction with ETV5. No effect on repression activity.
Does not increase dopamine transporter activity. Impairs kinase activity.
Does not rescue inhibition of O-glycosylation in MAPK15-depleted cells; when associated with A-175.
Impairs chromatin binding; when associated with A-390. Increases kinase activity; when associated with A-390.
Impairs chromatin binding; when associated with A-398. Increases kinase activity; when associated with A-398.
Impairs interaction with GABARAP and MAP1LC3B. Affects subcellular localization in autophagosome. Does not induce autophagy.
Impairs interaction with PCNA. Associates with chromatin.
Loss of autophosphorylation and activity. Does not increase dopamine transporter activity. Impairs kinase activity. Does not rescue cilium assembly in MAPK15-depleted cells.
Loss of autophosphorylation and activity. Heavily phosphorylated at Thr-175.
Loss of autophosphorylation and activity. Still heavily phosphorylated at Tyr-177. Does not rescues inhibition of O-glycosylation in MAPK15-depleted cells; when associated with F-177.
Markedly decreases interaction with ESRRA. Impairs interaction with ESRRA; when associated with A-265 and 268-A--A-269. Loses the ability to re-localize ESRRA to the cytoplasm. Does not affect subcellular location in cytoplasm in presence of ESRRA.Loses the ability to repress ESRRA transcriptional activity.
Markedly decreases interaction with ESRRA. Impairs interaction with ESRRA; when associated with A-281 and 284-A--A-285. Loses the ability to re-localize ESRRA to the cytoplasm. Does not affect subcellular location in cytoplasm in presence of ESRRA. Loses the ability to repress ESRRA transcriptional activity.
Necessary to interact with ESRRA, to regulate its subcellular localization and to inhibit its transcriptional activity
Not phosphorylated at Thr-175 and Tyr-177.
PXXXP motif; regulates binding with chromatin and interaction with PCNA
Requires for interaction with GABARAP, MAP1LC3B AND GABARAPL1
Unable to induce the formation of autophagosomal structures. Is able to bind to MAP1LC3B and to colocalize with this protein to autophagosomal structures. Does not induce phosphorylation by methyl methanesulfonate. Loas of phosphorylation. Dominant negative mutant. Not phosphorylated at Thr-175 and Tyr-177.
In NS9; unknown pathological significance.
Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 519-R--A-522.
Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 551-R--A-554.
Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-419.
Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-426.
Abolishes DNA primase activity, while it increases DNA polymerase activity.
Abolishes DNA primase and polymerase activities.
In AxA; abolished DNA primase and polymerase activities.
In MYP22; reduced DNA polymerase and DNA primase activities; reduced DNA-binding.
In mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with G-419.
In mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with Y-426.
Important for interaction with IL11RA and for the stimulation of cell proliferation
Important for interaction with IL6ST and for the stimulation of cell proliferation
Increases affinity for IL11RA and stimulation of cell proliferation.
Strongly increases affinity for IL11RA and stimulation of cell proliferation.
Reduced phosphorylation by CAK and reduced kinase activity.
In CPSFS1A; unknown pathological significance.
In DA2B3; unknown pathological significance.
Improved mitochondrial targeting sequence (MTS), leading to increased import into mitochondria.
In GAMOS10; decreased formation of tRNA threonylcarbamoyladenosine modification.
In GAMOS10; slightly decreased formation of tRNA threonylcarbamoyladenosine modification.
In HHT5; impaired protein processing and function.
Loss of colocalization with SV40-induced foci upon SV40 invection.
CMT1A duplicated region transcript 15 protein-like protein
In IMD100; results in increased 2'-5'-oligoadenylate synthetase activity leading to increased RNase L-mediated cellular RNA degradation, translational arrest and apoptosis.
Loss of activity; when associated with A-331 and A-332.
Loss of activity; when associated with A-331 and A-333.
Loss of activity; when associated with A-332 and A-333.
Loss of activity; when associated with A-75.
Loss of activity; when associated with A-77.
Not prenylated and diffusely distributed. Loss of antiviral activity.
Abolished interaction with G3BP1 and ability to inhibit stress granule formation.
Abolishes deubiquitinating activity and ability to deubiquitinate 40S ribosomal proteins.
Abolishes phosphorylation by ATM; when associated with A-337.
Abolishes phosphorylation by ATM; when associated with A-42.
Decreased but not abolished interaction with G3BP1.
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
Completely abolishes the interaction with protein phosphatase 1.
Protein phosphatase 1 regulatory subunit 7
Severely impaired the binding of protein phosphatase 1.
Severely impairs the binding of protein phosphatase 1.
U2A'/phosphoprotein 32 family A C-terminal
Cation channel sperm-associated auxiliary subunit TMEM262
CREB-regulated transcription coactivator 3
Required for interaction with HTLV-1 TAX
Required for interaction with PPP2CA and PPP2R1A
Transducer of regulated CREB activity C-terminal
Transducer of regulated CREB activity middle
Translocates to the cytoplasm. Represses basal TORC3 activity towards CREB.
More susceptible to N-terminal truncation and shows greater distribution to the VLDL than the protein with T-71.
Tubulin polyglutamylase complex subunit 1
In MPOD; affects proteolytic processing and secretion.
In MPOD; suppress post-translational processing.
In MISSLA; loss of nuclear localization.
In MISSLA; reduced nuclear localization.
In MISSLA; reduced protein level; reduced nuclear localization.
In MISSLA; unknown pathological significance.
In MISSLA; unknown pathological significance; reduced protein level; no effect on nuclear localization; does not complement loss of endogenous DONSON when tested for the rescue of the spontaneous fork stalling observed after DONSON depletion.
No effect on nuclear localization; complements loss of endogenous DONSON by rescuing the spontaneous fork stalling observed after DONSON depletion.
Decreased sterol transport; probable decreased expression due to nonsense-mediated decay.
Steroid transmembrane transporter SLC22A24
In PARK; sporadic case; unknown pathological significance.
In PARK; unknown pathological significance.
In PARK; unknown pathological significance; affects regulation of endosomal membrane trafficking as indicated by accumulation of transferrin in endosomal compartments.
Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-39.
Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-48.
Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-37 or E-37.
Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-46 or E-46.
Eukaryotic translation initiation factor 4E-binding protein 2
In MC4DN12; results in impaired complex IV assembly.
Polypeptide N-acetylgalactosaminyltransferase-like 6
Eukaryotic glycogen debranching enzyme N-terminal
Glycogen debranching enzyme glucanotransferase
In GSD3; deficient in ability to bind glycogen; unstable due to enhanced ubiquitination; forms aggresomes upon proteasome impairment.
In CMT1J; decreased inositol trisphosphate-mediated calcium release and altered calcium homeostasis in patient fibroblasts.
In CMT1J; unknown pathological significance.
Inositol 1,4,5-trisphosphate receptor type 3
Epithelial-stromal interaction protein 1
Submaxillary gland androgen-regulated protein 3A
Loss of FOXO1 methylation, its nuclear retention, and transcriptional activity.
No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-280 and A-322. No effect on homodimerization but loss of homooligomerization; when associated with A-280 and A-322.
No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-280 and A-359. No effect on homodimerization but loss of homooligomerization; when associated with A-280 and A-359.
No effect on S-adenosyl-L-methionine binding but reduced EWS protein methylation; when associated with A-322 and A-359. No effect on homodimerization but loss of homooligomerization; when associated with A-322 and A-359.
Neuronal acetylcholine receptor subunit beta-3
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
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.
Coiled-coil domain-containing protein 120
Common allele; associated with susceptibility to IBD13; has decreased enzyme activity.
In a colchicine-selected multidrug-resistant cell line; confers increased resistance to colchicine.
Opioid growth factor receptor-like protein 1
Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-741.
Abolishes down-regulation of kinase activity by PKC/PRKCA-mediated phosphorylation; when associated with A-746.
Important for interaction with phosphotyrosine-binding proteins
In MASTC; somatic mutation; constitutively activated; requires 2 nucleotide substitutions.
In MASTC; sporadic case; somatic mutation; dominant negative mutation; loss of autophosphorylation.
In MASTC; sporadic case; somatic mutation; requires 2 nucleotide substitutions; constitutively activated and is much more rapidly autophosphorylated than wild type.
In MASTC; unknown pathological significance.
In MASTSYS and MASTC; also found in acute myeloid leukemia and a germ cell tumor of the testis; somatic mutation; constitutively activated.
In MASTSYS, MASTC and mast cell leukemia; somatic mutation; constitutively activated; loss of interaction with MPDZ.
In a germ cell tumor of the testis; somatic mutation.
In a testicular tumor; seminoma; somatic mutation; constitutively activated.
Mast/stem cell growth factor receptor Kit
No decrease in activity. Leads to autophosphorylation at Tyr-900.
Reduces autophosphorylation in response to KITLG/SCF.
Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-571.
Reduction in SH2B2/APS binding. Abolishes SH2B2/APS binding; when associated with A-939.
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.
Abolishes secretion and modulation of exocytosis.
Abolishes secretion and nearly abolishes modulation of exocytosis.
No effect on secretion and modulation of exocytosis.
Translation initiation factor IF-2, mitochondrial
Cation-independent mannose-6-phosphate receptor
Large ribosomal subunit protein uL5 C-terminal
Large ribosomal subunit protein uL5 N-terminal
Probable cation-transporting ATPase 13A4
In APRS; requires 2 nucleotide substitutions.
In BBDS1; the mutation selectively reduces plasma-membrane levels of the protein and markedly diminishes the receptor's responsiveness to extracellular FGF.
In CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface.
In LADD1; strongly reduced kinase activity.
In PS; requires 2 nucleotide substitutions.
In PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation.
In a non-syndromic craniosynostosis patient with abnormal intrauterine history; confers predisposition to craniosynostosis.
In craniosynostosis; constitutive kinase activity.
In isoform 2, isoform 7, isoform 11 and isoform 16.
In isoform 3, isoform 4, isoform 11, isoform 12, isoform 13 and isoform 16.
In isoform 4, isoform 15 and isoform 16.
In isoform 4, isoform 5, isoform 6, isoform 7, isoform 10 and isoform 12.
Increases fibroblast proliferation. Decreases phosphorylation of PLCG1 and FRS2. Decreases activation of MAP kinases.
Reduced N-glycosylation. Reduced expression at the cell surface.
Necessary for interaction with CREB1 and NRF1
Necessary for interaction with CREB1 and NRF1 and for transcriptional coactivation
Peroxisome proliferator-activated receptor gamma coactivator-related protein 1
Translation initiation factor IF-3, mitochondrial
No effect on interaction with HSPA8 and HSP90AB1. Loss of interaction with CDC6.
No effect on interaction with HSPA8, HSP90AB1 and CDC6.
Decreases androsterone dehydrogenase activity; when associated with F-176.
Decreases androsterone dehydrogenase activity; when associated with R-180.
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
In EPM3; results in markedly diminished localization at the cell membrane and appearance of prominent cytoplasmic aggregates.
In EPM3; uncertain pathological significance.
Probable disease-associated variant found in a patient with opsoclonus-myoclonus ataxia-like syndrome.
Adenylyltransferase and sulfurtransferase MOCS3
Cysteine persulfide intermediate; for sulfurtransferase activity
Does not affect sulfurtransferase activity.
Does not affect sulfurtransferase specificity and activity.
Glycyl thioester intermediate; for adenylyltransferase activity
Deoxynucleotidyltransferase terminal-interacting protein 1
Important for DNA and nucleosome binding
Found in a patient with autism spectrum disorder and no epileptic seizures; unknown pathological significance.
Gamma-aminobutyric acid receptor subunit alpha-3
In EPILX2; unknown pathological significance.
Spindle and kinetochore-associated protein 3
Phosphoenolpyruvate carboxykinase C-terminal P-loop
Phosphoenolpyruvate carboxykinase GTP-utilising N-terminal
Phosphoenolpyruvate carboxykinase [GTP], mitochondrial
Transcription factor IIIB 90 kDa subunit
Ankyrin repeat and MYND domain-containing protein 2
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
(Microbial infection) Cleavage; by N.americanus apr-2
In Adana; unstable; causes alpha-thalassemia.
In Bassett; markedly reduced oxygen affinity.
In Bibba; unstable; causes alpha-thalassemia.
In Clinic; unstable; causes alpha-thalassemia.
In Kokura; also in Umi/Michigan; unstable.
In M-Boston/M-Osaka; O(2) affinity down.
In Petah Tikva; unstable; causes alpha-thalassemia.
In Plasencia; family with moderate microcytosis and hypochromia.
In Questembert; highly unstable; causes alpha-thalassemia.
In Ravenscourt Park; causes alpha-thalassemia.
In Suan-Dok; unstable; causes alpha-thalassemia.
In Tunis-Bizerte; unstable; causes alpha-thalassemia.
N-linked (Glc) (glycation) lysine; alternate
Probable ATP-dependent RNA helicase DDX52
Breakpoint for insertion to form FCRL4-IGHA1 fusion protein
Loss of function, phosphorylation and interaction with PTPN6 and PTPN11.
Loss of interaction with PTPN6 and PTPN11 and partial loss of function and phosphorylation.
No effect on function, phosphorylation and interaction with PTPN6 and PTPN11.
Mediates interaction with ANKS1A and ANKS1B
Mediates interaction with PIK3CG and required for endocytosis
Mediates interaction with hepatitis C virus non-structural protein NS5A
Completely blocks cleavage by caspase-3, -6, and -8 and dramatic suppression of EBVDNA replication; when associated with A-100.
Completely blocks cleavage by caspase-3, -6, and -8 and dramatic suppression of EBVDNA replication; when associated with A-433.
Loss of UBE2I-binding; almost complete loss of promotion of TP53 sumoylation; no loss of SUMO1- and TP53-binding.
No effect on cleavages by caspase-6 and -8.
Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-135.
Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-42 and R-43.
Abrogates ASB2alpha-mediated degradation without altering ASB2alpha binding; when associated with R-43 and R-135.
In FMD1; does not inhibit interaction with MIS18BP1.
In FMD1; unknown pathological significance.
In MNS; does not inhibit interaction with MIS18BP1.
In MNS; unknown pathological significance.
In OPD1; unknown pathological significance.
In OPD2; unknown pathological significance.
Probable disease-associated variant found in a patient with macrothrombocytopenia.
Vacuolar protein sorting-associated protein 26C
Coiled-coil domain-containing protein 154
Found in a patient with left-sided obstructive cardiac lesions; unknown pathological significance.
Found in a patient with left-sided obstructive cardiac lesions; unknown pathological significance; alters Ca(2+)-binding affinity.
Multiple C2 and transmembrane domain-containing protein 2
Associated with susceptibility to infection with Mycobacterium ulcerans.
Natural resistance-associated macrophage protein 1