CYP3A4

Homo sapiens (Human)

Taurochenodeoxycholate 6-alpha-hydroxylase; Quinine 3-monooxygenase; P450-PCN1; Nifedipine oxidase; NF-25; HLp; Cytochrome P450-PCN1; Cytochrome P450 NF-25; Cytochrome P450 HLp; Cytochrome P450 3A4; C

Cytochrome P450 family

Paired donor oxygen oxidoreductase

In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e. g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide. Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole. Cytochromes P450 are a group of heme-thiolate monooxygenases.

Vitamin D-dependent rickets 3 (VDDR3) [MIM:619073]: An autosomal dominant disorder of vitamin D metabolism resulting in early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. {ECO:0000269|PubMed:29461981}. The gene represented in this entry is involved in disease pathogenesis.

DB08496; DB14055; DB12537; DB12629; DB01456; DB04070; DB11919; DB12515; DB11932; DB12001; DB05812; DB14973; DB11703; DB01418; DB00316; DB00819; DB15568; DB00546; DB08838; DB00518; DB00240; DB00041; DB04630; DB00802; DB00346; DB09026; DB00918; DB06203; DB00969; DB12015; DB14003; DB00404; DB06403; DB06742; DB13141; DB00288; DB00357; DB01424; DB01223; DB01118; DB00321; DB00381; DB00701; DB01217; DB01536; DB01435; DB11901; DB06605; DB00714; DB05676; DB00673; DB01352; DB09229; DB00278; DB01238; DB14185; DB06413; DB01169; DB06697; DB12597; DB06216; DB00637; DB11586; DB01072; DB16098; DB01076; DB01117; DB15011; DB06237; DB15233; DB06442; DB11995; DB06318; DB06626; DB00972; DB09230; DB04957; DB00207; DB12781; DB13997; DB04975; DB01483; DB11817; DB09227; DB00394; DB08903; DB05015; DB16703; DB15463; DB13488; DB09231; DB00865; DB01244; DB15982; DB00443; DB14669; DB12236; DB00307; DB01393; DB01128; DB11799; DB04794; DB00905; DB13746; DB16536; DB00612; DB13975; DB09223; DB08873; DB00188; DB00559; DB06616; DB07348; DB08870; DB09128; DB12267; DB01194; DB05541; DB01200; DB09017; DB11752; DB01222; DB00297; DB00921; DB00490; DB01008; DB09173; DB06772; DB00248; DB08875; DB00201; DB04886; DB00136; DB08907; DB01152; DB09061; DB14737; DB12218; DB11791; DB08502; DB06774; DB00564; DB11383; DB11960; DB06016; DB13835; DB01136; DB14984; DB06634; DB00520; DB01333; DB00482; DB06119; DB09063; DB00439; DB06419; DB00185; DB06777; DB00446; DB00475; DB13528; DB00608; DB00856; DB01114; DB00477; DB00356; DB00169; DB01410; DB09201; DB09232; DB01166; DB00501; DB01012; DB00568; DB00537; DB00604; DB00215; DB01211; DB12499; DB04920; DB01190; DB00349; DB11750; DB01013; DB13158; DB14652; DB00845; DB00636; DB06470; DB01242; DB01068; DB00575; DB00758; DB13843; DB00628; DB01559; DB00257; DB00363; DB09065; DB05239; DB00907; DB00318; DB01394; DB06342; DB00872; DB00286; DB12483; DB04652; DB01285; DB14681; DB01380; DB13003; DB08865; DB11672; DB14635; DB04838; DB00924; DB00531; DB00091; DB04839; DB00987; DB08912; DB09102; DB11963; DB01764; DB01406; DB11779; DB06292; DB04884; DB11682; DB00250; DB15031; DB00496; DB09234; DB12941; DB01264; DB09183; DB01254; DB00694; DB01609; DB11921; DB11943; DB11637; DB00705; DB13857; DB01151; DB00304; DB01260; DB06780; DB01134; DB06700; DB12161; DB01234; DB14649; DB11487; DB09555; DB05351; DB04856; DB14068; DB00514; DB00647; DB14063; DB11994; DB00829; DB00586; DB00485; DB09123; DB00255; DB09095; DB06781; DB01396; DB11274; DB01551; DB11273; DB13345; DB13385; DB00320; DB00343; DB01093; DB08995; DB13347; DB00954; DB00280; DB00822; DB02520; DB01248; DB00204; DB00757; DB08930; DB01184; DB00843; DB11400; DB12301; DB06446; DB05928; DB00590; DB01142; DB00997; DB00254; DB00470; DB04855; DB01395; DB00476; DB11952; DB00378; DB11742; DB14240; DB01127; DB14598; DB14600; DB00625; DB09235; DB06374; DB11979; DB11574; DB00216; DB15444; DB09039; DB09101; DB14064; DB13874; DB11718; DB13007; DB11986; DB08899; DB08992; DB00751; DB00668; DB00700; DB12266; DB01873; DB11405; DB03515; DB02187; DB12329; DB12147; DB01049; DB01253; DB00696; DB00530; DB00199; DB01175; DB11823; DB14575; DB09119; DB00736; DB01215; DB09381; DB12235; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB01196; DB00655; DB04574; DB00402; DB00330; DB00898; DB00977; DB00593; DB08794; DB01466; DB00823; DB09166; DB00294; DB00773; DB01628; DB14766; DB06414; DB13866; DB01590; DB00990; DB00973; DB12500; DB00949; DB01023; DB08980; DB00574; DB00813; DB06702; DB12265; DB08874; DB01216; DB16165; DB13961; DB04908; DB00301; DB00196; DB00687; DB00663; DB04841; DB00180; DB01544; DB00591; DB01047; DB08971; DB00324; DB00472; DB08970; DB14634; DB09378; DB14637; DB00846; DB00690; DB13338; DB04842; DB00499; DB13867; DB08906; DB00588; DB01095; DB00176; DB12307; DB08905; DB01319; DB06717; DB14019; DB01320; DB12010; DB11796; DB11679; DB00947; DB02703; DB15149; DB00674; DB12923; DB05087; DB00317; DB01241; DB01645; DB12184; DB06730; DB11619; DB12141; DB01381; DB11978; DB13879; DB00143; DB01016; DB08909; DB00986; DB05814; DB00889; DB10534; DB11575; DB00365; DB00400; DB01018; DB06786; DB01218; DB13728; DB00502; DB01159; DB05212; DB01275; DB00956; DB00769; DB00741; DB14538; DB14539; DB14540; DB14541; DB14542; DB14543; DB14545; DB14544; DB01611; DB14570; DB06789; DB00557; DB12471; DB09053; DB01050; DB11737; DB09054; DB01181; DB04946; DB00619; DB09262; DB00458; DB00724; DB05039; DB08953; DB00808; DB00224; DB06370; DB11886; DB13293; DB01029; DB00762; DB11633; DB06636; DB00951; DB00982; DB00270; DB11757; DB01167; DB09083; DB08820; DB00602; DB14568; DB04845; DB09570; DB01221; DB01587; DB06738; DB01026; DB09309; DB05903; DB09236; DB06218; DB06791; DB00448; DB01259; DB06685; DB14723; DB12825; DB11951; DB15673; DB16217; DB09078; DB00528; DB11560; DB06469; DB12070; DB01006; DB01227; DB09237; DB01002; DB06282; DB05667; DB00825; DB08918; DB00367; DB00281; DB13766; DB08882; DB17083; DB01583; DB00589; DB09198; DB14065; DB08827; DB01206; DB06448; DB16222; DB00836; DB01601; DB00455; DB00186; DB04871; DB12130; DB09195; DB12089; DB00678; DB14596; DB00227; DB09212; DB08933; DB09280; DB06077; DB06708; DB08815; DB12674; DB12474; DB04829; DB13074; DB08932; DB09238; DB16226; DB04835; DB06234; DB14921; DB00643; DB14009; DB09124; DB00603; DB00253; DB00358; DB00351; DB11529; DB14659; DB00814; DB00170; DB00454; DB09383; DB01071; DB01357; DB04817; DB00333; DB04833; DB00763; DB00563; DB01028; DB09241; DB00353; DB00959; DB14644; DB12952; DB06710; DB00247; DB01233; DB00264; DB00916; DB01011; DB15489; DB00379; DB06148; DB01388; DB01110; DB00683; DB13456; DB06595; DB00834; DB04896; DB13287; DB08893; DB11792; DB00370; DB12489; DB16236; DB06587; DB00648; DB01204; DB16390; DB00745; DB11763; DB00764; DB14512; DB00471; DB00295; DB09205; DB00688; DB01024; DB11605; DB00486; DB14011; DB00607; DB12092; DB11691; DB06230; DB09049; DB01183; DB00731; DB04861; DB01149; DB00220; DB11828; DB09199; DB09048; DB00238; DB00627; DB00622; DB02701; DB00184; DB01115; DB09239; DB04868; DB09240; DB06712; DB04743; DB00393; DB09079; DB16691; DB12005; DB00401; DB01595; DB01054; DB00435; DB11636; DB13981; DB06713; DB14678; DB00717; DB09371; DB01059; DB00957; DB09389; DB00540; DB06174; DB06152; DB00104; DB06670; DB00334; DB09074; DB11442; DB14881; DB00768; DB16267; DB12513; DB09568; DB00338; DB00904; DB11130; DB04911; DB01083; DB01173; DB11837; DB09330; DB04938; DB13500; DB00776; DB12532; DB00239; DB01062; DB00497; DB06412; DB01192; DB12612; DB01229; DB11697; DB09073; DB01267; DB00377; DB05467; DB06603; DB00213; DB00617; DB01384; DB08439; DB00910; DB09297; DB00715; DB06663; DB03010; DB06589; DB00082; DB15102; DB13791; DB00312; DB11198; DB08883; DB01186; DB01074; DB08922; DB00850; DB12978; DB03783; DB00780; DB01174; DB00946; DB00191; DB00812; DB00252; DB13878; DB01085; DB05316; DB00337; DB01100; DB06762; DB09090; DB01132; DB13941; DB12582; DB01621; DB04951; DB17472; DB11642; DB04977; DB12240; DB08910; DB08901; DB12016; DB01263; DB05478; DB15822; DB01411; DB06209; DB01588; DB01058; DB01130; DB00860; DB15566; DB14633; DB14631; DB00635; DB14646; DB13208; DB02789; DB04825; DB05154; DB01087; DB00794; DB01032; DB00396; DB00420; DB13602; DB09288; DB01182; DB12278; DB00571; DB06480; DB00545; DB01589; DB04216; DB01224; DB01103; DB13685; DB00908; DB00468; DB01369; DB12874; DB01129; DB00481; DB00980; DB00863; DB00243; DB00234; DB08896; DB11853; DB06458; DB14761; DB00409; DB00912; DB16826; DB02709; DB01256; DB13174; DB11730; DB06233; DB00615; DB04934; DB01045; DB11753; DB01201; DB01220; DB08864; DB12457; DB00896; DB06155; DB08931; DB14840; DB15305; DB00734; DB14924; DB00503; DB06228; DB09200; DB00533; DB01656; DB13409; DB09291; DB06176; DB00296; DB00412; DB05271; DB00778; DB12332; DB06201; DB11614; DB01698; DB08877; DB06654; DB12391; DB01001; DB00938; DB12543; DB01232; DB11805; DB11767; DB06335; DB00747; DB12834; DB14583; DB11459; DB01037; DB05885; DB11362; DB11942; DB15685; DB11689; DB06731; DB06739; DB06144; DB01104; DB01236; DB01105; DB00203; DB06207; DB09036; DB06290; DB00641; DB12371; DB00877; DB01261; DB06268; DB05482; DB01591; DB09308; DB09099; DB09143; DB00398; DB12713; DB15569; DB12548; DB01323; DB09118; DB00708; DB00359; DB01015; DB01138; DB01268; DB09034; DB09317; DB09318; DB00864; DB00820; DB00675; DB00706; DB06083; DB09071; DB01349; DB08833; DB12887; DB12020; DB05521; DB00976; DB12095; DB00231; DB06287; DB11761; DB00444; DB09299; DB15133; DB00857; DB00342; DB13399; DB13725; DB04905; DB00624; DB13943; DB13944; DB01420; DB13946; DB00759; DB12093; DB14066; DB11712; DB01041; DB00277; DB01154; DB00599; DB04572; DB00906; DB09289; DB08816; DB11470; DB00911; DB01007; DB01409; DB00932; DB06137; DB16732; DB11800; DB06273; DB11635; DB11251; DB08895; DB08811; DB09216; DB01036; DB06212; DB00273; DB01685; DB00539; DB05109; DB00193; DB08911; DB07615; DB00752; DB14962; DB05773; DB00656; DB00755; DB00620; DB00897; DB12245; DB12808; DB09089; DB00347; DB00440; DB06045; DB00197; DB13179; DB11652; DB15328; DB06267; DB08867; DB14989; DB13609; DB15091; DB01586; DB12255; DB11915; DB00580; DB00313; DB15114; DB05294; DB03701; DB04894; DB00862; DB11613; DB08881; DB11581; DB00285; DB00661; DB14895; DB06652; DB09082; DB06684; DB09185; DB00570; DB00541; DB00309; DB11641; DB00361; DB12131; DB08828; DB11094; DB00163; DB11693; DB11739; DB09030; DB00582; DB09068; DB14975; DB12026; DB00682; DB13950; DB01392; DB00549; DB00962; DB15035; DB15688; DB00495; DB00744; DB04832; DB00246; DB00425; DB04828; DB00909; DB01198; DB09225; DB01624; DB15490

O15287; Q6ZQX7-4

EC 1.14.14.-

3D-structure; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation

A

52195.6

456

0.11

44.02

8.48

4.36

-6.26

USP1

Homo sapiens (Human)

hUBP; Ubiquitin-specific-processing protease 1; Ubiquitin thioesterase 1; Ubiquitin carboxyl-terminal hydrolase 1

Peptidase C19 family

Peptidase

Involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2.

Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}. The gene represented in this entry is involved in disease pathogenesis. Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences. {ECO:0000269|PubMed:19327734, ECO:0000269|PubMed:21357617}.; DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1 (SSFSC1) [MIM:617877]: An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract. {ECO:0000269|PubMed:29198724}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q8TAF3; Q8TAF3-1

EC 3.4.19.12

3D-structure; Autocatalytic cleavage; DNA damage; DNA repair; Hydrolase; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation; Ubl conjugation pathway

D

32426

285

0.1

50.73

5.85

-4.67

-6.25

GLB1

Homo sapiens (Human)

Lactase; Elastin receptor 1; ELNR1; Acid beta-galactosidase

Glycosyl hydrolase 35 family

NA

Isoform 1: Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.

GM1-gangliosidosis 1 (GM1G1) [MIM:230500]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life. {ECO:0000269|PubMed:10338095, ECO:0000269|PubMed:10737981, ECO:0000269|PubMed:10839995, ECO:0000269|PubMed:1487238, ECO:0000269|PubMed:15365997, ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:15791924, ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:1928092, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8213816, ECO:0000269|Ref.28, ECO:0000269|Ref.31}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: GM1-gangliosidosis 2 (GM1G2) [MIM:230600]: A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive. {ECO:0000269|PubMed:10737981, ECO:0000269|PubMed:12644936, ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8213816}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: GM1-gangliosidosis 3 (GM1G3) [MIM:230650]: A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive. {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:15986423, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8198123, ECO:0000269|Ref.28, ECO:0000269|Ref.30}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mucopolysaccharidosis 4B (MPS4B) [MIM:253010]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:12393180, ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1928092, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:7586649}. The disease is caused by variants affecting the gene represented in this entry.

DB04465

Q8NBJ4; Q3KNW5; Q9BRI3; P30825

EC 3.2.1.23

3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; Gangliosidosis; Glycoprotein; Glycosidase; Hydrolase; Lysosome; Mucopolysaccharidosis; Proteomics identification; Reference proteome; Signal; Zymogen

A

67980.6

605

0.13

40.91

5.81

-9.05

-6.26

CDK4

Homo sapiens (Human)

NA

NA

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily

Cell cycle

ATP binding.Cyclin binding.Cyclin-dependent protein serine/threonine kinase activity.Cyclin-dependent protein serine/threonine kinase regulator activity.Protein complex binding.

Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. {ECO:0000269|PubMed:7652577, ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, ECO:0000269|PubMed:9425228}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB12001; DB03496; DB12010; DB09073; DB02733; DB11730; DB15442

Q9UH17; P24385; P30279; P30281; Q16543; P50613; P38936; P46527; P49918; P42771; P42772; P42773; P55273; Q9UJC3; P08238; Q9UKT9; Q0VD86; P01106; Q9ULD0; P28749; Q08999; P09936; Q8N720

2.7.11.22

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; Cytoplasm; Disease variant; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

B

30138.4

267

0.09

36.2

5.78

-5.83

-6.24

OTC

Homo sapiens (Human)

OTCase; Ornithine carbamoyltransferase, mitochondrial

Aspartate/ornithine carbamoyltransferase superfamily, OTCase family

NA

Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline. The urea cycle ensures the detoxification of ammonia by converting it to urea for excretion.

Ornithine carbamoyltransferase deficiency (OTCD) [MIM:311250]: An X-linked disorder of the urea cycle which causes a form of hyperammonemia. Mutations with no residual enzyme activity are always expressed in hemizygote males by a very severe neonatal hyperammonemic coma that generally proves to be fatal. Heterozygous females are either asymptomatic or express orotic aciduria spontaneously or after protein intake. The disorder is treatable with supplemental dietary arginine and low protein diet. The arbitrary classification of patients into the 'neonatal' group (clinical hyperammonemia in the first few days of life) and 'late' onset (clinical presentation after the neonatal period) has been used to differentiate severe from mild forms. {ECO:0000269|PubMed:10070627, ECO:0000269|PubMed:10502831, ECO:0000269|PubMed:10737985, ECO:0000269|PubMed:11793483, ECO:0000269|PubMed:1480464, ECO:0000269|PubMed:1671317, ECO:0000269|PubMed:1721894, ECO:0000269|PubMed:2347583, ECO:0000269|PubMed:2474822, ECO:0000269|PubMed:2556444, ECO:0000269|PubMed:3170748, ECO:0000269|PubMed:7474905, ECO:0000269|PubMed:7951259, ECO:0000269|PubMed:8019569, ECO:0000269|PubMed:8081373, ECO:0000269|PubMed:8081398, ECO:0000269|PubMed:8099056, ECO:0000269|PubMed:8112735, ECO:0000269|PubMed:8530002, ECO:0000269|PubMed:8807340, ECO:0000269|PubMed:8830175, ECO:0000269|PubMed:8956038, ECO:0000269|PubMed:8956045, ECO:0000269|PubMed:9065786, ECO:0000269|PubMed:9143919, ECO:0000269|PubMed:9266388, ECO:0000269|PubMed:9286441, ECO:0000269|PubMed:9452024, ECO:0000269|PubMed:9452049, ECO:0000269|PubMed:9452065, ECO:0000269|Ref.32, ECO:0000269|Ref.43}. The disease is caused by variants affecting the gene represented in this entry.

DB00155; DB02011; DB04185; DB00129

NA

EC 2.1.3.3

3D-structure; Acetylation; Amino-acid biosynthesis; Arginine biosynthesis; Disease variant; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Transit peptide; Urea cycle

A

36060.2

321

0.08

36.44

7.87

1.48

-6.24

ALS

Arabidopsis thaliana (Mouse-ear cress)

NA

At3g48560;CSR1;AHAS;T8P19.70;TZP5

TPP enzyme family

NA

Catalyzes the formation of acetolactate from pyruvate, the first step in valine and isoleucine biosynthesis. {ECO:0000269|PubMed:10386618, ECO:0000269|PubMed:16665813, ECO:0000269|PubMed:16667374, ECO:0000269|PubMed:16668488, ECO:0000269|PubMed:2336405, ECO:0000269|PubMed:8913312, ECO:0000269|PubMed:9355748, ECO:0000269|PubMed:9677339, ECO:0000269|Ref.9}."

Niemann-Pick disease A (NPDA) [MIM:257200]: An early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, intellectual disability, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. {ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1391960, ECO:0000269|PubMed:15221801, ECO:0000269|PubMed:15877209, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:1718266, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:2023926, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430884, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:8680412, ECO:0000269|PubMed:8693491, ECO:0000269|PubMed:9266408, ECO:0000269|PubMed:9660788}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood. {ECO:0000269|PubMed:12369017, ECO:0000269|PubMed:12556236, ECO:0000269|PubMed:1301192, ECO:0000269|PubMed:15241805, ECO:0000269|PubMed:16010684, ECO:0000269|PubMed:1618760, ECO:0000269|PubMed:16472269, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:1885770, ECO:0000269|PubMed:19050888, ECO:0000269|PubMed:19405096, ECO:0000269|PubMed:20386867, ECO:0000269|PubMed:21098024, ECO:0000269|PubMed:21621718, ECO:0000269|PubMed:22613662, ECO:0000269|PubMed:22818240, ECO:0000269|PubMed:23252888, ECO:0000269|PubMed:23430512, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:26084044, ECO:0000269|PubMed:26499107, ECO:0000269|PubMed:27338287, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8051942, ECO:0000269|PubMed:8664904}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

2.2.1.6

3D-structure; Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Chloroplast; Coiled coil; FAD; Flavoprotein; Genetically modified food; Herbicide resistance; Magnesium; Metal-binding; Oxidation; Plastid; Reference proteome; Thiamine pyrophosphate; Transferase; Transit peptide

A

63431

583

0.07

36.62

5.4

-15.33

-6.24

bglA

Paenibacillus polymyxa (Bacillus polymyxa)

NA

NA

Glycosyl hydrolase 1 family

Hydrolase

Beta-glucosidase activity.Scopolin beta-glucosidase activity.

Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:15645182}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

DB02658; DB04282; DB04304

NA

3.2.1.21

3D-structure; Carbohydrate metabolism; Cellulose degradation; Glycosidase; Hydrolase; Polysaccharide degradation

A

51515.2

447

0.14

38.44

5.28

-18.1

-6.25

NT5E

Homo sapiens (Human)

NT5; CD73 antigen; 5'-nucleotidase; 5'-NT

5'-nucleotidase family

Phosphoric monoester hydrolase

Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Hydrolyzes extracellular nucleotides into membrane permeable nucleosides.

Calcification of joints and arteries (CALJA) [MIM:211800]: A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. {ECO:0000269|PubMed:21288095, ECO:0000269|PubMed:24887587}. The disease is caused by variants affecting the gene represented in this entry.

DB00987; DB00806

Q9Y225-2; Q8WWF5

EC 3.1.3.5

3D-structure; Alternative splicing; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane; Metal-binding; Nucleotide-binding; Proteomics identification; Reference proteome; Signal; Zinc

A

24417.6

219

0.09

40.43

5.49

-5.75

-6.25

ACP1

Homo sapiens (Human)

NA

NA

Low molecular weight phosphotyrosine protein phosphatase family

hydrolase / hydrolase inhibitor

Acid phosphatase activity.Non-membrane spanning protein tyrosine phosphatase activity.

Waardenburg syndrome 4A (WS4A) [MIM:277580]: A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). {ECO:0000269|PubMed:12189494, ECO:0000269|PubMed:8634719}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hirschsprung disease 2 (HSCR2) [MIM:600155]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269|PubMed:11471546, ECO:0000269|PubMed:28236341, ECO:0000269|PubMed:8001158, ECO:0000269|PubMed:8630503, ECO:0000269|PubMed:8852660}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: ABCD syndrome (ABCDS) [MIM:600501]: An autosomal recessive syndrome characterized by albinism, black lock at temporal occipital region, bilateral deafness, aganglionosis of the large intestine and total absence of neurocytes and nerve fibers in the small intestine. {ECO:0000269|PubMed:11891690}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Heterozygous mutations in EDNRB may be responsible for Waardenburg syndrome 2, an autosomal dominant disorder characterized by sensorineural deafness and pigmentary disturbances. {ECO:0000269|PubMed:28236341}.

DB04214; DB00173

Q96CV9

3.1.3.2; 3.1.3.48

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Hydrolase; Phosphoprotein; Protein phosphatase; Proteomics identification; Reference proteome

A

17582.8

154

0.09

50.52

7

-0

-6.24

MAT2A

Homo sapiens (Human)

Methionine adenosyltransferase II; Methionine adenosyltransferase 2; MAT-II; MAT 2; AdoMet synthase 2

AdoMet synthase family

AdoMet synthase family

Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB00118; DB00134

Q96IK1-2; Q96NX5; Q6ZP82-1; Q8IUI8; Q6P1L5; P15976-2; P80217-2; Q8WZ19; Q9UIH9; Q00266; P31153; Q9NZL9; P02795; Q9BRX2; O43663; O43741; P57052; Q8N488; P08195-4; Q13573; Q86W54-2; O95789-4

EC 2.5.1.6

3D-structure; Acetylation; Alternative splicing; ATP-binding; Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; One-carbon metabolism; Phosphoprotein; Potassium; Proteomics identification; Reference proteome; Transferase; Ubl conjugation

A

42071.4

381

0.08

38.24

6.21

-4.13

-6.24

PFF0160c

Plasmodium falciparum (isolate 3D7)

NA

NA

Dihydroorotate dehydrogenase family, Type 2 subfamily

Oxidoreductase

Dihydroorotate dehydrogenase activity.

Combined oxidative phosphorylation deficiency 33 (COXPD33) [MIM:617713]: An autosomal recessive disorder caused by multiple mitochondrial respiratory chain defects and impaired mitochondrial energy metabolism. Clinical manifestations are highly variable. Affected infants present with cardiomyopathy accompanied by multisystemic features involving liver, kidney, and brain. Death in infancy is observed in some patients. Children and adults present with myopathy and progressive external ophthalmoplegia. {ECO:0000269|PubMed:28942965}. The disease is caused by variants affecting the gene represented in this entry.

DB01117

NA

1.3.5.2

3D-structure; Flavoprotein; FMN; Membrane; Mitochondrion; Mitochondrion inner membrane; Oxidoreductase; Pyrimidine biosynthesis; Reference proteome; Transit peptide; Transmembrane; Transmembrane helix

A,B

42573.5

378

0.1

36.63

8.21

3.17

-6.25

ACACA

Homo sapiens (Human)

NA

ACAC;ACCA;ACC1

NA

Ligase

Acetyl-CoA carboxylase activity.ATP binding.Biotin carboxylase activity.Identical protein binding.Metal ion binding.

Acetyl-CoA carboxylase-alpha deficiency (ACACAD) [MIM:613933]: An autosomal recessive inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. {ECO:0000269|PubMed:6114432}. The disease is caused by variants affecting the gene represented in this entry.

DB00121

Q13085; O60218; P38398; Q96EB6; Q9CQ20; P02654; Q92915-2; Q6NTF9-3

6.4.1.2

3D-structure; Acetylation; Allosteric enzyme; Alternative promoter usage; ATP-binding; Biotin; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis; Lipid metabolism; Magnesium; Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome

A,B

54237.7

486

0.09

39.18

6.37

-2.46

-6.25

PTK6

Homo sapiens (Human)

Protein-tyrosine kinase 6; Breast tumor kinase; BRK

Protein kinase superfamily, Tyr protein kinase family, BRK/PTK6/SIK subfamily

Kinase

Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.

Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269|PubMed:17418573, ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:7987325, ECO:0000269|PubMed:8004673}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. {ECO:0000269|PubMed:9199552}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. {ECO:0000269|PubMed:15001631}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 18 (CMYO18) [MIM:620246]: A congenital myopathy of variable severity, ranging from severe fetal akinesia to milder forms of muscle weakness. Most affected individuals show delayed motor development with generalized hypotonia and progressive axial and limb muscle weakness beginning soon after birth or in infancy. Additional features may include swallowing difficulties, external ophthalmoplegia, ptosis, high-arched palate, and respiratory insufficiency. Muscle biopsy shows variable morphologic abnormalities, including alveolar changes in the intermyofibrillar network, fiber size variability, focal disorganization, internal nuclei, and dilated sarcoplasmic reticulum and T-tubules. CMYO18 inheritance is autosomal dominant or recessive. {ECO:0000269|PubMed:28012042, ECO:0000269|PubMed:31227654, ECO:0000269|PubMed:33060286}. The disease is caused by variants affecting the gene represented in this entry.

DB12010; DB11800; DB05294; DB15035

Q08043; Q3KP44; Q13191; Q16543; Q92841; Q8N9I9; Q5JST6; P04626; O00471; O14526; Q13480; P08238; P42858; Q9UKT9; Q5VWX1; Q5T5P2-6; P10721; O14770-4; Q13064; Q8TDC0; P78337; Q9NQX0; Q13882; Q04864; P23246; Q13239-3; O00401; Q9BYN7

EC 2.7.10.2

3D-structure; Alternative splicing; ATP-binding; Cell projection; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase

A

30240.6

264

0.09

46.88

6.95

-0.14

-6.24

GRM3

Homo sapiens (Human)

mGLUR3; Group III metabotropic glutamate receptor; GPRC1C

G-protein coupled receptor 3 family

GPCR glutamate

Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity. G-protein coupled receptor for glutamate.

Paramyotonia congenita (PMC) [MIM:168300]: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP. {ECO:0000269|PubMed:10369308, ECO:0000269|PubMed:10727489, ECO:0000269|PubMed:1310898, ECO:0000269|PubMed:1316765, ECO:0000269|PubMed:1338909, ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:15790667, ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19077043, ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:8242056, ECO:0000269|PubMed:8308722, ECO:0000269|PubMed:8388676, ECO:0000269|PubMed:8580427}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269|PubMed:10599760, ECO:0000269|PubMed:10851391, ECO:0000269|PubMed:10944223, ECO:0000269|PubMed:11558801, ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:20522878, ECO:0000269|PubMed:21043388, ECO:0000269|PubMed:24549961}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients. {ECO:0000269|PubMed:1659668, ECO:0000269|PubMed:1659948, ECO:0000269|PubMed:20076800}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. {ECO:0000269|PubMed:15596759, ECO:0000269|PubMed:18046642, ECO:0000269|PubMed:20522878}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise. {ECO:0000269|PubMed:10218481, ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:16832098, ECO:0000269|PubMed:17212350, ECO:0000269|PubMed:17998485, ECO:0000269|PubMed:18203179, ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:19015483, ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:8058156, ECO:0000269|PubMed:9392583}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS16 is characterized by fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation. {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22A, classic (CMYO22A) [MIM:620351]: A form of congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22A is an autosomal recessive form characterized by fetal hypokinesia, polyhydramnios, and severe neonatal hypotonia associated with respiratory insufficiency. Affected individuals who survive the neonatal period have delayed motor development, difficulty walking, proximal muscle weakness of the upper and lower limbs, facial and neck muscle weakness, easy fatigability, and mild limb contractures or foot deformities. {ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:28262468, ECO:0000269|PubMed:36090556}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22B, severe fetal (CMYO22B) [MIM:620369]: A severe congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22B is an autosomal recessive form characterized by onset in utero. Affected individuals show fetal akinesia, and develop fetal hydrops with pulmonary hypoplasia, severe joint contractures, and generalized muscle hypoplasia. Death occurs in utero or soon after birth. {ECO:0000269|PubMed:26700687}. The disease is caused by variants affecting the gene represented in this entry.

DB05096

NA

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix

A

50355.5

445

0.11

38.26

6.52

-1.53

-6.25

UMPS

Homo sapiens (Human)

Uridine 5'-monophosphate synthase; UMP synthase

Purine/pyrimidine phosphoribosyltransferase family; OMP decarboxylase family

Pentosyltransferase

Catalyses the formation of uridine monophosphate (UMP), an energy-carrying molecule in many important biosynthetic pathways.

Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and intellectual disability. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. {ECO:0000269|PubMed:9042911}. The disease is caused by variants affecting the gene represented in this entry.

DB02890; DB00544

P54764; P11172-1

NA

3D-structure; Acetylation; Alternative splicing; Decarboxylase; Disease variant; Glycosyltransferase; Lyase; Multifunctional enzyme; Phosphoprotein; Proteomics identification; Pyrimidine biosynthesis; Reference proteome; Transferase

A,B

55844

514

0.06

22.7

6.44

-2.99

-6.24

UCHL1

Homo sapiens (Human)

Ubiquitin thiolesterase L1; Ubiquitin carboxyl-terminal hydrolase isozyme L1; Ubiquitin carboxy-terminal hydrolase L1; UCH-L1; PGP9.5; PGP 9.5; Neuron cytoplasmic protein 9.5

Peptidase C12 family

Peptidase

Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

Parkinson disease 5 (PARK5) [MIM:613643]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia. {ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:9774100}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 79A, autosomal dominant, with ataxia (SPG79A) [MIM:620221]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79A is a slowly progressive form characterized by late-onset spastic ataxia, neuropathy, and often optic atrophy. {ECO:0000269|PubMed:35986737}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 79B, autosomal recessive (SPG79B) [MIM:615491]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79B is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction. {ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:28007905}. The disease is caused by variants affecting the gene represented in this entry.

DB12695

P63010-2; P05067; P05067-2; Q8N6T3-3; P18847; Q9H1Y0; O15392; Q8WUW1; P83916; P11802; Q00535; Q9UNS2; Q92905; P00533; O60739; Q8TC29; Q9UI08-2; Q8WVV9-3; Q14164; Q6DN90-2; Q96JM7-2; P13473-2; Q9BYZ2; O95777; A4FUJ8; Q15843; O15381-5; Q9BR81; Q13113; P62826; Q8TAI7; Q9ULX5; Q15554-4; Q9NYB0; P04637; Q9Y4K3; P19474; Q9BSL1; Q7KZS0; P61086; Q9UK80; Q86WB0-2

EC 3.4.19.12

3D-structure; Cytoplasm; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Glycoprotein; Hereditary spastic paraplegia; Hydrolase; Lipoprotein; Membrane; Neurodegeneration; Oxidation; Parkinson disease; Parkinsonism; Phosphoprotein; Prenylation; Protease; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation pathway

A,B

33389.8

298

0.07

38.69

5.51

-7.88

-6.24

GABBR1

Homo sapiens (Human)

NA

GPRC3B;GPR51

G-protein coupled receptor 3 family, GABA-B receptor subfamily

Signaling protein / antagonist

G-protein coupled GABA receptor activity.

Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS) [MIM:617903]: An autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability. {ECO:0000269|PubMed:26740508, ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 59 (DEE59) [MIM:617904]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy. {ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29100083, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.

DB08891; DB08892; DB00181; DB00363; DB02530; DB05010; DB09072

Q9UBS5; Q9UBS5-2; P46459; Q86UR5

NA

3D-structure; Cell membrane; Coiled coil; Direct protein sequencing; Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; Intellectual disability; Membrane; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transducer; Transmembrane; Transmembrane helix

A

46502.1

408

0.12

50.05

5.78

-5.62

-6.23

metF

Escherichia coli (strain K12)

NA

b3941;JW3913

Methylenetetrahydrofolate reductase family

Oxidoreductase

FAD binding.Methylenetetrahydrofolate reductase (NAD(P)H) activity.

Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR) [MIM:301220]: An X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines. {ECO:0000269|PubMed:27019227}. The disease is caused by variants affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication. {ECO:0000269|PubMed:27019227}.; DISEASE: Van Esch-O'Driscoll syndrome (VEODS) [MIM:301030]: An X-linked recessive syndrome characterized by different degrees of intellectual disability, moderate to severe short stature, microcephaly, hypogonadism, and variable congenital malformations. {ECO:0000269|PubMed:31006512}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

1.5.1.54

3D-structure; Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD; Oxidoreductase; Reference proteome

A,C,E

30855.9

274

0.09

27.54

5.84

-4.61

-6.24

DRD2

Homo sapiens (Human)

Dopamine receptor 2; D(2) dopamine receptor

G-protein coupled receptor 1 family

GPCR rhodopsin

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.

Congenital sucrase-isomaltase deficiency (CSID) [MIM:222900]: Autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI. {ECO:0000269|PubMed:10903344, ECO:0000269|PubMed:11340066, ECO:0000269|PubMed:14724820, ECO:0000269|PubMed:16329100, ECO:0000269|PubMed:8609217}. The disease is caused by variants affecting the gene represented in this entry.

DB01614; DB01063; DB01425; DB00915; DB06288; DB05964; DB00543; DB00182; DB04599; DB00714; DB01238; DB14185; DB09207; DB06216; DB04889; DB04888; DB05687; DB09223; DB04857; DB09128; DB01200; DB09018; DB00490; DB00248; DB06016; DB01038; DB00477; DB01239; DB00568; DB00363; DB01151; DB11274; DB13345; DB00320; DB01184; DB00988; DB00450; DB11275; DB01049; DB00696; DB01175; DB09194; DB00875; DB00623; DB04842; DB00502; DB04946; DB00458; DB04924; DB12579; DB01221; DB00555; DB01235; DB00589; DB00408; DB06077; DB08815; DB00934; DB09224; DB01043; DB00933; DB01403; DB01233; DB06148; DB00805; DB01618; DB08804; DB05766; DB00540; DB06229; DB00334; DB01267; DB12061; DB00715; DB01186; DB08922; DB00850; DB01100; DB09286; DB01621; DB12478; DB00413; DB00433; DB00420; DB01069; DB00777; DB01224; DB09097; DB12518; DB00409; DB00734; DB01549; DB00268; DB05271; DB06454; DB06144; DB00391; DB06477; DB04844; DB12093; DB00372; DB01622; DB00679; DB01623; DB13025; DB00831; DB00508; DB00726; DB06109; DB01392; DB00246; DB09225; DB01624

Q9NRI5; P14416; Q01959

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Golgi apparatus; Lipoprotein; Membrane; Palmitate; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

B,C

24300.3

209

0.13

40.14

4.97

-7.83

-6.23

FLT4

Homo sapiens (Human)

NA

VEGFR3

Protein kinase superfamily, Tyr protein kinase family, CSF-1/PDGF receptor subfamily

Transferase

ATP binding.Growth factor binding.Protein homodimerization activity.Protein phosphatase binding.Transmembrane receptor protein tyrosine kinase activity.Vascular endothelial growth factor-activated receptor activity.VEGF-C-activated receptor activity.

Lymphatic malformation 1 (LMPHM1) [MIM:153100]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM1 is an autosomal dominant form with variable expression and severity. Onset is usually at birth or in early childhood but can occur later. Affected individuals manifest lymphedema, predominantly in the lower limbs, and hypoplasia of lymphatic vessels. Additional features are hemangioma and nail dysplasia or papillomatosis. {ECO:0000269|PubMed:10835628, ECO:0000269|PubMed:10856194, ECO:0000269|PubMed:12881528, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:16924388, ECO:0000269|PubMed:16965327, ECO:0000269|PubMed:17458866, ECO:0000269|PubMed:19289394, ECO:0000269|PubMed:26091405, ECO:0000269|PubMed:9817924}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hemangioma, capillary infantile (HCI) [MIM:602089]: A condition characterized by dull red, firm, dome-shaped hemangiomas, sharply demarcated from surrounding skin, usually presenting at birth or occurring within the first two or three months of life. They result from highly proliferative, localized growth of capillary endothelium and generally undergo regression and involution without scarring. {ECO:0000269|PubMed:11807987}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases.; DISEASE: Congenital heart defects, multiple types, 7 (CHTD7) [MIM:618780]: An autosomal dominant disorder with incomplete penetrance characterized by congenital developmental abnormalities involving structures of the heart. Common defects include tetralogy of Fallot, pulmonary stenosis or atresia, absent pulmonary valve, right aortic arch, double aortic arch, and major aortopulmonary collateral arteries. {ECO:0000269|PubMed:28991257, ECO:0000269|PubMed:30232381}. The disease is caused by variants affecting the gene represented in this entry.

DB06626; DB05932; DB12010; DB11679; DB06101; DB09078; DB06080; DB09079; DB06589; DB08896; DB15685; DB00398; DB01268; DB05075; DB11800; DB04879

P08238; P35968; P49767

2.7.10.1

3D-structure; Alternative splicing; Angiogenesis; ATP-binding; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase

A

24029.2

213

0.1

47.75

8.34

2.35

-6.23