TH

Homo sapiens (Human)

Tyrosine 3-hydroxylase; TH

Biopterin-dependent aromatic amino acid hydroxylase family

Paired donor oxygen oxidoreductase

Plays an important role in the physiology of adrenergic neurones.

Segawa syndrome autosomal recessive (ARSEGS) [MIM:605407]: A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA. {ECO:0000269|PubMed:10585338, ECO:0000269|PubMed:11196107, ECO:0000269|PubMed:11246459, ECO:0000269|PubMed:15505183, ECO:0000269|PubMed:15747353, ECO:0000269|PubMed:16049992, ECO:0000269|PubMed:17696123, ECO:0000269|PubMed:18058633, ECO:0000269|PubMed:18554280, ECO:0000269|PubMed:19491146, ECO:0000269|PubMed:20056467, ECO:0000269|PubMed:20430833, ECO:0000269|PubMed:21940685, ECO:0000269|PubMed:22264700, ECO:0000269|PubMed:22815559, ECO:0000269|PubMed:23762320, ECO:0000269|PubMed:23939262, ECO:0000269|PubMed:24753243, ECO:0000269|PubMed:7814018, ECO:0000269|PubMed:8528210, ECO:0000269|PubMed:8817341, ECO:0000269|PubMed:9613851, ECO:0000269|PubMed:9703425}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: May play a role in the pathogenesis of Parkinson disease (PD). A genome-wide copy number variation analysis has identified a 34 kilobase deletion over the TH gene in a PD patient but not in any controls. {ECO:0000269|PubMed:20809526}.

DB03552; DB04400; DB00765; DB00120; DB00360; DB00135

P29762; P61978-2; Q99750; P08651-5; O75928-2; Q9UHX1-2; P0DJD3-2; P07101-3; Q9UJ04; C9J7I0; Q5MCW4

EC 1.14.16.2

3D-structure; Alternative splicing; Catecholamine biosynthesis; Cell projection; Cytoplasm; Cytoplasmic vesicle; Disease variant; Dystonia; Iron; Metal-binding; Monooxygenase; Neurotransmitter biosynthesis; Nucleus; Oxidoreductase; Parkinson disease; Parkinsonism; Phosphoprotein; Proteomics identification; Reference proteome; Synapse

A,B,C,D

34997

306

0.12

42.59

5.32

-12.31

-5.81

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

-5.81

CTH

Homo sapiens (Human)

Gamma-cystathionase; Cysteine-protein sulfhydrase

Trans-sulfuration enzymes family

NA

Catalyzes the last step in the trans-sulfuration pathway from methionine to cysteine. Has broad substrate specificity. Converts cystathionine to cysteine, ammonia and 2-oxobutanoate. Converts two cysteine molecules to lanthionine and hydrogen sulfide. Can also accept homocysteine as substrate. Specificity depends on the levels of the endogenous substrates. Generates the endogenous signaling molecule hydrogen sulfide (H2S), and so contributes to the regulation of blood pressure. Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function.

Cystathioninuria (CSTNU) [MIM:219500]: Autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. {ECO:0000269|PubMed:12574942, ECO:0000269|PubMed:18476726}. The disease is caused by variants affecting the gene represented in this entry.

DB02328; DB03928; DB00151; DB04217; DB00114

P32929; Q96NT3; Q96NT3-2; Q96HA8; Q6P9E2

EC 4.4.1.1

3D-structure; Alternative splicing; Amino-acid biosynthesis; Calmodulin-binding; Cysteine biosynthesis; Cytoplasm; Disease variant; Lipid metabolism; Lyase; Proteomics identification; Pyridoxal phosphate; Reference proteome

A,B,C,D

86026

782

0.08

32.4

6.27

-9.46

-5.81

AVPR1A

Homo sapiens (Human)

NA

AVPR1

G-protein coupled receptor 1 family, Vasopressin/oxytocin receptor subfamily

Sugar binding protein

Peptide binding.Peptide hormone binding.Protein kinase C binding.V1A vasopressin receptor binding.Vasopressin receptor activity.

Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. {ECO:0000269|PubMed:10394368}.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:9753710}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Lipodystrophy, familial partial, 3 (FPLD3) [MIM:604367]: A form of lipodystrophy characterized by marked loss of subcutaneous fat from the extremities. Facial adipose tissue may be increased, decreased or normal. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia. {ECO:0000269|PubMed:11788685, ECO:0000269|PubMed:12453919}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Glioma 1 (GLM1) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:10851250}. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.

DB09059; DB00872; DB00035; DB00093; DB14642; DB16279; DB05452; DB13929; DB02638; DB06212; DB00067

P25106

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

M,N

40697.6

371

0.1

20.94

5.07

-9.93

-5.81

RRM2

Homo sapiens (Human)

NA

RR2

Ribonucleoside diphosphate reductase small chain family

Oxidoreductase

Metal ion binding.Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.

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.

DB00242; DB05260; DB05801; DB05003; DB05428

P41002; Q9UM11; P23921; O00560

1.17.4.1

3D-structure; Alternative splicing; Cytoplasm; Deoxyribonucleotide synthesis; Iron; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,B,C,D

33579.4

286

0.14

43.7

5.12

-12.86

-5.81

CASP3

Homo sapiens (Human)

Yama protein; SREBP cleavage activity 1; SCA-1; Protein Yama; Cysteine protease CPP32; Caspase 3; CPP32; CPP-32; CASP-3; Apopain

Peptidase C14A family

Peptidase

At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Involved in the activation cascade of caspases responsible for apoptosis execution.

Smith-Kingsmore syndrome (SKS) [MIM:616638]: An autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features. {ECO:0000269|PubMed:25851998, ECO:0000269|PubMed:26542245, ECO:0000269|PubMed:27830187}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells. {ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:25878179, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187}. The disease is caused by variants affecting the gene represented in this entry.

DB08498; DB08497; DB08213; DB06862; DB08251; DB03124; DB08229; DB00945; DB05408; DB13751; DB06255; DB07696; DB01017; DB08499; DB12843; DB13048; DB00282; DB12709

O43823; Q9Y243; P05067; P54252; P55212; P55211; Q14203-5; P42858; Q00987; O60551; P09874; Q5JUK2; P10599; Q9BYP7; P98170

EC 3.4.22.56

3D-structure; Acetylation; Apoptosis; Cytoplasm; Direct protein sequencing; Hydrolase; Phosphoprotein; Protease; Proteomics identification; Reference proteome; S-nitrosylation; Thiol protease; Ubl conjugation; Zymogen

A

27483.1

239

0.11

38.09

8.39

3.03

-5.81

PPIG

Homo sapiens (Human)

NA

NA

NA

Isomerase

Cyclosporin A binding.Peptidyl-prolyl cis-trans isomerase activity.RNA binding.

Intellectual developmental disorder, autosomal dominant 6, with or without seizures (MRD6) [MIM:613970]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features. {ECO:0000269|PubMed:20890276, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:28095420, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 27 (DEE27) [MIM:616139]: 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. {ECO:0000269|PubMed:24272827, ECO:0000269|PubMed:27839871, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:38538865}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A chromosomal aberrations involving GRIN2B has been found in patients with intellectual disability. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.

DB00172

Q8N7W2-2; Q8NHQ1; O75553; Q9UI36-2; Q96C98; Q8NC69; P17931; Q6NVH9; Q15365; Q9UL42; Q96CD2; Q14498; Q16637; Q12800; Q9NVV9; PRO_0000037309 [P0C6X7]

5.2.1.8

3D-structure; Alternative splicing; Isomerase; Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Rotamase; Ubl conjugation

A

19125.4

173

0.1

26.46

7.14

0.24

-5.81

SGPL1

Homo sapiens (Human)

hSPL; Sphingosine-1-phosphate aldolase; SPL 1; SP-lyase 1; S1PL; KIAA1252

Group II decarboxylase family, Sphingosine-1-phosphate lyase subfamily

Carbon-carbon lyase

Elevates stress-induced ceramide production and apoptosis. Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP. Seems to play a role in establishing neuronal contact sites and axonal maintenance. Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine.

RENI syndrome (RENI) [MIM:617575]: An autosomal recessive, steroid-resistant nephrotic syndrome that manifests in infancy or early childhood, and progresses to end-stage renal failure within a few years. Additional clinical features include ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects. In rare cases, patients present with isolated primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. {ECO:0000269|PubMed:28165339, ECO:0000269|PubMed:28165343, ECO:0000269|PubMed:28181337, ECO:0000269|PubMed:30090628}. The disease is caused by variants affecting the gene represented in this entry.

DB00114

Q92482; O43315; Q92843; Q6PL45-2; Q8NHW4; Q8N6F1-2; P52803; Q9UKR5; Q7L5A8; Q8N128-2; Q14802-3; P30519; Q01628; Q9NX47; Q6ZSS7; P30301; Q8IY49-2; Q9NXK6; Q04941; Q5VZY2; Q5GAN6; Q5QGT7; Q8TAC9; Q99726; P02808; Q86WV6; Q12846; Q9UNK0; Q96HP8; Q9NWH2; Q5BJF2; O14817; A5PKU2; Q53HI1

EC 4.1.2.27

3D-structure; Acetylation; Apoptosis; Disease variant; Endoplasmic reticulum; Lipid metabolism; Lyase; Membrane; Nitration; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Signal-anchor; Sphingolipid metabolism; Transmembrane; Transmembrane helix

A,B

97521.7

887

0.1

32.99

8.97

18.32

-5.81

WARS2

Homo sapiens (Human)

NA

NA

Class-I aminoacyl-tRNA synthetase family

Ligase / antibiotic

ATP binding.Tryptophan-tRNA ligase activity.

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) [MIM:617710]: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals. {ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:28650581, ECO:0000269|PubMed:28905505, ECO:0000269|PubMed:30920170, ECO:0000269|PubMed:35074316}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinsonism-dystonia 3, childhood-onset (PKDYS3) [MIM:619738]: An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. {ECO:0000269|PubMed:29120065, ECO:0000269|PubMed:31970218, ECO:0000269|PubMed:34890876}. The disease is caused by variants affecting the gene represented in this entry.

DB00150

NA

6.1.1.2

3D-structure; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Disease variant; Dystonia; Ligase; Mitochondrion; Nucleotide-binding; Parkinsonism; Primary mitochondrial disease; Protein biosynthesis; Proteomics identification; Reference proteome; Transit peptide

A,B

36376.7

327

0.06

51.57

8.75

4.55

-5.81

CMA1

Homo sapiens (Human)

Mast cell protease I; CYH; Alpha-chymase

Peptidase S1 family, Granzyme subfamily

Peptidase

Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.

Weaver syndrome (WVS) [MIM:277590]: A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand. {ECO:0000269|PubMed:22177091, ECO:0000269|PubMed:22190405, ECO:0000269|PubMed:23239504, ECO:0000269|PubMed:26694085, ECO:0000269|PubMed:28229514}. The disease is caused by variants affecting the gene represented in this entry.

DB03814; DB04016; DB07680; DB03297

NA

EC 3.4.21.39

3D-structure; Alternative splicing; Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; Protease; Proteomics identification; Reference proteome; Secreted; Serine protease; Signal; Zymogen

A

23715.1

215

0.07

37.79

9.51

11.49

-5.81

PDE3B

Homo sapiens (Human)

cGMPinhibited 3',5'cyclic phosphodiesterase B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B; Cyclic GMPinhibited phosphodiesterase B; Cyclic GMP-inhibited phosphodiesterase B; CGIPDE1; CGIPDE B; CG

Cyclic nucleotide phosphodiesterase family, PDE3 subfamily

Phosphoric diester hydrolase

May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. {ECO:0000269|PubMed:18184961, ECO:0000269|PubMed:18378852, ECO:0000269|PubMed:19208626, ECO:0000269|PubMed:22367913}. The disease is caused by variants affecting the gene represented in this entry.

DB07954; DB01640; DB01427; DB00201; DB01970; DB01113; DB09283

O60760; Q8TBB1; P48736; Q5UE93; O95398

EC 3.1.4.17

3D-structure; Alternative splicing; Angiogenesis; cAMP; cGMP; Hydrolase; Magnesium; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A

41872.2

364

0.11

48.97

5.64

-11.84

-5.8

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

-5.8

TNKS2

Homo sapiens (Human)

Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribos

ARTD/PARP family

Glycosyltransferases

Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. {ECO:0000269|PubMed:30290153}. The disease is caused by variants affecting the gene represented in this entry.

NA

O15084; Q7Z6K5-1; O15169; Q9NWV8; P11274; Q13698; Q9NRI5; Q6V0I7; Q9NWT6; P14652; Q9UIQ6; Q14980; Q9BZL4; Q92698; P78314; O43815; P54274; Q9C0C2; Q9UHP3; Q06649

EC 2.4.2.30

3D-structure; ADP-ribosylation; ANK repeat; Chromosome; Cytoplasm; Glycosyltransferase; Golgi apparatus; Hydroxylation; Membrane; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Proteomics identification; Reference proteome; Repeat; Telomere; Transferase; Ubl conjugation; Wnt signaling pathway; Zinc

A

23695.5

208

0.11

47.61

8.28

2.88

-5.8

Fung ILS1

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Fung Isoleucyl-tRNA synthetase; Fung Isoleucine--tRNA ligase, cytoplasmic; Fung IleRS

Class-I aminoacyl-tRNA synthetase family

Carbon-oxygen ligase

Has aminoacyl-tRNA editing and isoleucine-tRNA ligase activity.

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) [MIM:617333]: An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures. {ECO:0000269|PubMed:27939639, ECO:0000269|PubMed:27939640}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 6.1.1.5

3D-structure; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Direct protein sequencing; Isopeptide bond; Ligase; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; Reference proteome; Ubl conjugation

A

105860

919

0.12

37.01

5.73

-14.6

-5.81

BRD9

Homo sapiens (Human)

Rhabdomyosarcoma antigen MU-RMS-40.8

NA

Bromodomain

Plays a role in chromatin remodeling and regulation of transcription. Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.

Major depressive disorder (MDD) [MIM:608516]: A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. {ECO:0000269|PubMed:15229186}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

NA

Q7Z7H3; Q7Z7H3

NA

3D-structure; Acetylation; Alternative splicing; Bromodomain; Chromatin regulator; Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Ubl conjugation

A

11491.3

99

0.13

13.58

9.24

3.8

-5.81

USP30

Homo sapiens (Human)

Deubiquitinating enzyme 30; Ubiquitin thioesterase 30; Ubiquitin-specific-processing protease 30; Ub-specific protease 30

Peptidase C19 family

Peptidase

Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy. Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate in mitophagic signaling. Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65'. Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (By similarity).

Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269|PubMed:11498583}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves. {ECO:0000269|PubMed:15060842, ECO:0000269|PubMed:15911806, ECO:0000269|PubMed:18521183}. The disease is caused by variants affecting the gene represented in this entry.

NA

P54253; Q6NTF9-3

EC 3.4.19.12

3D-structure; Hydrolase; Isopeptide bond; Membrane; Mitochondrion; Mitochondrion outer membrane; Protease; Proteomics identification; Reference proteome; Thiol protease; Transmembrane; Transmembrane helix; Ubl conjugation; Ubl conjugation pathway

A,B

43456.9

379

0.09

50.2

6.43

-4.37

-5.81

FOLR2

Homo sapiens (Human)

Placental folate-binding protein; Folate receptor, fetal/placental; Folate receptor type-beta; Folate receptor 2; FR-beta; FOLR2

Folate receptor family

Folate receptor

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release.

Acute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:17236137, ECO:0000269|PubMed:2063868}. The disease is caused by variants affecting the gene represented in this entry.

DB00158; DB00563; DB05168

NA

NA

3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond; Folate-binding; Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Proteomics identification; Receptor; Reference proteome; Secreted; Signal; Transport

A

23841.6

205

0.12

56.78

7.92

2.58

-5.81

MET

Homo sapiens (Human)

NA

NA

Protein kinase superfamily, Tyr protein kinase family

Transferase / transferase inhibitor

ATP binding.Hepatocyte growth factor-activated receptor activity.Identical protein binding.Phosphatidylinositol-4,5-bisphosphate 3-kinase activity.Protein phosphatase binding.Protein tyrosine kinase activity.Ras guanyl-nucleotide exchange factor activity.

Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.; DISEASE: Defects in MET may be associated with gastric cancer.; DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269|PubMed:9927037}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. {ECO:0000269|PubMed:10327054, ECO:0000269|PubMed:10417759, ECO:0000269|PubMed:10433944, ECO:0000269|PubMed:9140397, ECO:0000269|PubMed:9563489}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes.; DISEASE: MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.; DISEASE: Deafness, autosomal recessive, 97 (DFNB97) [MIM:616705]: A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:25941349}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Osteofibrous dysplasia (OSFD) [MIM:607278]: A congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula. {ECO:0000269|PubMed:26637977}. Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease-associated variants identified in 4 families cause the deletion of exon 14. This results in the exclusion of an ubiquitination target site within the cytoplasmic domain, hence in protein stabilization. The persistent presence of MET at the cell surface in conditions of ligand-dependent activation retards osteoblastic differentiation. {ECO:0000269|PubMed:26637977}.; DISEASE: Arthrogryposis, distal, 11 (DA11) [MIM:620019]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA11 is an autosomal dominant form characterized mainly by camptodactyly. Other features include absent flexion creases and limited forearm supination. {ECO:0000269|PubMed:30777867}. The disease may be caused by variants affecting the gene represented in this entry.

DB06896; DB08791; DB06997; DB07969; DB08079; DB16695; DB12742; DB12267; DB08875; DB11791; DB08865; DB12010; DB02152; DB07369; DB06995; DB06314; DB01268; DB15133; DB12200; DB11800

P22681; Q96EY1; Q96EY1-2; P00533; P09769; P14210; P14210-6; O15357; P35968; P06239; P07948; P08581; P41218; P15941; P16333; O43639; Q16288; P27986; O00459; Q92569; P19174; O43157; O15031; Q9ULL4; Q8TCU6; P18031; Q06124; P23467; Q12913; Q16827; P20936; Q9UQQ2; O60880; O14796; Q9NP31; Q8N5H7; Q15464; P29353; P98077; Q6S5L8; Q96IW2; Q9H6Q3; O75159; O14544; P12931; Q9ULZ2; P43405; P42680; Q9HBL0; Q63HR2; Q68CZ2; Q9UKW4; P07947; P43403; Q08048; P0DQD2; P35918; Q00944

2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; Deafness; Disease variant; Disulfide bond; Glycoprotein; Kinase; Membrane; Non-syndromic deafness; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

32760.8

289

0.1

37.12

8.79

5.68

-5.8

PDXK

Homo sapiens (Human)

Pyridoxine kinase; PDXK

Pyridoxine kinase family

Kinase

Required for synthesisof pyridoxal-5-phosphate from vitamin B6.

Neuropathy, hereditary motor and sensory, 6C, with optic atrophy (HMSN6C) [MIM:618511]: An autosomal recessive neurologic disorder characterized by childhood onset of axonal, sensorimotor polyneuropathy affecting mainly the lower limbs, and adult-onset optic atrophy. Clinical features include progressive distal muscle weakness and atrophy, significant standing and walking difficulties, areflexia, neurogenic pain and progressive visual impairment. {ECO:0000269|PubMed:31187503}. The disease is caused by variants affecting the gene represented in this entry.

DB04776; DB03909; DB04770; DB00147; DB00165

NA

EC 2.7.1.35

3D-structure; Acetylation; Alternative splicing; ATP-binding; Charcot-Marie-Tooth disease; Cobalt; Cytoplasm; Disease variant; Kinase; Magnesium; Manganese; Metal-binding; Neurodegeneration; Neuropathy; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Sodium; Transferase; Zinc

A,B

34370.1

305

0.07

39.92

6.16

-3.37

-5.81

GSTP1

Homo sapiens (Human)

GSTP11; GSTP1-1; GST3; GST classpi; GST class-pi; FAEES3

GST superfamily, Pi family

Alkyl aryl transferase

Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB01834; DB03814; DB00316; DB14001; DB00321; DB01008; DB04972; DB00958; DB00291; DB02633; DB00515; DB01242; DB00363; DB11672; DB14635; DB14002; DB03619; DB11831; DB00903; DB00773; DB06246; DB05460; DB00143; DB03310; DB03003; DB13014; DB00526; DB14924; DB08370; DB03686; DB04132; DB01915; DB07849; DB00197; DB00163

Q6UY14-3; Q92624; Q9BWT7; A8MQ03; Q9NRD0; Q5TD97; P49639; Q15323; Q14525; O76011; P78385; Q07627; Q8IUG1; P60409; P60411; Q9BYR8; Q9BYR6; Q3LI66; Q9P2M1; Q5JR59-3; Q7Z3S9; P0DPK4; P22735; Q12933; Q8N720

EC 2.5.1.18

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; Mitochondrion; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transferase

A,B

46333.6

417

0.1

30.67

5.44

-5.73

-5.81