TPMT

Homo sapiens (Human)

NA

NA

Class I-like SAM-binding methyltransferase superfamily, TPMT family

Transferase

Thiopurine S-methyltransferase activity.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB00993; DB00436; DB01327; DB01033; DB01250; DB01021

Q8TAP4-4; Q15047-2; P61981

2.1.1.67

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Methyltransferase; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A

25971.5

229

0.12

32.58

6.74

-0.6

-7.32

NAGLU

Homo sapiens (Human)

UFHSD1; NAGLU; NAG; N-acetyl-alpha-glucosaminidase; Alpha-N-acetylglucosaminidase82 kDa form; Alpha-N-acetylglucosaminidase77 kDa form

Glycosyl hydrolase 89 family

Glycosylase

Involved in the degradation of heparan sulfate.

Mucopolysaccharidosis 3B (MPS3B) [MIM:252920]: A form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. {ECO:0000269|PubMed:10094189, ECO:0000269|PubMed:11068184, ECO:0000269|PubMed:11153910, ECO:0000269|PubMed:11286389, ECO:0000269|PubMed:11793481, ECO:0000269|PubMed:11836372, ECO:0000269|PubMed:12202988, ECO:0000269|PubMed:14984474, ECO:0000269|PubMed:15933803, ECO:0000269|PubMed:16151907, ECO:0000269|PubMed:28101780, ECO:0000269|PubMed:9443875, ECO:0000269|PubMed:9443878, ECO:0000269|PubMed:9832037, ECO:0000269|PubMed:9950362}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease, axonal, 2V (CMT2V) [MIM:616491]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2V is an autosomal dominant sensory neuropathy with late onset. The main clinical feature is recurrent leg pain that progresses to constant painful paraesthesias in the feet and later the hands. As it evolves, some patients develop a mild sensory ataxia. {ECO:0000269|PubMed:25818867}. The disease is caused by variants affecting the gene represented in this entry.

DB06773; DB00141

NA

EC 3.2.1.50

3D-structure; Charcot-Marie-Tooth disease; Direct protein sequencing; Disease variant; Glycoprotein; Glycosidase; Hydrolase; Lysosome; Mucopolysaccharidosis; Neurodegeneration; Neuropathy; Proteomics identification; Reference proteome; Signal

A

80206.3

720

0.13

41.59

6.28

-4.09

-7.33

GHRL

Homo sapiens (Human)

UNQ524/PRO1066; Motilin-related peptide; M46 protein; Growth hormone secretagogue; Growth hormone releasing peptide; Gastric peptide ghrelin; GHRL

Motilin family

NA

Specific ligand for the growth hormone secretagogue receptor type 1 (ghsr) inducing the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion.Involved in growth regulation.

Neurodevelopmental disorder with structural brain anomalies and dysmorphic facies (NEDBAF) [MIM:618577]: An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability, poor language, seizures, dysmorphic features, and thin corpus callosum. {ECO:0000269|PubMed:29276006, ECO:0000269|PubMed:30293988}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UMX0; Q9UMX0-2; Q9UHD9

NA

3D-structure; Alternative splicing; Amidation; Direct protein sequencing; Hormone; Lipoprotein; Proteomics identification; Reference proteome; Secreted; Signal

C,R

34053.1

300

0.14

38.34

9.3

11.02

-7.32

USP14

Homo sapiens (Human)

Ubiquitin-specific-processing protease 14; Ubiquitin thioesterase 14; TGT; Deubiquitinating enzyme 14

Peptidase C19 family, USP14/UBP6 subfamily

Peptidase

Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation. Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins.

Hypophosphatemic rickets, autosomal dominant (ADHR) [MIM:193100]: A disease characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses. {ECO:0000269|PubMed:11062477, ECO:0000269|PubMed:11409890, ECO:0000269|PubMed:16638743}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Tumoral calcinosis, hyperphosphatemic, familial, 2 (HFTC2) [MIM:617993]: A form of hyperphosphatemic tumoral calcinosis, a rare autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients have recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement. {ECO:0000269|PubMed:15590700, ECO:0000269|PubMed:16030159, ECO:0000269|PubMed:16151858, ECO:0000269|PubMed:24680727}. The disease is caused by variants affecting the gene represented in this entry.

DB12695

Q08209

EC 3.4.19.12

3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Hydrolase; Immunity; Innate immunity; Membrane; Phosphoprotein; Protease; Proteasome; Proteomics identification; Reference proteome; Thiol protease; Ubl conjugation pathway

A

38476.7

335

0.1

61.05

5.6

-4.84

-7.32

DYRK2

Homo sapiens (Human)

Dual specificity tyrosine-phosphorylation-regulated kinase 2

Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MNB/DYRK subfamily

Kinase

Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth.

Bone marrow failure and diabetes mellitus syndrome (BMFDMS) [MIM:620044]: A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFDMS is an autosomal recessive form characterized by various degrees of bone marrow failure, ranging from dyserythropoiesis to bone marrow aplasia, with onset in infancy or early childhood, and non-autoimmune insulin-dependent diabetes mellitus appearing in the first or second decades. Many patients show pigmentary skin abnormalities and short stature. {ECO:0000269|PubMed:28073829, ECO:0000269|PubMed:35611808, ECO:0000269|PubMed:35931051}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NR20; Q13422; Q9BQD3; Q9BRK4; P23497; O43379; P62258; Q96C00

EC 2.7.12.1

3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm; Kinase; Magnesium; Manganese; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase; Ubl conjugation; Ubl conjugation pathway

A

46422.1

407

0.09

44.91

9.09

12.37

-7.33

TGFBR1

Homo sapiens (Human)

Type I TGFbeta receptor kinase; Transforming growth factor-beta receptor type I; TbetaRI; TbetaR-I; TGFR-1; TGF-beta type I receptor; TGF-beta receptor type-1; Serine/threonine-protein kinase receptor

Protein kinase superfamily, TKL Ser/Thr protein kinase family, TGFB receptor subfamily

Kinase

Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.

Loeys-Dietz syndrome 1 (LDS1) [MIM:609192]: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. {ECO:0000269|PubMed:15731757, ECO:0000269|PubMed:16596670, ECO:0000269|PubMed:16791849, ECO:0000269|PubMed:16928994, ECO:0000269|PubMed:19883511, ECO:0000269|PubMed:22113417}. The disease is caused by variants affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 by the OMIM resource. {ECO:0000269|PubMed:16791849}.; DISEASE: Multiple self-healing squamous epithelioma (MSSE) [MIM:132800]: A disorder characterized by multiple skin tumors that undergo spontaneous regression. Tumors appear most often on sun-exposed regions, are locally invasive, and undergo spontaneous resolution over a period of months leaving pitted scars. {ECO:0000269|PubMed:21358634}. The disease is caused by variants affecting the gene represented in this entry.

DB07267; DB04480; DB03921; DB12010; DB08450; DB07152; DB04434

P62942; P01137; P63104; PRO_0000045599 [Q99IB8]; P02750

EC 2.7.11.30

3D-structure; Alternative splicing; Aortic aneurysm; Apoptosis; ATP-binding; Cell junction; Cell membrane; Craniosynostosis; Differentiation; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Serine/threonine-protein kinase; Signal; Tight junction; Transferase; Transmembrane; Transmembrane helix; Ubl conjugation

A

33706.4

295

0.09

43.4

8.8

5.17

-7.32

SLC40A1

Homo sapiens (Human)

SLC11A3; MSTP079; IREG1; Ferroportin-1; FPN1

Ferroportin (FP) (TC 2.A.100) family, SLC40A subfamily

Ferroportin protein

Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin). May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation.

Hemochromatosis 4 (HFE4) [MIM:606069]: A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading. {ECO:0000269|PubMed:10747949, ECO:0000269|PubMed:11431687, ECO:0000269|PubMed:11518736, ECO:0000269|PubMed:12091366, ECO:0000269|PubMed:12091367, ECO:0000269|PubMed:12123233, ECO:0000269|PubMed:12406098, ECO:0000269|PubMed:12730114, ECO:0000269|PubMed:12857562, ECO:0000269|PubMed:12865285, ECO:0000269|PubMed:12873829, ECO:0000269|PubMed:14757427, ECO:0000269|PubMed:15338274, ECO:0000269|PubMed:15466004, ECO:0000269|PubMed:15692071, ECO:0000269|PubMed:16351644, ECO:0000269|PubMed:29237594, ECO:0000269|PubMed:30247984}. The disease is caused by variants affecting the gene represented in this entry.

DB13257; DB14520

P05067

NA

3D-structure; Cell membrane; Disease variant; Glycoprotein; Ion transport; Iron; Iron transport; Membrane; Metal-binding; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport; Ubl conjugation

A

46824.1

429

0.1

31.46

8.37

3

-7.32

FFAR1

Homo sapiens (Human)

NA

GPR40

G-protein coupled receptor 1 family

Fatty acid binding protein / hydrolase

Bioactive lipid receptor activity.G-protein coupled receptor activity.Guanyl-nucleotide exchange factor activity.Lipid binding.

Refsum disease (RD) [MIM:266500]: A rare autosomal recessive peroxisomal disorder characterized by the accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Cardinal clinical features are retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Half of all patients exhibit generalized, mild to moderate ichthyosis resembling ichthyosis vulgaris. Less constant features are nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac impairment. {ECO:0000269|PubMed:10709665, ECO:0000269|PubMed:10767344, ECO:0000269|PubMed:14974078, ECO:0000269|PubMed:9326939, ECO:0000269|PubMed:9326940}. The disease is caused by variants affecting the gene represented in this entry.

DB00159

NA

NA

3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein; Lipid-binding; Membrane; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

A

28319.1

272

0.11

27.3

9.07

6.85

-7.31

benC

Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)

NA

ACIAD1438

Bacterial ring-hydroxylating dioxygenase ferredoxin reductase family

Oxidoreductase

2 iron, 2 sulfur cluster binding.Electron carrier activity.Ferredoxin-NAD+ reductase activity.Metal ion binding.

Adenine phosphoribosyltransferase deficiency (APRTD) [MIM:614723]: An enzymatic deficiency that can lead to urolithiasis and renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones. {ECO:0000269|PubMed:11243733, ECO:0000269|PubMed:1353080, ECO:0000269|PubMed:15571218, ECO:0000269|PubMed:1746557, ECO:0000269|PubMed:21635362, ECO:0000269|PubMed:3343350, ECO:0000269|PubMed:3680503, ECO:0000269|PubMed:7915931}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

1.18.1.3

2Fe-2S; 3D-structure; Aromatic hydrocarbons catabolism; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; NAD; Oxidoreductase

A,B

37496.7

337

0.1

47.02

4.75

-18.87

-7.31

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

-7.32

AGXT

Homo sapiens (Human)

NA

AGT1;SPAT

Class-V pyridoxal-phosphate-dependent aminotransferase family

Transferase

Alanine-glyoxylate transaminase activity.Amino acid binding.Identical protein binding.Protein homodimerization activity.Protein self-association.Pyridoxal phosphate binding.Receptor binding.Serine-pyruvate transaminase activity.Transaminase activity.

Hyperoxaluria primary 1 (HP1) [MIM:259900]: An inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and progressive tissue accumulation of insoluble calcium oxalate. Affected individuals are at risk for nephrolithiasis, nephrocalcinosis and early onset end-stage renal disease. {ECO:0000269|PubMed:10394939, ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:10541294, ECO:0000269|PubMed:10862087, ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12559847, ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1301173, ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:15253729, ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:15963748, ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:1703535, ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:2039493, ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:24934730, ECO:0000269|PubMed:26149463, ECO:0000269|PubMed:8101040, ECO:0000269|PubMed:9192270, ECO:0000269|PubMed:9604803}. The disease is caused by variants affecting the gene represented in this entry.

DB08060; DB00160; DB02079; DB00145; DB04083; DB00114; DB00133

Q5BKX5-3; P21549; P0C7T5; Q9NR55; Q9H5F2; Q9UKJ5; A8MQ03; O43281-2; A1KXE4-2; Q5TD97; P49356; P53539; P49639; Q15323; O76011; O76014; Q6A162; Q07627; P60328; Q9BYR8; Q3LI67; Q8IUC2; Q9BYQ4; O60711; Q99750; Q5VZ52; P0DPK4; O43482; P50542-1; O15496; Q6ZR37; Q9NQX0; Q8HWS3; Q5W111-2; Q8WVR3; Q6DKK2

2.6.1.44; 2.6.1.51

3D-structure; Acetylation; Aminotransferase; Disease variant; Peroxisome; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A,B

84537

771

0.07

36.81

8.42

6.81

-7.31

BPHL

Homo sapiens (Human)

VACVase; MCNAA; DJ40E16.6.1; Breast epithelial mucin-associated antigen; Bph-rp; Biphenyl hydrolase-like protein (Serine hydrolase) (Breast epithelial mucin-associated antigen, MCNAA, Bph-rp), variant

AB hydrolase superfamily, Lipase family

Carboxylic ester hydrolase

Serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. Activates valacyclovir to acyclovir. May play a role in detoxification processes. It is a specific alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring aprimary alcohol.

Lecithin-cholesterol acyltransferase deficiency (LCATD) [MIM:245900]: A disorder of lipoprotein metabolism characterized by inadequate esterification of plasmatic cholesterol. Two clinical forms are recognized: complete LCAT deficiency and fish-eye disease. LCATD is generally referred to the complete form which is associated with absence of both alpha and beta LCAT activities resulting in esterification anomalies involving both HDL (alpha-LCAT activity) and LDL (beta-LCAT activity). It causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure. {ECO:0000269|PubMed:11423760, ECO:0000269|PubMed:12957688, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:16051254, ECO:0000269|PubMed:16216249, ECO:0000269|PubMed:1681161, ECO:0000269|PubMed:1859405, ECO:0000269|PubMed:2370048, ECO:0000269|PubMed:7607641, ECO:0000269|PubMed:7711728, ECO:0000269|PubMed:8318557, ECO:0000269|PubMed:8432868, ECO:0000269|PubMed:8807342, ECO:0000269|PubMed:9007616, ECO:0000269|PubMed:9741700}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fish-eye disease (FED) [MIM:136120]: A disorder of lipoprotein metabolism due to partial lecithin-cholesterol acyltransferase deficiency that affects only alpha-LCAT activity. FED is characterized by low plasma HDL and corneal opacities due to accumulation of cholesterol deposits in the cornea ('fish-eye'). {ECO:0000269|PubMed:1516702, ECO:0000269|PubMed:1571050, ECO:0000269|PubMed:15994445, ECO:0000269|PubMed:1737840, ECO:0000269|PubMed:21901787, ECO:0000269|PubMed:8620346, ECO:0000269|PubMed:9261271}. The disease is caused by variants affecting the gene represented in this entry.

DB03380

P62508-3

EC 3.1.-.-

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Hydrolase; Proteomics identification; Reference proteome; Signal

A

28823.7

254

0.11

25.18

8.31

2.59

-7.32

TK1

Homo sapiens (Human)

Thymidine kinase, cytosolic

Thymidine kinase family

Kinase

cytosol, identical protein binding, thymidine kinase activity, zinc ion binding, DNA metabolic process, nucleobase-containing compound metabolic process, protein homotetramerization, pyrimidine nucleoside salvage, thymidine metabolic process

Seizures, benign familial infantile, 3 (BFIS3) [MIM:607745]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:11371648, ECO:0000269|PubMed:12243921, ECO:0000269|PubMed:15048894, ECO:0000269|PubMed:16417554, ECO:0000269|PubMed:17021166, ECO:0000269|PubMed:17386050, ECO:0000269|PubMed:18479388, ECO:0000269|PubMed:20371507, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:23758435, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 11 (DEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. {ECO:0000269|PubMed:19783390, ECO:0000269|PubMed:19786696, ECO:0000269|PubMed:20956790, ECO:0000269|PubMed:22677033, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23195492, ECO:0000269|PubMed:23550958, ECO:0000269|PubMed:23662938, ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:23935176, ECO:0000269|PubMed:23988467, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:24579881, ECO:0000269|PubMed:24659627, ECO:0000269|PubMed:24710820, ECO:0000269|PubMed:25457084, ECO:0000269|PubMed:25459969, ECO:0000269|PubMed:25772804, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26291284, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:29625812, ECO:0000269|PubMed:29844171, ECO:0000269|PubMed:30144217, ECO:0000269|PubMed:30415926}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy. {ECO:0000269|PubMed:29635106}.; DISEASE: Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD. {ECO:0000269|PubMed:28256214}.; DISEASE: Episodic ataxia 9 (EA9) [MIM:618924]: An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development. {ECO:0000269|PubMed:26645390, ECO:0000269|PubMed:27159988, ECO:0000269|PubMed:27328862, ECO:0000269|PubMed:28065826}. The disease is caused by variants affecting the gene represented in this entry.

DB01692; DB04485; DB02452; DB00432; DB00495

P05067; A0A087WZT3; Q92993; Q1RN33; P04183

EC 2.7.1.21

3D-structure; Acetylation; ATP-binding; Cytoplasm; DNA synthesis; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Ubl conjugation; Zinc

A

19373.5

174

0.09

36.21

8.63

3.88

-7.31

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

-7.32

ARF1

Homo sapiens (Human)

PVNH8

Small GTPase superfamily, Arf family

Small GTPase

Modulates vesicle budding and uncoating within the Golgi complex. Deactivation induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, suggesting a crucial role in protein trafficking. In its GTP-bound form, its triggers the association with coat proteins with the Golgi membrane. The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles. The GTP-bound form interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3 complex activity; the function is linked to AMPA receptor (AMPAR) trafficking, regulation of synaptic plasicity of excitatory synapses and spine shrinkage during long-term depression (LTD). GTP-binding protein involved in protein trafficking among different compartments.

Periventricular nodular heterotopia 8 (PVNH8) [MIM:618185]: A form of periventricular nodular heterotopia, a disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches. PVNH8 is an autosomal dominant disease characterized by developmental disabilities, speech delay, seizures and attention deficit-hyperactivity disorder. {ECO:0000269|PubMed:28868155}. The disease is caused by variants affecting the gene represented in this entry.

DB02774; DB07348; DB09093; DB09462; DB04121; DB04315; DB04137; DB08231

P53367; P53365; Q99418; P46940; O60271

NA

3D-structure; Acetylation; Direct protein sequencing; Disease variant; ER-Golgi transport; Golgi apparatus; GTP-binding; Hydrolase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Protein transport; Proteomics identification; Reference proteome; Synapse; Synaptosome; Transport

A,B

41112.6

360

0.09

28.3

6.38

-1.68

-7.31

Bact metC

Escherichia coli (strain K12)

Cysteine-S-conjugate beta-lyase MetC; Cysteine lyase MetC; Cysteine desulfhydrase MetC; Cystathionine beta-lyase MetC; CL; CBL; Beta-cystathionase MetC; Bacterial CD

Trans-sulfuration enzymes family

Carbon-sulfur lyases

Primarily catalyzes the cleavage of cystathionine to homocysteine, pyruvate and ammonia during methionine biosynthesis. Also exhibits cysteine desulfhydrase activity, producing sulfide from cysteine. In addition, under certain growth conditions, exhibits significant alanine racemase coactivity.

Coronary artery disease, autosomal dominant, 2 (ADCAD2) [MIM:610947]: A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. {ECO:0000269|PubMed:17332414, ECO:0000269|PubMed:23703864}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Tooth agenesis, selective, 7 (STHAG7) [MIM:616724]: An autosomal dominant form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). {ECO:0000269|PubMed:26387593}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 4.4.1.13

3D-structure; Amino-acid biosynthesis; Cytoplasm; Direct protein sequencing; Lyase; Methionine biosynthesis; Pyridoxal phosphate; Reference proteome

A

42756.3

391

0.08

27.11

6.01

-6.11

-7.31

Cory pafA

Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / BCRC 11384 / CCUG 27702 / LMG 3730 / NBRC 12168 / NCIMB 10025 / NRRL B-2784 / 534)

Pup-conjugating enzyme; Pup--protein ligase; Proteasome accessory factor A

Pup ligase/Pup deamidase family, Pup-conjugating enzyme subfamily

NA

Catalyzes the covalent attachment of the prokaryotic ubiquitin-like protein modifier Pup to the proteasomal substrate proteins, thereby targeting them for proteasomal degradation. This tagging system is termed pupylation. The ligation reaction involves the side-chain carboxylate of the C-terminal glutamate of Pup and the side-chain amino group of a substrate lysine.

Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:30988594, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. The disease is caused by variants affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.

NA

NA

NA

3D-structure; ATP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding; Reference proteome; Ubl conjugation pathway

A,B

110572

994

0.07

42.33

5.26

-34.19

-7.32

HRH1

Homo sapiens (Human)

HH1R; H1R

G-protein coupled receptor 1 family

GPCR rhodopsin

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.

Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. {ECO:0000269|PubMed:22226083, ECO:0000269|PubMed:24549054}. The disease is caused by variants affecting the gene represented in this entry.

DB01615; DB09488; DB06766; DB01246; DB00321; DB00543; DB08799; DB01238; DB14185; DB06216; DB00637; DB00719; DB00972; DB00245; DB00767; DB04890; DB06698; DB11591; DB09128; DB01237; DB00835; DB00354; DB09016; DB00748; DB06016; DB00341; DB08936; DB08800; DB01114; DB00477; DB01239; DB00568; DB00215; DB00283; DB04837; DB00363; DB01176; DB00434; DB01151; DB00967; DB00405; DB09555; DB00985; DB08801; DB01075; DB01146; DB09167; DB01142; DB00366; DB01084; DB05492; DB00751; DB01175; DB06678; DB00950; DB04841; DB00502; DB05381; DB05079; DB00557; DB04946; DB00458; DB08802; DB00920; DB00555; DB01106; DB06282; DB00455; DB09195; DB00408; DB00934; DB00737; DB06691; DB01071; DB00902; DB01403; DB06148; DB00370; DB00540; DB05080; DB06229; DB00334; DB00768; DB01173; DB01267; DB00715; DB08922; DB01619; DB01620; DB06153; DB00433; DB00420; DB01069; DB00777; DB01224; DB00912; DB00734; DB11614; DB05345; DB00342; DB04905; DB11235; DB00797; DB00656; DB00726; DB00792; DB00427; DB09185; DB00246; DB01624

NA

NA

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

R

32298.5

275

0.15

36.59

9.54

16.01

-7.31

PEBP1

Homo sapiens (Human)

Raf kinase inhibitor protein; RKIP; Prostatic-binding protein; PEBP-1; PEBP; PBP; Neuropolypeptide h3; Hippocampal cholinergic neurostimulating peptide; HCNPpp; HCNP

Phosphatidylethanolamine-binding protein family

Phosphatidylethanolamine-binding protein family

Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation.

Retinitis pigmentosa 49 (RP49) [MIM:613756]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:15570217, ECO:0000269|PubMed:7479749}. The disease is caused by variants affecting the gene represented in this entry.

DB09130; DB09568

P16050; Q9NRD5; P04049; Q15208; Q9NS68; Q9JLL3

NA

3D-structure; ATP-binding; Cytoplasm; Direct protein sequencing; Disulfide bond; Lipid-binding; Nucleotide-binding; Phosphoprotein; Protease inhibitor; Proteomics identification; Reference proteome; Serine protease inhibitor

A

20928.3

186

0.1

24.05

6.59

-0.98

-7.31

xylA

Arthrobacter sp. (strain NRRL B3728)

NA

NA

Xylose isomerase family

Isomerase(intramolecular oxidoreductase)

Metal ion binding.Xylose isomerase activity.

Bachmann-Bupp syndrome (BABS) [MIM:619075]: An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. {ECO:0000269|PubMed:30239107, ECO:0000269|PubMed:30475435}. The disease is caused by variants affecting the gene represented in this entry. BABS is due to truncating variants that lead to a gain of function. This phenomenon apparently results from truncation proximal to or involving the C-terminal region of ODC1 protein, distal enough to allow escape from nonsense-mediated decay. A gain of function is corroborated by elevated plasma levels of N-acetylputrescine, with otherwise normal polyamine levels, in affected individuals. {ECO:0000269|PubMed:30475435}.

DB02172; DB03206; DB11195

NA

5.3.1.5

3D-structure; Carbohydrate metabolism; Cytoplasm; Direct protein sequencing; Isomerase; Magnesium; Metal-binding; Xylose metabolism

A,B

35700.7

325

0.11

20.63

5.19

-14.16

-7.3