HIF1A

Homo sapiens (Human)

bHLHe78; Transcription factor HIF-1; PASD8; PAS domain-containing protein 8; Member of PAS protein 1; MOP1; Hypoxia-inducible transcription factor (HIF)-1; Hypoxia-inducible factor 1-alpha; Hypoxia-in

NA

NA

Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. Functions as a master transcriptional regulator of the adaptive response to hypoxia.

Essential hypertension (EHT) [MIM:145500]: A condition in which blood pressure is consistently higher than normal with no identifiable cause. {ECO:0000269|PubMed:12372404}. The disease may be caused by variants affecting the gene represented in this entry.

DB02342; DB01136; DB05959; DB08687; DB01275; DB06082; DB12255

P10275; P27540; P49407; Q9C0J9; O00257; Q92793; P35222; Q96CJ1; Q9GZT9; Q96KS0; Q9H6Z9; Q09472; P11474; P49327; P09467; Q8N461; P23771; Q9NWT6; Q9Y2N7-4; Q92831; Q13330; P46531; Q13438; Q8N2W9; P14618-1; P25789; Q9UHD8-1; P84022; P08047; O60224; P63165; O94888; P40818; P40337; P17861; Q99PV5; Q5RIX9; Q6S7F2; Q61539; Q8BIF2; P51450-2

NA

3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding; Glycoprotein; Host-virus interaction; Hydroxylation; Isopeptide bond; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation

C,D

26523.9

236

0.1

24.97

5.58

-4.83

-7.63

ACAD8

Homo sapiens (Human)

NA

IBD;ARC42

Acyl-CoA dehydrogenase family

Oxidoreductase

Acyl-CoA dehydrogenase activity.Flavin adenine dinucleotide binding.

Isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]: An autosomal recessive metabolic disorder characterized by plasma carnitine deficiency and elevated C4-acylcarnitine. Patients manifest variable clinical features including failure to thrive, seizures, anemia, muscular hypotonia and developmental delay. Some patients may be asymptomatic. {ECO:0000269|PubMed:12359132, ECO:0000269|PubMed:15505379, ECO:0000269|PubMed:16857760}. The disease is caused by variants affecting the gene represented in this entry.

DB03147; DB01675

Q8TAG5

1.3.8.5

3D-structure; Acetylation; Activator; Alternative splicing; Branched-chain amino acid catabolism; Direct protein sequencing; Disease variant; FAD; Flavoprotein; Mitochondrion; Oxidoreductase; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Transit peptide

A,B,C,D

41689.3

384

0.08

40.81

6.39

-2.06

-7.63

LCMT1

Homo sapiens (Human)

NA

CGI-68;LCMT

Methyltransferase superfamily, LCMT family

Transferase

Protein C-terminal carboxyl O-methyltransferase activity.Protein C-terminal leucine carboxyl O-methyltransferase activity.S-adenosylmethionine-dependent methyltransferase 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.

DB00149

P51116

2.1.1.233

3D-structure; Alternative splicing; Methyltransferase; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A,B,C,D,E,F,G,H

35803

310

0.08

42.77

6.13

-3.58

-7.62

Malaria DHOdehase

Plasmodium falciparum (isolate 3D7)

PFF0160c; Mitochondrially bound dihydroorotate-ubiqui oxidoreductase; Dihydroorotate oxidase of Plasmodium falciparum; Dihydroorotate dehydrogenase of Plasmodium falciparum; DHOdehase of Plasmodium fa

Dihydroorotate dehydrogenase family, Type 2 subfamily

CH-CH donor oxidoreductase

Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.

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

DB01117

NA

EC 1.3.5.2

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

A

41846.8

371

0.1

37.25

8.21

3.13

-7.62

Pseudo LasR

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

Autoinducer-regulated transcriptional regulatory protein family

NA

Transcriptional activator of elastase structural gene (LasB). Binds to the PAI autoinducer.

Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400]: An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. {ECO:0000269|PubMed:8364549}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781]: An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:12655557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Kowarski syndrome (KWKS) [MIM:262650]: A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. {ECO:0000269|PubMed:17519310, ECO:0000269|PubMed:8552145, ECO:0000269|PubMed:9276733}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100]: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:11502836, ECO:0000269|PubMed:9152628}. The disease is caused by variants affecting the gene represented in this entry.

DB08324

NA

NA

3D-structure; Activator; DNA-binding; Quorum sensing; Reference proteome; Transcription; Transcription regulation

A

18305.5

163

0.12

46.52

5.19

-6.78

-7.62

TDO2

Homo sapiens (Human)

Tryptophanase; Tryptophan pyrrolase; Tryptophan oxygenase; Tryptamin 2,3-dioxygenase; TRPO; TO

Tryptophan 2,3-dioxygenase family

Oxygenase

Catalyzes the oxidative cleavage of the indole moiety. Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine.

Hypertryptophanemia (HYPTRP) [MIM:600627]: An autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia. {ECO:0000269|PubMed:28285122}. The disease is caused by variants affecting the gene represented in this entry.

DB00779; DB00500; DB00150

O43865; O95671; P27797; P12830; P36957; O60762; P06730; Q8TBB1; Q9H8S9; Q70IA8; Q8TDX7; Q9NPG2; Q9HAN9; P20393; Q9NRD5; Q8IYS1; O00560; Q9H190; P48775; Q68DK2-5

EC 1.13.11.11

3D-structure; Dioxygenase; Disease variant; Heme; Iron; Metal-binding; Oxidoreductase; Proteomics identification; Reference proteome; Tryptophan catabolism

A

42122.8

353

0.11

45.07

7.06

0.23

-7.62

H3F3A

Homo sapiens (Human)

PP781; Histone H3.3; H3F3; H3.3B; H3.3A

Histone H3 family

NA

Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Glioma (GLM) [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:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539269}. The gene represented in this entry is involved in disease pathogenesis. H3F3A mutations affecting residues involved in post-translational modifications of histone H3.3 are recurrent in malignant, aggressive gliomas including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286061, PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histones methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23539183, PubMed:23539269, PubMed:23603901). {ECO:0000269|PubMed:22286061, ECO:0000269|PubMed:22286216, ECO:0000269|PubMed:23539183, ECO:0000269|PubMed:23539269, ECO:0000269|PubMed:23603901}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 1 (BRYLIB1) [MIM:619720]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB1 is caused by variants in H3-3A. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: Bryant-Li-Bhoj neurodevelopmental syndrome 2 (BRYLIB2) [MIM:619721]: An autosomal dominant disorder predominantly characterized by global developmental delay, impaired intellectual development, poor or absent speech, and delayed motor milestones. Clinical manifestations are highly variable, including abnormal head shape, dysmorphic facial features, oculomotor abnormalities, feeding problems, and non-specific brain imaging abnormalities. Additional features may include hearing loss, seizures, short stature, and mild skeletal defects. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}. The disease is caused by variants affecting the gene represented in this entry. BRYLIB2 is caused by variants in H3-3B. {ECO:0000269|PubMed:33268356, ECO:0000269|PubMed:34876591}.; DISEASE: H3F3A and H3F3B mutations affecting residues involved in post-translational modifications of histone H3.3 are implicated in the pathogenesis of some bone and cartilage neoplasms. Mutations have been found with high prevalence in chondroblastoma and giant cell tumors of bone, and with low frequency in osteosarcoma, conventional chondrosarcoma and clear cell chondrosarcoma. Chondroblastoma samples frequently carry a H3F3B mutation affecting residue Lys-37 (H3K36), although H3F3A is mutated in some cases. Most giant cell tumors of bone harbor H3F3A mutations affecting residue Gly-35 (H3G34). {ECO:0000269|PubMed:24162739}.

NA

Q9NVP2; P45973; Q13111; Q9UER7; Q9UER7-1; Q9Y6K1; P62805; P49321-2; Q8IZL8; Q5VWG9; Q9VK33; Q8R5C8

NA

3D-structure; Acetylation; ADP-ribosylation; Chromosome; Citrullination; Direct protein sequencing; Disease variant; DNA-binding; Hydroxylation; Intellectual disability; Lipoprotein; Methylation; Nucleosome core; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation

A,C

86148.9

766

0.1

37.57

8.25

7.16

-7.63

SLC14A1

Homo sapiens (Human)

Urea transporter, erythrocyte; UTE; UT1; Solute carrier family 14 member 1; RACH1; JK; HUT11

Urea transporter family

Urea transporter family

Urea channel that facilitates transmembrane urea transport down a concentration gradient. A constriction of the transmembrane channel functions as selectivity filter through which urea is expected to pass in dehydrated form. The rate of urea conduction is increased by hypotonic stress. Plays an important role in the kidney medulla collecting ducts, where it allows rapid equilibration between the lumen of the collecting ducts and the interstitium, and thereby prevents water loss driven by the high concentration of urea in the urine. Facilitates urea transport across erythrocyte membranes. May also play a role in transmembrane water transport, possibly by indirect means.

Immunodeficiency 12 (IMD12) [MIM:615468]: A primary immunodeficiency characterized by onset in infancy of recurrent bacterial and candidal infections resulting in bronchiectasis and growth delay. Manifestations include mastoiditis, aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, duodenitis, and meningitis. Levels of absolute lymphocytes and serum immunoglobulins are normal, but specific antibody titers are low despite immunization, and T-cells show impaired proliferative responses to mitogens. {ECO:0000269|PubMed:23727036}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: A chromosomal aberration involving MALT1 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with BIRC2. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma. {ECO:0000269|PubMed:10339464, ECO:0000269|PubMed:10523859, ECO:0000269|PubMed:10702396, ECO:0000269|PubMed:11090634}.

DB01005; DB03904

Q8WVV5; Q9Y3D6; Q8WWP7; P30301; Q5QGT7; Q6UX34; P0DN84; Q9C0I4; Q5BJF2

NA

3D-structure; Alternative splicing; Blood group antigen; Cell membrane; Glycoprotein; Membrane; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

A

38862.8

356

0.12

40.98

7.67

0.95

-7.62

KIT

Homo sapiens (Human)

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; p145 c-kit; Proto-oncogene tyrosine-protein kinase Kit; Proto-oncogene c-Kit; Piebald trait protein; PBT; Mast/stem cell growth factor re

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

Kinase

In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis.

Piebald trait (PBT) [MIM:172800]: Autosomal dominant genetic developmental abnormality of pigmentation characterized by congenital patches of white skin and hair that lack melanocytes. {ECO:0000269|PubMed:11074500, ECO:0000269|PubMed:1370874, ECO:0000269|PubMed:1376329, ECO:0000269|PubMed:1717985, ECO:0000269|PubMed:7687267, ECO:0000269|PubMed:8680409, ECO:0000269|PubMed:9450866, ECO:0000269|PubMed:9699740}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:11505412, ECO:0000269|PubMed:15824741, ECO:0000269|PubMed:9438854, ECO:0000269|PubMed:9697690}. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The gene represented in this entry is involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of KIT are detected in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the kinase domain can result in a constitutively activated kinase.; DISEASE: Mastocytosis, cutaneous (MASTC) [MIM:154800]: A form of mastocytosis, a heterogeneous group of disorders associated with abnormal proliferation and accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. MASTC is an autosomal dominant form characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed Darier sign. {ECO:0000269|PubMed:15173254, ECO:0000269|PubMed:19865100, ECO:0000269|PubMed:21689725, ECO:0000269|PubMed:24289326, ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mastocytosis, systemic (MASTSYS) [MIM:154800]: A severe form of mastocytosis characterized by abnormal proliferation and accumulation of mast cells in several organs, resulting in a systemic disease that may affect bone, gastrointestinal tract, lymphatics, spleen, and liver. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. It can also lead to mast cell leukemia, which carries a high risk of mortality. {ECO:0000269|PubMed:9990072}. The disease is caused by variants affecting the gene represented in this entry.

DB12742; DB09103; DB15233; DB01254; DB12147; DB12010; DB00619; DB09078; DB06080; DB06595; DB04868; DB05913; DB06589; DB12978; DB01962; DB08901; DB08896; DB14840; DB00398; DB01268; DB11800; DB05146

P00519; P42684; O75815; P51451; Q8WV28; P46108; P07332; P09769; O75791; P62993; Q14451; P08631; Q96JZ2; P21583; P06239; P07948; P16333; O43639; P27986; O00459; Q92569; P19174; P16885; Q13882; Q06124; Q92729; P20936; Q9UQQ2; O14796; Q9NP31; Q8N5H7; P78314; Q15464; P29353; P98077; Q92529; Q9H6Q3; O14508; O14543; O14544; P12931; Q9ULZ2; Q9HBL0; Q63HR2; Q68CZ2; P42681; P07947; P43403; Q8VBX6; P35235

EC 2.7.10.1

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

A

33575.6

297

0.11

45.37

8.37

3.24

-7.61

pobA

Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

NA

PA0247

Aromatic-ring hydroxylase family

Hydrolase

4-hydroxybenzoate 3-monooxygenase activity.FAD binding.Flavin adenine dinucleotide binding.

Immunodeficiency, common variable, 12, with autoimmunity (CVID12) [MIM:616576]: A primary immunodeficiency characterized by hypogammaglobulinemia and recurrent bacterial infections. About half of patients develop autoimmune features, including cytopenia, as well as generalized inflammation and lymphoproliferation manifest as lymphadenopathy or hepatosplenomegaly. {ECO:0000269|PubMed:26279205}. The disease is caused by variants affecting the gene represented in this entry.

DB02839; DB04242; DB03482; DB02362; DB03147

NA

1.14.13.2

3D-structure; Aromatic hydrocarbons catabolism; FAD; Flavoprotein; Monooxygenase; NADP; Oxidoreductase; Reference proteome

A

44295

394

0.09

37.66

6.2

-3.67

-7.61

CDK8

Homo sapiens (Human)

Protein kinase K35; Mediator of RNA polymerase II transcription subunit CDK8; Mediator complex subunit CDK8; Cell division protein kinase 8

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

Kinase

Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes.

Intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA) [MIM:618748]: An autosomal dominant neurodevelopmental disorder with onset in infancy. IDDHBA is characterized by hypotonia, global developmental delay, learning disability, and behavioral abnormalities, such as autistic features and attention deficit-hyperactivity disorder. Additional variable features may include non-specific facial dysmorphism, congenital heart defects, ocular anomalies, and poor feeding. {ECO:0000269|PubMed:30905399}. The disease is caused by variants affecting the gene represented in this entry.

DB03496

P24863; Q01094; P02489; Q14204; Q92876

EC 2.7.11.22

3D-structure; Activator; Alternative splicing; ATP-binding; Autism spectrum disorder; Disease variant; Intellectual disability; Kinase; Nucleotide-binding; Nucleus; Proteomics identification; Reference proteome; Repressor; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase

A

37655.2

321

0.11

37.04

8.56

5.13

-7.61

Malaria DXR

Plasmodium falciparum (isolate HB3)

IspC; DXR; DXP reductoisomerase; DOXP reductoisomerase; 2-C-Methyl-d-erythritol 4-phosphate synthase; 1-deoxyxylulose-5-phosphate reductoisomerase

DXR family

Short-chain dehydrogenases reductase

Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).

Ichthyosis, congenital, autosomal recessive 11 (ARCI11) [MIM:602400]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:17273967, ECO:0000269|PubMed:18843291}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.1.1.267

3D-structure; Apicoplast; Isoprene biosynthesis; Magnesium; Manganese; Metal-binding; NADP; Oxidoreductase; Plastid; Transit peptide

A

46644.4

410

0.09

36.77

6.95

-0.14

-7.61

MDM4

Homo sapiens (Human)

Protein Mdmx; Mdm2-like p53-binding protein; Double minute 4 protein

MDM2/MDM4 family

MDM2/MDM4 family

Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.

Bone marrow failure syndrome 6 (BMFS6) [MIM:618849]: 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. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer. {ECO:0000269|PubMed:32300648}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NX04; P10415; Q7Z479; O95971; P48729; Q00987; Q13064; P41227; P06400; Q9Y4L5; P23297; P29034; P33763; P04271; P31947; P04637; P62837; Q93009; O14972; P61964; P62258; P61981; P63104; Q9BRR0; A0A0S2Z6X0; Q3YBA8; P03255-2

NA

3D-structure; Alternative splicing; Disease variant; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Zinc; Zinc-finger

A,B

19722

173

0.08

50.78

8.48

2.27

-7.62

HBV C

Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979) (HBV-D)

Core antigen; Core protein; HBcAg; p21.5

Orthohepadnavirus core antigen family

NA

Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with an icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions.

Oocyte/zygote/embryo maturation arrest 14 (OZEMA14) [MIM:620276]: An autosomal recessive female infertility disorder characterized by oocyte maturation arrest, fertilization failure, and/or early embryonic arrest. {ECO:0000269|PubMed:32666501, ECO:0000269|PubMed:33683667, ECO:0000269|PubMed:33898437, ECO:0000269|PubMed:34218387}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

NA

3D-structure; Alternative initiation; Capsid protein; Cytoplasmic inwards viral transport; DNA-binding; Host cytoplasm; Host-virus interaction; Microtubular inwards viral transport; Phosphoprotein; Reference proteome; Repeat; RNA-binding; T=4 icosahedral capsid protein; Viral penetration into host nucleus; Virion; Virus entry into host cell

A,B

32388.9

286

0.12

42.05

5.06

-11.81

-7.61

MMP10

Homo sapiens (Human)

Transin-2; Stromelysin-2; STMY2; SL-2

Peptidase M10A family

Peptidase

Activates procollagenase. Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V.

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.

DB00786; DB08271

NA

EC 3.4.24.22

3D-structure; Calcium; Collagen degradation; Disulfide bond; Extracellular matrix; Hydrolase; Metal-binding; Metalloprotease; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen

A,B,C

52822

471

0.12

21.13

4.83

-35.32

-7.59

SULT1E1

Homo sapiens (Human)

NA

STE

Sulfotransferase 1 family

Transferase

Aryl sulfotransferase activity.Estrone sulfotransferase activity.Flavonol 3-sulfotransferase activity.Steroid binding.Steroid sulfotransferase activity.Sulfotransferase activity.

Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN) [MIM:137200]: An autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves. {ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:22961002, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:31088288}. The disease is caused by variants affecting the gene represented in this entry.

DB02902; DB03346; DB01812; DB00714; DB14635; DB01176; DB00977; DB09288; DB00675; DB09100

O76083; O76083-2

2.8.2.4

3D-structure; Cytoplasm; Lipid metabolism; Lipid-binding; Proteomics identification; Reference proteome; Steroid-binding; Transferase

A,B

34022.7

285

0.15

32.76

6.33

-2.75

-7.6

GAMT

Homo sapiens (Human)

NA

NA

Class I-like SAM-binding methyltransferase superfamily, RMT2 methyltransferase family

Transferase

Guanidinoacetate N-methyltransferase activity.Methyltransferase activity.

Cerebral creatine deficiency syndrome 2 (CCDS2) [MIM:612736]: An autosomal recessive disorder characterized by developmental delay and regression, intellectual disability, severe disturbance of expressive and cognitive speech, intractable seizures, movement disturbances, severe depletion of creatine and phosphocreatine in the brain, and accumulation of guanidinoacetic acid in brain and body fluids. {ECO:0000269|PubMed:12468279, ECO:0000269|PubMed:15108290, ECO:0000269|PubMed:15651030, ECO:0000269|PubMed:16293431, ECO:0000269|PubMed:16855203, ECO:0000269|PubMed:17101918, ECO:0000269|PubMed:17466557, ECO:0000269|PubMed:19388150, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:24415674, ECO:0000269|PubMed:8651275}. The disease is caused by variants affecting the gene represented in this entry.

DB00148; DB02751; DB00536; DB13191; DB01752

O95363; Q969Q5; Q9HCM9-2

2.1.1.2

3D-structure; Acetylation; Alternative splicing; Disease variant; Methyltransferase; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A,B,C,D

24656

219

0.11

46.5

5.91

-4.34

-7.6

mmaA2

Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

NA

Rv0644c;mma2

CFA/CMAS family

Transferase

Cyclopropane-fatty-acyl-phospholipid synthase activity.Methyltransferase activity.

Oocyte/zygote/embryo maturation arrest 16 (OZEMA16) [MIM:617234]: A rare cause of female primary infertility. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27545678}. The disease is caused by variants affecting the gene represented in this entry.

DB01718; DB01752

NA

2.1.1.79

3D-structure; Acetylation; Lipid biosynthesis; Lipid metabolism; Methyltransferase; Reference proteome; S-adenosyl-L-methionine; Transferase

A

32493.6

285

0.1

43.61

5.53

-10.17

-7.6

KMT5C

Homo sapiens (Human)

Lysine N-methyltransferase 5C; Lysine-specific methyltransferase 5C; Suppressor of variegation 4-20 homolog 2; Su(var)4-20 homolog 2; Suv4-20h2; [histone H4]-N-methyl-L-lysine20 N-methyltransferase KM

Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, Suvar4-20 subfamily

NA

Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity. In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4. May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).

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

NA

Q13185

EC 2.1.1.361

3D-structure; Alternative splicing; Chromatin regulator; Chromosome; Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase; Zinc

A

27285.8

240

0.1

42.74

8.32

3.24

-7.6

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

-7.58