CRBN

Homo sapiens (Human)

Protein cereblon

CRBN family

NA

Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. May play a role in memory and learning by regulating the assembly and neuronal surface expression of large-conductance calcium-activated potassium channels in brain regions involved in memory and learning via its interaction with KCNT1. Binding of pomalidomide and other thalidomide-related drugs changes the substrate specificity of the human protein, leading to decreased degradation of MEIS2 and other target proteins and increased degradation of MYC, IRF4, IKZF1 and IKZF3.

Intellectual developmental disorder, autosomal recessive 2 (MRT2) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. {ECO:0000269|PubMed:15557513, ECO:0000269|PubMed:28143899}. The disease is caused by variants affecting the gene represented in this entry.

DB00480; DB08910; DB01041

Q96A83-2; P48729; Q16531; O14901; Q8IVT2; Q9P286; A0A6Q8PF08; Q93062; Q16531; Q13422-7

NA

3D-structure; Alternative splicing; Cytoplasm; Disease variant; Intellectual disability; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc

B,E

38245.7

337

0.08

40.62

5.7

-6.53

-7.15

KDM4C

Homo sapiens (Human)

KIAA0780; Jumonji domain-containing protein 2C; JmjC domain-containing histone demethylation protein 3C; JMJD2C; JHDM3C; Gene amplified in squamous cell carcinoma 1 protein; GASC1; GASC-1 protein

JHDM3 histone demethylase family

Paired donor oxygen oxidoreductase

Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code.

Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269|PubMed:20054297, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}. The disease may be caused by variants affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682). {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.; DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: An autosomal dominant syndrome with a variable phenotype. Clinical features include macrocephaly, distinctive facial appearance, postnatal overgrowth, various degrees of learning difficulties, autism spectrum disorder, and intellectual disability. {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24852293, ECO:0000269|PubMed:26084711, ECO:0000269|PubMed:27317772}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24662245}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; 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. {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Intellectual developmental disorder, autosomal dominant 70 (MRD70) [MIM:620157]: An autosomal dominant disorder characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rabin-Pappas syndrome (RAPAS) [MIM:620155]: An autosomal dominant neurodevelopmental disorder characterized by severely impaired global development, intellectual disability, microcephaly, facial dysmorphism, and variable congenital anomalies affecting the skeletal, genitourinary, cardiac, and other organ systems. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.14.11.-

3D-structure; Alternative splicing; Chromatin regulator; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Zinc; Zinc-finger

A

39355.6

338

0.14

38.34

8.04

2.41

-7.14

CUL4A/CUL4B-DDB1-CRBN

Homo sapiens (Human)

NA

Cullin family

NA

NA

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

NA

P54253; Q86VP6; Q16531; Q92466; P08238; O94888; P55072

NA

3D-structure; Alternative splicing; Biological rhythms; DNA damage; DNA repair; Host-virus interaction; Isopeptide bond; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Ubl conjugation pathway

B

42669.7

368

0.1

44.94

8.72

6.58

-7.09

IKZF2

Homo sapiens (Human)

Ikaros family zinc finger protein 2

Ikaros C2H2-type zinc-finger protein family

NA

Associates with Ikaros at centromeric heterochromatin.

Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta (DEE25) [MIM:615905]: An autosomal recessive disease characterized by subclinical seizures appearing in the first days of life, evolving to severe epileptic disease. Affected individuals have profound or severe delayed development with lack of speech, and most patients do not acquire the ability to sit. Additional variable features include axial hypotonia, peripheral hypertonia, and abnormal involuntary movements such as dystonia and choreoathetosis. Dental abnormalities, including delayed eruption, hypodontia, tooth hypoplasia, yellow discoloration, thin enamel, and enamel chipping are observed in most patients. {ECO:0000269|PubMed:24995870, ECO:0000269|PubMed:26384929, ECO:0000269|PubMed:30054523}. The disease is caused by variants affecting the gene represented in this entry.

NA

P29972; P56545; P56545-3; Q17RB8; P09022; Q8N8B7-2

NA

3D-structure; Acetylation; Activator; Alternative splicing; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

B,C

47006.6

410

0.09

44.28

7.23

0.69

-7.09

ACADM

Homo sapiens (Human)

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Acyl-CoA dehydrogenase activity.Flavin adenine dinucleotide binding.Identical protein binding.Medium-chain-acyl-CoA dehydrogenase activity.

Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. The disease is caused by variants affecting the gene represented in this entry.

DB03415; DB03147; DB02910

PRO_0000000502 [P11310]

1.3.8.7

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; Disease variant; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; Mitochondrion; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transit peptide

A,B,C,D

85080.3

773

0.09

30.55

5.71

-7.7

-7.02

CHRNA2

Homo sapiens (Human)

NA

NA

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-2/CHRNA2 sub-subfamily

NA

After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane."

Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353]: An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. {ECO:0000269|PubMed:16826524}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353]: 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. BFIS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:25847220}. The disease may be caused by variants affecting the gene represented in this entry.

DB00732; DB00237; DB00411; DB00565; DB01245; DB00514; DB01135; DB07720; DB00898; DB00472; DB00483; DB08960; DB00657; DB01336; DB00416; DB01226; DB00184; DB01337; DB01338; DB00721; DB00728; DB05740; DB00202; DB01199; DB01339

NA

NA

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; Transport

A,B,C,D,E

120584

1031

0.14

32.21

5.62

-17.58

-7.03

AKR1B1

Homo sapiens (Human)

Aldehyde reductase; AKR1B1

Aldo/keto reductase family

Short-chain dehydrogenases reductase

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.

Glutamine deficiency, congenital (GLND) [MIM:610015]: An autosomal recessive disorder characterized by variable brain malformations, encephalopathy, severe developmental delay, seizures, and decreased glutamine levels in bodily fluids. Death in early infancy may occur. {ECO:0000269|PubMed:16267323, ECO:0000269|PubMed:26711351, ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 116 (DEE116) [MIM:620806]: A form of epileptic encephalopathy, a heterogeneous group of 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. DEE116 is autosomal dominant form characterized by severe developmental delay, seizures, and white matter abnormalities. {ECO:0000269|PubMed:38579670}. The disease is caused by variants affecting the gene represented in this entry. DEE116 is caused by variants that disrupt the canonical translation start codon in GLUL resulting in initiation of translation at Met-18 (PubMed:38579670). The resulting protein is enzymatically competent but insensitive to negative feedback regulation via glutamine-induced degradation. {ECO:0000269|PubMed:38579670}.

DB07028; DB07030; DB07450; DB02101; DB08449; DB08000; DB07139; DB07498; DB02007; DB02020; DB11859; DB02994; DB04272; DB07187; DB00694; DB00997; DB06246; DB01039; DB02021; DB16707; DB00143; DB02834; DB08084; DB01689; DB07063; DB06077; DB02518; DB00157; DB03461; DB05383; DB05533; DB05327; DB02712; DB00605; DB02383; DB02132; DB08772; DB07093; DB07999; DB08098

Q9BUY7

EC 1.1.1.300

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome

A

35447.6

313

0.09

36.41

7.1

0.26

-7.01

MET

Homo sapiens (Human)

Tyrosine-protein kinase Met; Scatter factor receptor; SF receptor; Met proto-oncogene tyrosine kinase; Hepatocyte growth factor receptor; HGF/SF receptor; HGF-SF receptor; HGF receptor; C-met; C-Met r

Protein kinase superfamily, Tyr protein kinase family

Kinase

Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

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

EC 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

35229.5

312

0.1

37.98

7.79

1.93

-7.01

cpo

Kitasatospora aureofaciens (Streptomyces aureofaciens)

NA

cpoT

AB hydrolase superfamily, Bacterial non-heme haloperoxidase / perhydrolase family

Haloperoxidase

Chloride peroxidase activity.

Hypervalinemia and hyperleucine-isoleucinemia (HVLI) [MIM:618850]: An autosomal recessive metabolic disorder characterized by highly elevated plasma concentrations of valine and leucine/isoleucine. Affected individuals suffer from headache and mild memory impairment. {ECO:0000269|PubMed:25653144}. The disease is caused by variants affecting the gene represented in this entry. A patient with hypervalinemia and hyperleucine-isoleucinemia was identified as compound heterozygote for Gln-170 (inherited from his father) and Lys-264 (inherited from his mother), both variants reduced the catalytic activity of the enzyme. After treatment with vitamin B6, a precursor of pyridoxal 5'-phosphate, a BCAT2 cofactor, the blood levels of branched chain amino acids, especially valine, were decreased and brain lesions were improved. {ECO:0000269|PubMed:25653144}.

DB03793

NA

1.11.1.-

3D-structure; Chloride; Oxidoreductase; Peroxidase

A,B

60428.4

554

0.13

31.26

4.65

-32.72

-6.99

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

-7

CHD1

Homo sapiens (Human)

NA

NA

SNF2/RAD54 helicase family

Dna binding protein / viral protein

ATP binding.ATP-dependent DNA helicase activity.DNA binding.Methylated histone binding.

Pilarowski-Bjornsson syndrome (PILBOS) [MIM:617682]: An autosomal dominant disorder characterized by developmental delay, speech apraxia, intellectual disability, autism, and facial dysmorphic features. Some patients may have seizures. {ECO:0000269|PubMed:28866611}. The disease is caused by variants affecting the gene represented in this entry.

NA

O60341-1; B2BUF1; P28799; O76024

3.6.4.12

3D-structure; Alternative splicing; ATP-binding; Chromatin regulator; Cytoplasm; Disease variant; DNA-binding; Helicase; Hydrolase; Intellectual disability; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Transcription; Transcription regulation

A

20969.1

180

0.12

46.35

5.88

-2.83

-7

SSTR4

Homo sapiens (Human)

SSTR4; SS4R

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.

Oocyte/zygote/embryo maturation arrest 21 (OZEMA21) [MIM:620610]: An autosomal dominant, female infertility disorder characterized by zygote development arrest due to failure of pronuclei fusion. {ECO:0000269|PubMed:33948904, ECO:0000269|PubMed:33953335}. The disease is caused by variants affecting the gene represented in this entry.

DB13985; DB09099

P35346

NA

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

R

29548.3

265

0.12

45.65

9.78

14.03

-6.99

DRD2

Homo sapiens (Human)

Dopamine receptor 2; D(2) dopamine receptor

G-protein coupled receptor 1 family

GPCR rhodopsin

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

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

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

Q9NRI5; P14416; Q01959

NA

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

B,C

24300.3

209

0.13

40.14

4.97

-7.83

-6.98

N/A

Plasmodium falciparum (isolate HB3)

NA

NA

Peptidase A1 family

Hydrolase

Aspartic-type endopeptidase activity.

Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]: Autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features. {ECO:0000269|PubMed:10832746, ECO:0000269|PubMed:11013134, ECO:0000269|PubMed:16317551}. The disease is caused by variants affecting the gene represented in this entry.

DB04378; DB04373; DB11638; DB01218; DB02505; DB03063

NA

3.4.23.39

3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond; Hydrolase; Membrane; Protease; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Vacuole; Zymogen

A

36923.5

329

0.13

44.31

4.67

-17.94

-6.98

PTGER4

Homo sapiens (Human)

Prostanoid EP4 receptor; Prostaglandin E2 receptor EP4 subtype; PTGER2; PGE2 receptor EP4 subtype; PGE receptor EP4 subtype

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.

MUC1/CA 15-3 is used as a serological clinical marker of breast cancer to monitor response to breast cancer treatment and disease recurrence (PubMed:20816948). Decreased levels over time may be indicative of a positive response to treatment. Conversely, increased levels may indicate disease progression. At an early stage disease, only 21% of patients exhibit high MUC1/CA 15-3 levels, that is why CA 15-3 is not a useful screening test. Most antibodies target the highly immunodominant core peptide domain of 20 amino acid (APDTRPAPGSTAPPAHGVTS) tandem repeats. Some antibodies recognize glycosylated epitopes. {ECO:0000269|PubMed:20816948}.; DISEASE: Tubulointerstitial kidney disease, autosomal dominant, 2 (ADTKD2) [MIM:174000]: A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance. {ECO:0000269|PubMed:23396133}. The disease is caused by variants affecting the gene represented in this entry.

DB00770; DB11113; DB00917; DB12836; DB09211; DB00929; DB16315; DB04297

NA

NA

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

A

31760.4

285

0.12

39.15

9.03

7.72

-6.99

ADA

Plasmodium vivax (strain Salvador I)

NA

PVX_111245

Metallo-dependent hydrolases superfamily, Adenosine and AMP deaminases family

NA

Catalyzes the hydrolytic deamination of adenosine to produce inosine (PubMed:19728741). Unlike mammalian adenosine deaminases, also catalyzes the deamination of 5'-methylthioadenosine (MTA), a by-product of polyamine biosynthesis, to produce 5'-methylthioinosine (MTI) (PubMed:19728741). Plays an essential role in the purine salvage pathway which allows the parasite to use host cell purines for the synthesis of nucleic acids (PubMed:19728741). {ECO:0000269|PubMed:19728741}."

NA

NA

NA

3.5.4.31; 3.5.4.4

3D-structure; Hydrolase; Metal-binding; Purine salvage; Reference proteome; Zinc

A

41950.8

364

0.11

27.19

5.49

-13.73

-6.98

DRD2

Homo sapiens (Human)

Dopamine receptor 2; D(2) dopamine receptor

G-protein coupled receptor 1 family

GPCR rhodopsin

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

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

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

Q9NRI5; P14416; Q01959

NA

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

B,C

24300.3

209

0.13

40.14

4.97

-7.83

-6.97

pgl

Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

NA

devB;TM_1154

Glucosamine/galactosamine-6-phosphate isomerase family, 6-phosphogluconolactonase subfamily

Hydrolase

6-phosphogluconolactonase activity.

A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. {ECO:0000269|PubMed:15938644}.; DISEASE: A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. {ECO:0000269|PubMed:12112524, ECO:0000269|PubMed:16161041}.; DISEASE: A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. {ECO:0000269|PubMed:12112524}.; DISEASE: Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. {ECO:0000269|PubMed:18724359, ECO:0000269|PubMed:18923523, ECO:0000269|PubMed:18923525, ECO:0000269|PubMed:21242967, ECO:0000269|PubMed:22932897}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth. {ECO:0000269|PubMed:15908427}.; DISEASE: A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion. {ECO:0000269|PubMed:22327622}.; DISEASE: A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation. {ECO:0000269|PubMed:17625570}.

DB04272; DB01942

NA

3.1.1.31

3D-structure; Hydrolase; Reference proteome

A

25064.5

218

0.11

31.92

7.04

0.05

-6.97

SCN9A

Homo sapiens (Human)

hNE-Na; Voltage-gated sodium channel subunit alpha Nav1.7; Sodium channel proteintype IX subunit alpha; Sodium channel proteintype 9 subunit alpha; Sodium channel protein type IX subunit alpha; Sodium

Sodium channel (TC 1.A.1.10) family, Nav1.7/SCN9A subfamily

Voltage-gated ion channel

Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain. Mediates the voltage-dependent sodium ion permeability of excitable membranes.

Primary erythermalgia (PERYTHM) [MIM:133020]: Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. {ECO:0000269|PubMed:14985375, ECO:0000269|PubMed:15385606, ECO:0000269|PubMed:15955112, ECO:0000269|PubMed:15958509, ECO:0000269|PubMed:16216943, ECO:0000269|PubMed:16392115, ECO:0000269|PubMed:16702558, ECO:0000269|PubMed:16988069, ECO:0000269|PubMed:18945915, ECO:0000269|PubMed:19369487, ECO:0000269|PubMed:24311784}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Indifference to pain, congenital, autosomal recessive (CIP) [MIM:243000]: A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. {ECO:0000269|PubMed:20635406}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Paroxysmal extreme pain disorder (PEXPD) [MIM:167400]: An autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing. {ECO:0000269|PubMed:17145499, ECO:0000269|PubMed:18945915, ECO:0000269|PubMed:25285947}. The disease is caused by variants affecting the gene represented in this entry.

DB09088; DB13746; DB05541; DB00564; DB01161; DB00907; DB13269; DB13961; DB06218; DB00555; DB00281; DB00776; DB11186; DB09345; DB01069; DB09342; DB00243; DB06201; DB09085; DB00273; DB00313; DB00909

NA

NA

3D-structure; Alternative splicing; Cell membrane; Cell projection; Disease variant; Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel

A

162402

1418

0.14

35.66

6.72

-1.33

-6.97

MIF

Homo sapiens (Human)

Phenylpyruvate tautomerase; MMIF; L-dopachrome tautomerase; L-dopachrome isomerase; Glycosylation-inhibiting factor; GLIF; GIF

MIF family

Intramolecular oxidoreductase

Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity. Pro-inflammatory cytokine.

Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:11508429}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB01880; DB07888; DB08334; DB08335; DB08333; DB07718; DB08765; DB02728

O43521-2; P00533; Q92743; P14174; Q96HA8

EC 5.3.2.1

3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Isomerase; Proteomics identification; Reference proteome; Secreted

A,C

24671.9

228

0.09

31.45

8.37

2.26

-6.97