HPD

Homo sapiens (Human)

NA

PPD

4HPPD family

Oxidoreductase

4-hydroxyphenylpyruvate dioxygenase activity.Metal ion binding.

Tyrosinemia 3 (TYRSN3) [MIM:276710]: An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, seizures and mild intellectual disability. {ECO:0000269|PubMed:10942115, ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hawkinsinuria (HWKS) [MIM:140350]: An inborn error of tyrosine metabolism characterized by failure to thrive, persistent metabolic acidosis, fine and sparse hair, and excretion of the unusual cyclic amino acid metabolite, hawkinsin, in the urine. {ECO:0000269|PubMed:11073718}. The disease is caused by variants affecting the gene represented in this entry.

DB02850; DB00348

NA

1.13.11.27

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Dioxygenase; Disease variant; Endoplasmic reticulum; Golgi apparatus; Intellectual disability; Iron; Membrane; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Tyrosine catabolism

A

43164.8

376

0.11

32.38

6.73

-1.04

-6.88

PTK6

Homo sapiens (Human)

Protein-tyrosine kinase 6; Breast tumor kinase; BRK

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

Kinase

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

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

DB12010; DB11800; DB05294; DB15035

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

EC 2.7.10.2

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

A

30240.6

264

0.09

46.88

6.95

-0.14

-6.89

CSAD

Homo sapiens (Human)

NA

CSD

Group II decarboxylase family

Lyase

Pyridoxal phosphate binding.Sulfinoalanine decarboxylase activity.

Myopathy with lactic acidosis and sideroblastic anemia 2 (MLASA2) [MIM:613561]: A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest sideroblastic anemia, progressive lethargy, muscle weakness, and exercise intolerance associated with persistent lactic acidemia. {ECO:0000269|PubMed:20598274, ECO:0000269|PubMed:22504945}. The disease is caused by variants affecting the gene represented in this entry.

DB00151; DB00114

NA

4.1.1.11; 4.1.1.29

3D-structure; Alternative splicing; Decarboxylase; Lyase; Proteomics identification; Pyridoxal phosphate; Reference proteome

A,B

107737

965

0.08

39.32

6.39

-5.38

-6.89

HNF4A

Homo sapiens (Human)

Transcription factor HNF-4; Transcription factor 14; TCF14; TCF-14; Nuclear receptor subfamily 2 group A member 1; NR2A1; HNF4; HNF-4-alpha

Nuclear hormone receptor family, NR2 subfamily

Nuclear hormone receptor

Activates the transcription of CYP2C38. Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells. Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes.

Maturity-onset diabetes of the young 1 (MODY1) [MIM:125850]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10389854, ECO:0000269|PubMed:17407387, ECO:0000269|PubMed:9243109, ECO:0000269|PubMed:9313765}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:9449683}. Disease susceptibility may be associated with variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4) [MIM:616026]: An autosomal dominant disease characterized by Fanconi syndrome associated with a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Fanconi syndrome is a proximal tubulopathy resulting in generalized aminoaciduria, low molecular weight proteinuria, glycosuria, hyperphosphaturia and hypouricemia. Some FRTS4 patients have nephrocalcinosis, renal impairment, hypercalciuria with relative hypocalcemia, and hypermagnesemia. {ECO:0000269|PubMed:22802087, ECO:0000269|PubMed:24285859}. The disease is caused by variants affecting the gene represented in this entry.

DB05447; DB03017; DB08231

Q99967; A8MYZ6; P04150; Q9UBK2; Q92786; P23246; Q12772; P04637; P11532; O14602; O43688

NA

3D-structure; Acetylation; Activator; Alternative promoter usage; Alternative splicing; Biological rhythms; Diabetes mellitus; Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

B

23446.1

205

0.08

39.17

5.05

-6.97

-6.89

EPCAM

Homo sapiens (Human)

hEGP314; TROP1; TACSTD1; Major gastrointestinal tumor-associated protein GA733-2; MIC18; M4S1; M1S2; KSA; KS 1/4 antigen; Gastrointestinal carcinoma antigen GA733; GA733-2; Epithelial glycoprotein 314

EPCAM family

NA

Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E. May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection.

Diarrhea 5, with tufting enteropathy, congenital (DIAR5) [MIM:613217]: An intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. {ECO:0000269|PubMed:18572020, ECO:0000269|PubMed:24142340}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lynch syndrome 8 (LYNCH8) [MIM:613244]: A form of Lynch syndrome, an autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. Lynch syndrome is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, it is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical Lynch syndrome is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:19098912}. The disease is caused by variants affecting the gene represented in this entry. LYNCH8 results from heterozygous deletion of 3-prime exons of EPCAM and intergenic regions directly upstream of MSH2, resulting in transcriptional read-through and epigenetic silencing of MSH2 in tissues expressing EPCAM.

DB06607; DB11075; DB05831; DB05319; DB09336

P27797; P12830; Q15078; P36957; Q8TDX7

NA

3D-structure; Cell junction; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hereditary nonpolyposis colorectal cancer; Membrane; Proteomics identification; Reference proteome; Repeat; Signal; Tight junction; Transmembrane; Transmembrane helix; Tumor antigen

A

27439.8

243

0.07

33.77

6.03

-1.99

-6.89

SLC22A3

Homo sapiens (Human)

Solute carrier family 22 member 3; Extraneuronal monoamine transporter; EMTH

Major facilitator (TC 2.A.1) superfamily, Organic cation transporter (TC 2.A.1.19) family

NA

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.

Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. 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:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. The disease is caused by variants affecting the gene represented in this entry.

DB00718; DB08838; DB00182; DB00122; DB14006; DB00501; DB00575; DB00363; DB01151; DB00988; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00983; DB00536; DB05381; DB00458; DB00762; DB00709; DB00448; DB08882; DB01042; DB01577; DB00331; DB08893; DB00184; DB00368; DB00526; DB00925; DB00413; DB00457; DB01035; DB00396; DB00938; DB00391; DB13943; DB13944; DB08837; DB08841; DB00541

P00519

NA

3D-structure; Cell membrane; Glycoprotein; Ion transport; Membrane; Mitochondrion; Nucleus; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

A

53067.4

478

0.13

38.82

9.07

10.54

-6.89

CHRNB4

Homo sapiens (Human)

CHRNB4; Beta-4 nAChR

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Beta-4/CHRNB4 sub-subfamily

Neurotransmitter receptor

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.

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.

DB00237; DB00565; DB00514; DB07720; DB00898; DB00472; DB01227; DB00184; DB01090; DB00202

Q6FHY5

NA

3D-structure; Alternative splicing; Cell membrane; Disulfide bond; 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

89661.2

775

0.12

35.11

6.07

-5.67

-6.88

DPP9

Homo sapiens (Human)

Dipeptidyl peptidase-like protein 9; Dipeptidyl peptidase IX; Dipeptidyl peptidase IV-related protein 2; DPRP2; DPRP-2; DPP IX; DPLP9; DP9

Peptidase S9B family, DPPIV subfamily

Peptidase

Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.

Hatipoglu immunodeficiency syndrome (HATIS) [MIM:620331]: An autosomal recessive immunologic disorder manifesting in infancy or early childhood, and characterized by failure to thrive, short stature, skin pigmentation abnormalities, pancytopenia, and susceptibility to recurrent infections. {ECO:0000269|PubMed:36112693}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NXR5; Q86TI2; Q6NUP5; P46379-2; Q8WUW1; Q96A83-2; O75190-2; O14645; Q01658; P29692-2; Q06787-7; Q9Y5Q9; O14901; Q9BVL2; Q96CV9; Q06830; P14678-2; P49458; Q11203; Q13148; P14927

EC 3.4.14.5

3D-structure; Acetylation; Alternative splicing; Aminopeptidase; Cytoplasm; Disease variant; Hydrolase; Nucleus; Protease; Proteomics identification; Reference proteome; Serine protease

A

92797.4

808

0.12

37.45

6.34

-8.98

-6.89

CASP7

Homo sapiens (Human)

MCH3; ICE-like apoptotic protease 3; ICE-LAP3; CMH-1; CASP-7; Apoptotic protease Mch-3

Peptidase C14A family

Peptidase

Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Involved in the activation cascade of caspases responsible for apoptosis execution.

Pregnancy loss, recurrent, 3 (RPRGL3) [MIM:614391]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:17339269}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB05408; DB03384; DB06255

Q13490; P83105; P42858; Q8N4N3-2; P43364; Q16236; Q9GZT8; Q13177; P27986-2; P21673; Q86WV1-2; P17405; P98170

EC 3.4.22.60

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; Apoptosis; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease; Proteomics identification; Reference proteome; RNA-binding; Secreted; Thiol protease; Ubl conjugation; Zymogen

A,B

47441.5

417

0.11

20.98

8.38

6.12

-6.89

treA

Escherichia coli (strain K12)

NA

JW1186;osmA;b1197

Glycosyl hydrolase 37 family

NA

Provides the cells with the ability to utilize trehalose at high osmolarity by splitting it into glucose molecules that can subsequently be taken up by the phosphotransferase-mediated uptake system.

SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells. {ECO:0000269|PubMed:2498394, ECO:0000269|PubMed:3093483}.; DISEASE: Thrombocytopenia 6 (THC6) [MIM:616937]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis. {ECO:0000269|PubMed:26936507}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

3.2.1.28

3D-structure; Direct protein sequencing; Glycosidase; Hydrolase; Periplasm; Reference proteome; Signal

A

57508.9

507

0.11

48.32

5.48

-10.13

-6.87

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

-6.87

RARG

Homo sapiens (Human)

RAR-gamma; Nuclear receptor subfamily 1 group B member 3; NR1B3

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).

Cystic fibrosis (CF) [MIM:219700]: A common generalized disorder of the exocrine glands which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. It is the most common genetic disease in Caucasians, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. {ECO:0000269|PubMed:10094564, ECO:0000269|PubMed:10869121, ECO:0000269|PubMed:10923036, ECO:0000269|PubMed:11242048, ECO:0000269|PubMed:12167682, ECO:0000269|PubMed:12394343, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:1284466, ECO:0000269|PubMed:1284468, ECO:0000269|PubMed:1284529, ECO:0000269|PubMed:1284530, ECO:0000269|PubMed:1284548, ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:15528182, ECO:0000269|PubMed:15716351, ECO:0000269|PubMed:16822950, ECO:0000269|PubMed:1695717, ECO:0000269|PubMed:1699669, ECO:0000269|PubMed:17098864, ECO:0000269|PubMed:1710600, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:20008117, ECO:0000269|PubMed:20150177, ECO:0000269|PubMed:20691141, ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:2236053, ECO:0000269|PubMed:23818989, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27241308, ECO:0000269|PubMed:28001373, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:32026723, ECO:0000269|PubMed:33572515, ECO:0000269|PubMed:7504969, ECO:0000269|PubMed:7505694, ECO:0000269|PubMed:7505767, ECO:0000269|PubMed:7508414, ECO:0000269|PubMed:7513296, ECO:0000269|PubMed:7517264, ECO:0000269|PubMed:7520022, ECO:0000269|PubMed:7522211, ECO:0000269|PubMed:7524909, ECO:0000269|PubMed:7524913, ECO:0000269|PubMed:7525450, ECO:0000269|PubMed:7537150, ECO:0000269|PubMed:7541273, ECO:0000269|PubMed:7541510, ECO:0000269|PubMed:7543567, ECO:0000269|PubMed:7544319, ECO:0000269|PubMed:7581407, ECO:0000269|PubMed:7606851, ECO:0000269|PubMed:7680525, ECO:0000269|PubMed:7683628, ECO:0000269|PubMed:7683954, ECO:0000269|PubMed:8081395, ECO:0000269|PubMed:8406518, ECO:0000269|PubMed:8522333, ECO:0000269|PubMed:8723693, ECO:0000269|PubMed:8723695, ECO:0000269|PubMed:8800923, ECO:0000269|PubMed:8829633, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:8956039, ECO:0000269|PubMed:9101301, ECO:0000269|PubMed:9222768, ECO:0000269|PubMed:9375855, ECO:0000269|PubMed:9401006, ECO:0000269|PubMed:9443874, ECO:0000269|PubMed:9452048, ECO:0000269|PubMed:9452054, ECO:0000269|PubMed:9452073, ECO:0000269|PubMed:9482579, ECO:0000269|PubMed:9507391, ECO:0000269|PubMed:9521595, ECO:0000269|PubMed:9554753, ECO:0000269|PubMed:9736778, ECO:0000269|PubMed:9804160, ECO:0000269|PubMed:9921909}. The disease is caused by variants affecting the gene represented in this entry. There is some evidence that the functional defect caused by the most common variant Phe-508 DEL can be corrected by the binding to the snake phospholipase A2 crotoxin basic subunit CB. This toxin both disrupts the Phe-508 DEL-cytokeratin 8 complex, allowing for the escape from degradation, and increases the chloride channel current (PubMed:27241308). {ECO:0000269|PubMed:27241308}.; DISEASE: Congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]: An autosomal recessive disease characterized by vas deferens aplasia resulting in azoospermia and male infertility. CBAVD may occur in isolation or as a manifestation of cystic fibrosis. {ECO:0000269|PubMed:10066035, ECO:0000269|PubMed:10651488, ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:7529962, ECO:0000269|PubMed:7539342, ECO:0000269|PubMed:9067761, ECO:0000269|PubMed:9736778, ECO:0000269|Ref.117}. The disease is caused by variants affecting the gene represented in this entry.

DB07294; DB07031; DB00459; DB00210; DB00523; DB02466; DB03466; DB02741; DB03279; DB00926; DB00982; DB05785; DB05467; DB02258; DB00799; DB00755; DB12808

Q96RK4; P13349; P31321; P28702; P48443; O60504-2

NA

3D-structure; Alternative splicing; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Methylation; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A

26574.9

236

0.06

49.98

5.76

-2.95

-6.87

BBOX1

Homo sapiens (Human)

NA

BBH;BBOX

Gamma-BBH/TMLD family

Oxidoreductase

Gamma-butyrobetaine dioxygenase activity.Identical protein binding.Iron ion binding.Zinc ion binding.

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.

DB00126

O75936; A0MZ66-7

1.14.11.1

3D-structure; Carnitine biosynthesis; Cytoplasm; Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

31642.5

275

0.12

35.68

6.33

-2.46

-6.87

AGTR1

Homo sapiens (Human)

Type-1 angiotensin II receptor; Angiotensin II type-1 receptor; Angiotensin II receptor 1; Angiotensin 1 receptor; AT2R1B; AT2R1; AT1BR; AT1AR; AT1; AGTR1B; AGTR1A

G-protein coupled receptor 1 family

GPCR rhodopsin

Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Receptor for angiotensin II.

Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. The disease is caused by variants affecting the gene represented in this entry.

DB11842; DB08822; DB13919; DB00796; DB05739; DB00876; DB09279; DB01342; DB01029; DB00678; DB00275; DB01347; DB01349; DB00966; DB00177

PRO_0000032458 [P01019]; P35414; P05026; Q6ZMG9; O75937; P54368

NA

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

A

30770.7

271

0.16

28.86

8.09

2.1

-6.87

MAP2K1

Homo sapiens (Human)

NA

PRKMK1;MEK1

Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily

Transferase

ATP binding.MAP kinase kinase activity.Protein C-terminus binding.Protein kinase activity.Protein N-terminus binding.Protein serine/threonine/tyrosine kinase activity.Protein serine/threonine kinase activator activity.Protein serine/threonine kinase activity.Protein tyrosine kinase activity.Signal transducer, downstream of receptor, with protein tyrosine phosphatase activity.

Cardiofaciocutaneous syndrome 3 (CFC3) [MIM:615279]: A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures. {ECO:0000269|PubMed:16439621, ECO:0000269|PubMed:18042262}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melorheostosis, isolated (MEL) [MIM:155950]: A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma. {ECO:0000269|PubMed:29643386}. The disease is caused by variants affecting the gene represented in this entry.

DB06892; DB07046; DB08208; DB03115; DB11967; DB06616; DB05239; DB02152; DB07101; DB08130; DB14904; DB11689; DB08911

Q8N9N5; Q8N9N5-2; Q9NR09; P15056; Q9Y297; O15519-1; P28482; P27361; Q13526; Q9H8W4; P04049; Q8WWU5-7; Q86Y07; Q86Y07-1; P46937

2.7.12.2

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cardiomyopathy; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant; Ectodermal dysplasia; Intellectual disability; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase

A

34949.2

312

0.07

45.3

5.96

-4.47

-6.87

PDE4C

Homo sapiens (Human)

NA

DPDE1

Cyclic nucleotide phosphodiesterase family, PDE4 subfamily

Hydrolase

3',5'-cyclic-AMP phosphodiesterase activity.Metal ion binding.

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.

DB01427; DB00201; DB05219; DB00651; DB06246; DB05266; DB01088; DB01791; DB01656; DB01954; DB09283

Q96D03; O15499; P26718; P50221; Q6FHY5; Q9UJX0; P26367; P30626; P59817; P30626

3.1.4.53

3D-structure; Alternative splicing; cAMP; Cell projection; Cilium; Hydrolase; Manganese; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

33042.2

291

0.08

23.45

4.91

-18.1

-6.87

PDE4B

Homo sapiens (Human)

cAMP-specific 3',5'-cyclic phosphodiesterase 4B; Type 4B cAMP phosphodiesterase; Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE); PDE32; DPDE4

Cyclic nucleotide phosphodiesterase family, PDE4 subfamily

Phosphoric diester hydrolase

May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

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.

DB04149; DB03606; DB03807; DB06909; DB01959; DB08299; DB03349; DB00131; DB01427; DB00201; DB03849; DB05219; DB01647; DB00651; DB00824; DB02660; DB05266; DB01088; DB01113; DB01791; DB01656; DB01954; DB04530; DB01412; DB00277; DB09283

Q13936; Q08499

EC 3.1.4.53

3D-structure; Alternative splicing; cAMP; Cell membrane; Cytoplasm; Hydrolase; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Zinc

A

37367.1

324

0.08

36.36

5

-20.82

-6.87

KARS

Homo sapiens (Human)

NA

KARS;KIAA0070

Class-II aminoacyl-tRNA synthetase family

ligase / ligase inhibitor

Amino acid binding.ATP adenylyltransferase activity.ATP binding.Identical protein binding.Lysine-tRNA ligase activity.Protein homodimerization activity.TRNA binding.

Charcot-Marie-Tooth disease, recessive intermediate B (CMTRIB) [MIM:613641]: A 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. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:20920668}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 89 (DFNB89) [MIM:613916]: A form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies. {ECO:0000269|PubMed:23768514}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, congenital, and adult-onset progressive leukoencephalopathy (DEAPLE) [MIM:619196]: An autosomal recessive, complex neurodegenerative disorder characterized by congenital sensorineural deafness, and progressive motor and cognitive decline apparent in young adulthood. Brain imaging shows diffuse white matter abnormalities affecting various brain regions, consistent with a progressive leukoencephalopathy. More variable additional features may include visual impairment and axonal peripheral neuropathy. Premature death may occurr in some patients. {ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:30737337, ECO:0000269|PubMed:31116475}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leukoencephalopathy, progressive, infantile-onset, with or without deafness (LEPID) [MIM:619147]: An autosomal recessive, complex neurodegenerative disorder apparent from infancy. LEPID is characterized by early-onset progressive leukoencephalopathy with brainstem and spinal cord calcifications, sensorineural deafness in most patients, global developmental delay with cognitive impairment and poor or absent speech, developmental regression, and neurologic deterioration. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Premature death is common. {ECO:0000269|PubMed:25330800, ECO:0000269|PubMed:29615062, ECO:0000269|PubMed:30252186, ECO:0000269|PubMed:30715177}. The disease is caused by variants affecting the gene represented in this entry.

DB00123

Q13155; P07814; Q15046; P08865; P00441; Q13155

2.7.7.-; 6.1.1.6

3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Cell membrane; Charcot-Marie-Tooth disease; Cytoplasm; Deafness; Direct protein sequencing; Disease variant; Host-virus interaction; Intellectual disability; Ligase; Membrane; Mitochondrion; Neurodegeneration; Neuropathy; Non-syndromic deafness; Nucleotide-binding; Nucleus; Phosphoprotein; Protein biosynthesis; Proteomics identification; Reference proteome; Secreted; Transferase

A,B

37110.4

323

0.1

50.17

4.92

-17.53

-6.88

GLTP

Homo sapiens (Human)

NA

NA

GLTP family

Lipid transport

Glycolipid binding.Glycolipid transporter activity.Identical protein binding.Intermembrane lipid transfer activity.Lipid binding.

Brugada syndrome 7 (BRGDA7) [MIM:613120]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:20031595}. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:20558140, ECO:0000269|PubMed:21051419}. The disease is caused by variants affecting the gene represented in this entry.

DB03600; DB04465; DB03017; DB03203

Q96DZ9; Q9NZD2

NA

3D-structure; Acetylation; Cytoplasm; Lipid transport; Proteomics identification; Reference proteome; Repeat; Transport

A

23534.1

206

0.11

36.45

7.08

0.1

-6.88

VKORC1

Homo sapiens (Human)

Vitamin K1 2,3-epoxide reductase subunit 1; VKORC1; VKOR; UNQ308/PRO351; MSTP576; MSTP134

VKOR family

Short-chain dehydrogenases reductase

Involved invitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.

Combined deficiency of vitamin K-dependent clotting factors 2 (VKCFD2) [MIM:607473]: VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. {ECO:0000269|PubMed:14765194, ECO:0000269|PubMed:16270630}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Coumarin resistance (CMRES) [MIM:122700]: A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement. {ECO:0000269|PubMed:14765194, ECO:0000269|PubMed:20946155}. The disease is caused by variants affecting the gene represented in this entry.

DB01418; DB00266; DB09332; DB00170; DB00498; DB00946; DB01022; DB00682

Q13323; Q7Z7G2; Q96BA8; Q9Y282; Q5JX71; Q96KR6; Q5T7V8; Q8TDT2; Q9NQG1; P15941-11; Q96TC7; Q9NR31; A0A0S2Z4U3; Q8TBB6; O15393-2; Q19QW4

EC 1.17.4.4

3D-structure; Alternative splicing; Disease variant; Disulfide bond; Endoplasmic reticulum; Membrane; Oxidoreductase; Proteomics identification; Quinone; Redox-active center; Reference proteome; Transmembrane; Transmembrane helix

A

42656.4

381

0.1

32.12

7.73

1.93

-6.87