F10

Homo sapiens (Human)

Fxa; Factor Xa; F10; Activated coagulation factor X

Peptidase S1 family

Peptidase

Factor Xa is avitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Factor X deficiency (FA10D) [MIM:227600]: A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis. {ECO:0000269|PubMed:10468877, ECO:0000269|PubMed:10739379, ECO:0000269|PubMed:10746568, ECO:0000269|PubMed:11248282, ECO:0000269|PubMed:11728527, ECO:0000269|PubMed:12574802, ECO:0000269|PubMed:12945883, ECO:0000269|PubMed:15075089, ECO:0000269|PubMed:15650540, ECO:0000269|PubMed:17393015, ECO:0000269|PubMed:19135706, ECO:0000269|PubMed:1973167, ECO:0000269|PubMed:1985698, ECO:0000269|PubMed:25313940, ECO:0000269|PubMed:26222694, ECO:0000269|PubMed:2790181, ECO:0000269|PubMed:7669671, ECO:0000269|PubMed:7860069, ECO:0000269|PubMed:8529633, ECO:0000269|PubMed:8845463, ECO:0000269|PubMed:8910490}. The disease is caused by variants affecting the gene represented in this entry.

DB07211; DB08746; DB07974; DB07277; DB07605; DB08487; DB08495; DB04673; DB08745; DB08488; DB07804; DB08174; DB08173; DB07872; DB07843; DB07848; DB07875; DB08143; DB07847; DB07844; DB13884; DB06552; DB13151; DB13192; DB00025; DB11166; DB06605; DB09258; DB12364; DB00100; DB13152; DB13150; DB00036; DB09075; DB16662; DB13923; DB01225; DB06920; DB00569; DB03847; DB07278; DB01109; DB06406; DB09332; DB06245; DB13998; DB05713; DB13999; DB07630; DB07629; DB07973; DB07800; DB12598; DB13933; DB06635; DB09141; DB13149; DB11311; DB06228; DB05362; DB07261; DB08426; DB09109; DB14738

P0DPK4; Q9UK55; Q9UHD9

EC 3.4.21.6

3D-structure; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; EGF-like domain; Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydrolase; Hydroxylation; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Zymogen

A

31315.2

280

0.09

38.33

6.36

-1.82

-9.8

CYP51A1

Homo sapiens (Human)

Cytochrome P450LI; Cytochrome P45014DM; Cytochrome P450-14DM; Cytochrome P450 51A1

Cytochrome P450 family

Cytochrome P450 family

Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.

Spondyloepimetaphyseal dysplasia, short limb-hand type (SEMD-SL) [MIM:271665]: A bone disease characterized by short-limbed dwarfism, a narrow chest with pectus excavatum, brachydactyly in the hands and feet, a characteristic craniofacial appearance and premature calcifications. The radiological findings are distinctive and comprise short long bones throughout the skeleton with striking epiphyses that are stippled, flattened and fragmented and flared, irregular metaphyses. Platyspondyly in the spine with wide intervertebral spaces is observed and some vertebral bodies are pear-shaped with central humps, anterior protrusions and posterior scalloping. {ECO:0000269|PubMed:19110212, ECO:0000269|PubMed:20223752, ECO:0000269|PubMed:26463668}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Warburg-Cinotti syndrome (WRCN) [MIM:618175]: An autosomal dominant disease characterized by progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acro-osteolysis. {ECO:0000269|PubMed:30449416}. The disease is caused by variants affecting the gene represented in this entry.

DB07705; DB05667; DB01110; DB01007

NA

EC 1.14.14.154

3D-structure; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix

A,B,C,D

53013.3

462

0.11

47.66

8.8

7

-10.28

ECE1

Homo sapiens (Human)

ECE-1

Peptidase M13 family

Peptidase

Converts big endothelin-1 to endothelin-1.

Hirschsprung disease, cardiac defects, and autonomic dysfunction (HCAD) [MIM:613870]: A disorder characterized by skip-lesions Hirschsprung disease, craniofacial abnormalities and other dysmorphic features, cardiac defects including ductus arteriosus, small subaortic ventricular septal defect, small atrial septal defect, and autonomic dysfunction. {ECO:0000269|PubMed:9915973}. The disease is caused by variants affecting the gene represented in this entry.

DB07171

P49760; A8MQ03; Q8IUG1; P60370; P60410

EC 3.4.24.71

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Hirschsprung disease; Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Zinc

A

75247.9

660

0.12

46.29

5.33

-18.3

-9.9

F2

Homo sapiens (Human)

NA

NA

Peptidase S1 family

Hydrolase

Calcium ion binding.Growth factor activity.Heparin binding.Lipopolysaccharide binding.Receptor binding.Serine-type endopeptidase activity.Thrombospondin receptor activity.

Factor II deficiency (FA2D) [MIM:613679]: A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels. {ECO:0000269|PubMed:1349838, ECO:0000269|PubMed:1354985, ECO:0000269|PubMed:1421398, ECO:0000269|PubMed:14962227, ECO:0000269|PubMed:2719946, ECO:0000269|PubMed:3242619, ECO:0000269|PubMed:3567158, ECO:0000269|PubMed:3771562, ECO:0000269|PubMed:3801671, ECO:0000269|PubMed:6405779, ECO:0000269|PubMed:7792730, ECO:0000269|PubMed:7865694}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:15534175}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Thrombophilia due to thrombin defect (THPH1) [MIM:188050]: A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. {ECO:0000269|PubMed:2825773}. The disease is caused by variants affecting the gene represented in this entry. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.; DISEASE: Pregnancy loss, recurrent, 2 (RPRGL2) [MIM:614390]: 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:11506076}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB07211; DB07796; DB07016; DB07521; DB06850; DB07091; DB06845; DB07088; DB07131; DB07095; DB07515; DB07897; DB06878; DB06947; DB08624; DB06869; DB06929; DB07400; DB04771; DB04772; DB02287; DB07277; DB07550; DB07549; DB07548; DB07105; DB04722; DB07366; DB08254; DB01725; DB08062; DB07639; DB07461; DB07120; DB07190; DB07741; DB07353; DB07508; DB07809; DB08546; DB08061; DB07718; DB03136; DB02723; DB07440; DB07376; DB06861; DB06866; DB06865; DB03865; DB06841; DB07934; DB08422; DB07659; DB07660; DB07658; DB13151; DB00025; DB11166; DB00278; DB01766; DB07083; DB00006; DB00100; DB13152; DB09228; DB09130; DB03159; DB06911; DB06996; DB06919; DB07027; DB07133; DB07143; DB07005; DB06695; DB00055; DB01225; DB05714; DB12831; DB03847; DB07278; DB01767; DB06404; DB09332; DB00001; DB13998; DB04136; DB00170; DB06838; DB13999; DB06868; DB06942; DB06936; DB07165; DB07527; DB07522; DB07665; DB07946; DB06859; DB06853; DB06858; DB07279; DB08187; DB04591; DB07944; DB07128; DB12598; DB01123; DB04786; DB05777; DB04697; DB09109; DB14738; DB04898; DB01593; DB14487; DB08152

P05067; P07204; Q846V4; PRO_0000032489 [P01008]

3.4.21.5

3D-structure; Acute phase; Blood coagulation; Calcium; Cleavage on pair of basic residues; Direct protein sequencing; Disease variant; Disulfide bond; Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis; Hydrolase; Kringle; Pharmaceutical; Protease; Proteomics identification; Reference proteome; Repeat; Secreted; Serine protease; Signal; Thrombophilia; Zymogen

H

29321.6

254

0.1

39.57

8.56

4.16

-9.12

GAST

Homo sapiens (Human)

Gastrin6; GAST; G52; G34; G14

Gastrin/cholecystokinin family

Gastrin cholecystokinin

Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.

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.

DB12532

Q13520; O43315; Q12797-6; Q9BXK5; Q8N5K1; Q96BA8; P00387; Q9Y282; Q5JX71; Q8NBJ4; Q8TDT2; P43628; O76011; Q6ZUX7; Q15546; P15941-11; Q13113; P60201-2; Q14973; P02787; Q4KMG9

NA

3D-structure; Amidation; Cleavage on pair of basic residues; Direct protein sequencing; Hormone; Phosphoprotein; Proteomics identification; Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal; Sulfation

A,F

31827.9

280

0.08

41.06

8.84

5.56

-9.4

KLK5

Homo sapiens (Human)

UNQ570/PRO1132; Stratum corneum tryptic enzyme; SCTE; Kallikrein-like protein 2; KLK-L2

Peptidase S1 family, Kallikrein subfamily

Peptidase

May be involved in desquamation.

Lipodystrophy, familial partial, 8 (FPLD8) [MIM:620679]: An autosomal dominant form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD8 patients show selective loss of subcutaneous adipose tissue from the limbs, beginning around 13 to 15 years of age, and abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia. {ECO:0000269|PubMed:27376152}. The disease may be caused by variants affecting the gene represented in this entry.

NA

P20930; Q9NQG1

EC 3.4.21.-

3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Protease; Proteomics identification; Reference proteome; Secreted; Serine protease; Signal

A,B

50299.2

454

0.07

40.74

9.25

23.09

-10.17

ECE1

Homo sapiens (Human)

ECE-1

Peptidase M13 family

Peptidase

Converts big endothelin-1 to endothelin-1.

Hirschsprung disease, cardiac defects, and autonomic dysfunction (HCAD) [MIM:613870]: A disorder characterized by skip-lesions Hirschsprung disease, craniofacial abnormalities and other dysmorphic features, cardiac defects including ductus arteriosus, small subaortic ventricular septal defect, small atrial septal defect, and autonomic dysfunction. {ECO:0000269|PubMed:9915973}. The disease is caused by variants affecting the gene represented in this entry.

DB07171

P49760; A8MQ03; Q8IUG1; P60370; P60410

EC 3.4.24.71

3D-structure; Alternative splicing; Cell membrane; Disease variant; Disulfide bond; Glycoprotein; Hirschsprung disease; Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Zinc

A

75247.9

660

0.12

46.29

5.33

-18.3

-9.99

fkbI

Streptomyces hygroscopicus subsp. ascomyceticus

NA

NA

Acyl-CoA dehydrogenase family

Oxidoreductase

Flavin adenine dinucleotide binding.Oxidoreductase activity, acting on the CH-CH group of donors.

Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (THMD5) [MIM:614458]: An autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits. {ECO:0000269|PubMed:22152682}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

NA

3D-structure; FAD; Flavoprotein; Nucleotide-binding; Oxidoreductase

A

36670.3

353

0.04

22.05

6.12

-5.04

-9.83

pol

Human immunodeficiency virus type 1 (HIV-1)

NA

NA

NA

Hydrolase / hydrolase inhibitor

Aspartic-type endopeptidase 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.

DB00701; DB01072; DB04887; DB01264; DB01319; DB00224; DB01601; DB00503; DB01232; DB00932

NA

NA

3D-structure; Aspartyl protease; Hydrolase; Protease

A,B

21411

198

0.05

42.78

9.45

4.15

-10.48

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

-10.88

PDE4D

Homo sapiens (Human)

cAMP-specific 3',5'-cyclic phosphodiesterase 4D; PDE43; DPDE3

Cyclic nucleotide phosphodiesterase family, PDE4 subfamily

Phosphoric diester hydrolase

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. {ECO:0000269|PubMed:17006457}.; DISEASE: Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems. {ECO:0000269|PubMed:22464250, ECO:0000269|PubMed:22464252, ECO:0000269|PubMed:23033274, ECO:0000269|PubMed:23043190}. The disease is caused by variants affecting the gene represented in this entry.

DB06842; DB04149; DB03606; DB03183; DB04469; DB02676; DB01959; DB07051; DB04271; DB07954; DB08299; DB00131; DB01427; DB00201; DB03849; DB05219; DB00651; DB06246; DB05266; DB01088; DB01113; DB01791; DB01656; DB01954; DB05298; DB09283; DB02918

P32121; P38432; Q0D2H9; Q08AF8; P43360; Q07343; Q13077; P32121; P26769; P38432; Q96CV9; Q8IUH5

EC 3.1.4.53

3D-structure; Alternative splicing; cAMP; Cell membrane; Cytoplasm; Cytoskeleton; Disease variant; Hydrolase; Isopeptide bond; Manganese; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Ubl conjugation; Zinc

A,B

37201.9

322

0.07

35.83

5.02

-21.16

-10.81

GP6

Homo sapiens (Human)

Glycoprotein 6; GPVI

NA

NA

Collagen receptor involved in collagen-induced platelet adhesion and activation. Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2.

Bleeding disorder, platelet-type, 11 (BDPLT11) [MIM:614201]: A mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen. {ECO:0000269|PubMed:19549989, ECO:0000269|PubMed:19552682}. The disease is caused by variants affecting the gene represented in this entry.

NA

P06241; P07948; P06241; P07948

NA

3D-structure; Alternative splicing; Blood coagulation; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Hemostasis; Immunoglobulin domain; Membrane; Proteomics identification; Receptor; Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix

A

19027.4

173

0.11

37.14

8.68

2.52

-8.2

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

-10.91

TRPC5

Homo sapiens (Human)

hTRP5; hTRP-5; TrpC5; Transient receptor protein 5; TRP-5

Transient receptor (TC 1.A.4) family, STrpC subfamily, TRPC5 sub-subfamily

Transient receptor potential catioin channel

Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective. May also be activated by intracellular calcium store depletion.

Loss-of-function variants in TRPC5 may be involved in a mental disorder characterized by maladaptive behavior, anxiety, autism, postpartum depression, extreme food-seeking and hoarding behavior, hyperphagia and obesity. {ECO:0000269|PubMed:38959890}.

NA

NA

NA

3D-structure; ANK repeat; Calcium; Calcium channel; Calcium transport; Cell membrane; Disease variant; Glycoprotein; Ion channel; Ion transport; Membrane; Proteomics identification; Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport

A

76850.6

665

0.12

40.05

6.16

-5.94

-11.15

OPRD1

Homo sapiens (Human)

OPRD; Delta-type opioid receptor; Delta opioid receptor; DOR-1; D-OR-1

G-protein coupled receptor 1 family

GPCR rhodopsin

Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine. G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids.

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

DB01571; DB01439; DB05050; DB06274; DB06288; DB00321; DB01238; DB00921; DB00611; DB09173; DB09061; DB01535; DB00318; DB00514; DB00647; DB01452; DB01565; DB01444; DB01081; DB01548; DB09272; DB01497; DB00813; DB00956; DB00327; DB01221; DB06738; DB00854; DB00836; DB14146; DB14009; DB12668; DB00333; DB00295; DB06409; DB14011; DB00844; DB11691; DB06230; DB01183; DB00704; DB11130; DB00497; DB01192; DB09209; DB00899; DB12543; DB00708; DB06204; DB00193

P16615; P27824; Q4LDR2; Q5JY77; Q9NS64; Q9Y666-2; Q9UKG4; Q0VAQ4; Q96Q45-2; P11607

NA

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

A

32859.3

294

0.11

33.86

9.38

13.6

-10.1

MAP3K20

Homo sapiens (Human)

ZAK; Sterile alpha motif- and leucine zipper-containing kinase AZK; Mixed lineage kinase-related kinase; Mitogen-activated protein kinase kinase kinase MLT; Mitogen-activated protein kinase kinase kin

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

NA

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Involved in limb development.

Split-foot malformation with mesoaxial polydactyly (SFMMP) [MIM:616890]: An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss. {ECO:0000269|PubMed:26755636, ECO:0000269|PubMed:32266845}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6) [MIM:617760]: A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood. {ECO:0000269|PubMed:27816943, ECO:0000269|PubMed:30237576}. The disease is caused by variants affecting the gene represented in this entry.

DB01254; DB12010

O75582; P31947; P63104; Q8N184; Q16512; Q6P2D0; Q6ZN57; P13682; Q8N184; Q6AZW8; Q9NQZ8

EC 2.7.11.25

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cytoplasm; Disease variant; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; RNA-binding; rRNA-binding; Serine/threonine-protein kinase; Transferase

A,B

64591.5

566

0.1

52.08

5.69

-12.83

-11.04

GLP1R

Homo sapiens (Human)

GLP-1R; GLP-1-R; GLP-1 receptor

G-protein coupled receptor 2 family

GPCR secretin

Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels. Plays a role in regulating insulin secretion in response to GLP-1. G-protein coupled receptor for glucagon-like peptide 1 (GLP-1).

Lynch syndrome 2 (LYNCH2) [MIM:609310]: 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:10323887, ECO:0000269|PubMed:10375096, ECO:0000269|PubMed:10386556, ECO:0000269|PubMed:10413423, ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10598809, ECO:0000269|PubMed:10627141, ECO:0000269|PubMed:10660333, ECO:0000269|PubMed:10671064, ECO:0000269|PubMed:10713887, ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:10882759, ECO:0000269|PubMed:11139242, ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:11748856, ECO:0000269|PubMed:11754112, ECO:0000269|PubMed:11781295, ECO:0000269|PubMed:11793442, ECO:0000269|PubMed:11839723, ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:12095971, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:12655562, ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14635101, ECO:0000269|PubMed:14961575, ECO:0000269|PubMed:15064764, ECO:0000269|PubMed:15139004, ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:15365996, ECO:0000269|PubMed:16083711, ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:17301300, ECO:0000269|PubMed:17510385, ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22753075, ECO:0000269|PubMed:7757073, ECO:0000269|PubMed:8566964, ECO:0000269|PubMed:8571956, ECO:0000269|PubMed:8574961, ECO:0000269|PubMed:8797773, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:8993976, ECO:0000269|PubMed:9048925, ECO:0000269|PubMed:9067757, ECO:0000269|PubMed:9218993, ECO:0000269|PubMed:9272156, ECO:0000269|PubMed:9298827, ECO:0000269|PubMed:9311737, ECO:0000269|PubMed:9326924, ECO:0000269|PubMed:9399661, ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9718327, ECO:0000269|PubMed:9833759, ECO:0000269|PubMed:9927034, ECO:0000269|Ref.5}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mismatch repair cancer syndrome 1 (MMRCS1) [MIM:276300]: An autosomal recessive form of mismatch repair cancer syndrome, a childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. {ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:17440981, ECO:0000269|PubMed:7661930}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269|PubMed:8751876}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in MLH1 may contribute to lobular carcinoma in situ (LCIS), a non-invasive neoplastic disease of the breast.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Some epigenetic changes can be transmitted unchanged through the germline (termed 'epigenetic inheritance'). Evidence that this mechanism occurs in humans is provided by the identification of individuals in whom 1 allele of the MLH1 gene is epigenetically silenced throughout the soma (implying a germline event). These individuals are affected by Lynch syndrome but does not have identifiable mutations in MLH1, even though it is silenced, which demonstrates that an epimutation can phenocopy a genetic disease.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:10598809, ECO:0000269|PubMed:10882759, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:15184898, ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9032648, ECO:0000269|PubMed:9087566, ECO:0000269|PubMed:9611074}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB09043; DB09045; DB15650; DB01276; DB00040; DB16697; DB06655; DB09265; DB13928; DB14027; DB15171

A8MQ03; Q07627; Q8IUG1; P60409; P60410; P60411; Q9BYP8; P26371; Q7Z3S9; P0DPK4

NA

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

R

45579.6

390

0.16

39.66

6.73

-0.68

-11.94

TMPRSS15

Homo sapiens (Human)

Transmembrane protease serine 15; TMPRSS15; Serine protease 7; Enterokinase

Peptidase S1 family

Peptidase

Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.

Enterokinase deficiency (ENTKD) [MIM:226200]: Life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive. {ECO:0000269|PubMed:11719902}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.21.9

3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lipoprotein; Membrane; Myristate; Protease; Proteomics identification; Reference proteome; Repeat; Serine protease; Signal-anchor; Transmembrane; Transmembrane helix; Zymogen

A

26220.3

234

0.1

50.13

4.82

-9.93

-8.58

CASR

Homo sapiens (Human)

hCasR; Parathyroid cell calciumreceptor; Parathyroid cell calcium-sensing receptor 1; Parathyroid calcium receptor; Parathyroid Cell calcium-sensing receptor; PCaR1; GPRC2A; CaSR

G-protein coupled receptor 3 family

GPCR glutamate

Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation. G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis.

Hypocalciuric hypercalcemia, familial 1 (HHC1) [MIM:145980]: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults. {ECO:0000269|PubMed:11762699, ECO:0000269|PubMed:15572418, ECO:0000269|PubMed:15579740, ECO:0000269|PubMed:15879434, ECO:0000269|PubMed:16598859, ECO:0000269|PubMed:16740594, ECO:0000269|PubMed:17473068, ECO:0000269|PubMed:17698911, ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:19789209, ECO:0000269|PubMed:21566075, ECO:0000269|PubMed:21643651, ECO:0000269|PubMed:22114145, ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, ECO:0000269|PubMed:25104082, ECO:0000269|PubMed:25292184, ECO:0000269|PubMed:26386835, ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:7673400, ECO:0000269|PubMed:7726161, ECO:0000269|PubMed:7916660, ECO:0000269|PubMed:8636323, ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9298824}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperparathyroidism, neonatal severe (NSHPT) [MIM:239200]: A disorder characterized by severe hypercalcemia, bone demineralization, and failure to thrive usually manifesting in the first 6 months of life. If untreated, NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy. {ECO:0000269|PubMed:14985373, ECO:0000269|PubMed:15572418, ECO:0000269|PubMed:17555508, ECO:0000269|PubMed:27434672, ECO:0000269|PubMed:8675635, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9253359}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypocalcemia, autosomal dominant 1 (HYPOC1) [MIM:601198]: A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia. {ECO:0000269|PubMed:10487661, ECO:0000269|PubMed:12050233, ECO:0000269|PubMed:12107202, ECO:0000269|PubMed:12241879, ECO:0000269|PubMed:12574188, ECO:0000269|PubMed:12915654, ECO:0000269|PubMed:15551332, ECO:0000269|PubMed:16608894, ECO:0000269|PubMed:19179454, ECO:0000269|PubMed:22789683, ECO:0000269|PubMed:23169696, ECO:0000269|PubMed:23966241, ECO:0000269|PubMed:25766501, ECO:0000269|PubMed:7874174, ECO:0000269|PubMed:8702647, ECO:0000269|PubMed:8733126, ECO:0000269|PubMed:8813042, ECO:0000269|PubMed:8878438, ECO:0000269|PubMed:9253358, ECO:0000269|PubMed:9661634, ECO:0000269|PubMed:9920108}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Epilepsy, idiopathic generalized 8 (EIG8) [MIM:612899]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures. {ECO:0000269|PubMed:18756473}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

DB11093; DB11348; DB14481; DB01012; DB12865; DB00994; DB05695; DB05255; DB00127

Q15363; P41180-1

NA

3D-structure; Alternative splicing; Calcium; Cell membrane; Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation

A,B

52438.9

467

0.12

39.62

5.63

-10.18

-10.46

FABP5

Homo sapiens (Human)

Psoriasis-associated fatty acid-binding protein homolog; PA-FABP; Fatty acid-binding protein, epidermal; Fatty Acid BindingProtein mal1; Epidermal-type fatty acid-binding protein; E-FABP

Calycin superfamily, Fatty-acid binding protein (FABP) family

Fatty acid binding protein

Intracellular carrier for long-chain fatty acids and related active lipids, such as the endocannabinoid, that regulates the metabolism and actions of the ligands they bind. In addition to the cytosolic transport, selectively delivers specific fatty acids from the cytosol to the nucleus, wherein they activate nuclear receptors. Delivers retinoic acid to the nuclear receptor peroxisome proliferator-activated receptor delta; which promotes proliferation and survival. May also serve as a synaptic carrier of endocannabinoid at central synapses and thus controls retrograde endocannabinoid signaling. Modulates inflammation by regulating PTGES induction via NF-kappa-B activation, and prostaglandin E2 (PGE2) biosynthesis during inflammation. May be involved in keratinocyte differentiation.

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

DB03796

NA

NA

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Disulfide bond; Lipid transport; Lipid-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Secreted; Synapse; Transport

A

15033.1

134

0.06

28.26

6.83

-0.14

-9.97