SIGMAR1

Homo sapiens (Human)

hSigmaR1; Sigma1R; Sigma1-receptor; Sigma non-opioid intracellular receptor 1; Sigma 1-type opioid receptor; SRBP; SR31747-binding protein; SR31747 binding protein 1; SR-BP; SIG-1R; Opioid receptor, s

ERG2 family

GPCR rhodopsin

Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration. Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112. Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane.

Amyotrophic lateral sclerosis 16, juvenile (ALS16) [MIM:614373]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:21842496}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, autosomal recessive 2 (HMNR2) [MIM:605726]: A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMNR2 is characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade. {ECO:0000269|PubMed:26078401, ECO:0000269|PubMed:27629094}. The disease is caused by variants affecting the gene represented in this entry.

DB00321; DB09014; DB00907; DB00514; DB01488; DB00574; DB00502; DB00956; DB00704; DB00540; DB06174; DB00652; DB11186; DB03575; DB05316; DB01708; DB00409; DB01104

Q92847-1; Q99720-1; O00213-2; P17612; P50454; P37173

NA

3D-structure; Alternative splicing; Amyotrophic lateral sclerosis; Cell junction; Cell membrane; Cell projection; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Endoplasmic reticulum; Lipid droplet; Lipid transport; Membrane; Neurodegeneration; Neuropathy; Nucleus; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Synapse; Transmembrane; Transmembrane helix; Transport

A

23901

212

0.14

33.12

5.61

-5.6

-8.92

lfrR

Mycolicibacterium smegmatis (Mycobacterium smegmatis)

NA

NA

NA

Transcription

DNA binding.

LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly. {ECO:0000269|PubMed:10896305, ECO:0000269|PubMed:9820300}.

DB01123

NA

NA

3D-structure

A,B,C,D

37947.8

348

0.07

36.27

5.5

-9.3

-8.91

LCMT1

Homo sapiens (Human)

NA

CGI-68;LCMT

Methyltransferase superfamily, LCMT family

Transferase

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

Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) [MIM:617710]: An autosomal recessive, mitochondrial disorder with a broad phenotypic spectrum ranging from severe neonatal lactic acidosis, encephalomyopathy and early death to an attenuated course with milder manifestations. Clinical features include delayed psychomotor development, intellectual disability, hypotonia, dystonia, ataxia, and spasticity. Severe combined respiratory chain deficiency may be found in severely affected individuals. {ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:28650581, ECO:0000269|PubMed:28905505, ECO:0000269|PubMed:30920170, ECO:0000269|PubMed:35074316}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Parkinsonism-dystonia 3, childhood-onset (PKDYS3) [MIM:619738]: An autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. {ECO:0000269|PubMed:29120065, ECO:0000269|PubMed:31970218, ECO:0000269|PubMed:34890876}. The disease is caused by variants affecting the gene represented in this entry.

DB00149

P51116

2.1.1.233

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

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

35803

310

0.08

42.77

6.13

-3.58

-8.91

MAP3K8

Homo sapiens (Human)

Tumor progression locus 2; TPL-2; Proto-oncogene c-Cot; Mitogen-activated protein kinase kinase kinase 8; ESTF; Cancer Osaka thyroid oncogene; COT

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

NA

Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.

Hyperinsulinemic hypoglycemia, familial, 2 (HHF2) [MIM:601820]: A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF2 is a common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF2 inheritance can be autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:10204114, ECO:0000269|PubMed:12364426, ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:15998776, ECO:0000269|PubMed:16332676, ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:18596924, ECO:0000269|PubMed:19357197, ECO:0000269|PubMed:7847376, ECO:0000269|PubMed:8923010}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, permanent neonatal, 2 (PNDM2) [MIM:618856]: A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM2 patients may also have developmental delay, muscle weakness, epilepsy and dysmorphic features. PNDM2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:15115830, ECO:0000269|PubMed:15292329, ECO:0000269|PubMed:15448106, ECO:0000269|PubMed:15448107, ECO:0000269|PubMed:15580558, ECO:0000269|PubMed:15583126, ECO:0000269|PubMed:16609879, ECO:0000269|PubMed:16731833, ECO:0000269|PubMed:17213273, ECO:0000269|PubMed:17652641, ECO:0000269|PubMed:17855752, ECO:0000269|PubMed:20022885, ECO:0000269|PubMed:28842488}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Transient neonatal diabetes mellitus 3 (TNDM3) [MIM:610582]: Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. In a significant number of patients with transient neonatal diabetes mellitus, diabetes type 2 appears later in life. The onset and severity of TNDM3 is variable with childhood-onset diabetes, gestational diabetes or adult-onset diabetes described. {ECO:0000269|PubMed:15718250, ECO:0000269|PubMed:15784703}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2.; DISEASE: Maturity-onset diabetes of the young 13 (MODY13) [MIM:616329]: 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:22701567}. The disease is caused by variants affecting the gene represented in this entry.

NA

P08238; P19838; Q00653; Q13526; Q8NFZ5

EC 2.7.11.25

3D-structure; Alternative initiation; ATP-binding; Cell cycle; Cytoplasm; Immunity; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Reference proteome; Serine/threonine-protein kinase; Transferase

A

34773.8

307

0.09

39.24

6.68

-1.2

-8.91

GRM3

Homo sapiens (Human)

mGLUR3; Group III metabotropic glutamate receptor; GPRC1C

G-protein coupled receptor 3 family

GPCR glutamate

Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity. G-protein coupled receptor for glutamate.

Paramyotonia congenita (PMC) [MIM:168300]: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP. {ECO:0000269|PubMed:10369308, ECO:0000269|PubMed:10727489, ECO:0000269|PubMed:1310898, ECO:0000269|PubMed:1316765, ECO:0000269|PubMed:1338909, ECO:0000269|PubMed:15318338, ECO:0000269|PubMed:15790667, ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:18166706, ECO:0000269|PubMed:18690054, ECO:0000269|PubMed:19077043, ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:8242056, ECO:0000269|PubMed:8308722, ECO:0000269|PubMed:8388676, ECO:0000269|PubMed:8580427}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. {ECO:0000269|PubMed:10599760, ECO:0000269|PubMed:10851391, ECO:0000269|PubMed:10944223, ECO:0000269|PubMed:11558801, ECO:0000269|PubMed:11591859, ECO:0000269|PubMed:16890191, ECO:0000269|PubMed:17898326, ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:20522878, ECO:0000269|PubMed:21043388, ECO:0000269|PubMed:24549961}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of myotonia is found in HYPP patients. {ECO:0000269|PubMed:1659668, ECO:0000269|PubMed:1659948, ECO:0000269|PubMed:20076800}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. {ECO:0000269|PubMed:15596759, ECO:0000269|PubMed:18046642, ECO:0000269|PubMed:20522878}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by exercise. {ECO:0000269|PubMed:10218481, ECO:0000269|PubMed:16786525, ECO:0000269|PubMed:16832098, ECO:0000269|PubMed:17212350, ECO:0000269|PubMed:17998485, ECO:0000269|PubMed:18203179, ECO:0000269|PubMed:18337100, ECO:0000269|PubMed:19015483, ECO:0000269|PubMed:19347921, ECO:0000269|PubMed:20076800, ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:8058156, ECO:0000269|PubMed:9392583}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 16 (CMS16) [MIM:614198]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS16 is characterized by fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation. {ECO:0000269|PubMed:12766226, ECO:0000269|PubMed:25707578, ECO:0000269|PubMed:26659129}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22A, classic (CMYO22A) [MIM:620351]: A form of congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22A is an autosomal recessive form characterized by fetal hypokinesia, polyhydramnios, and severe neonatal hypotonia associated with respiratory insufficiency. Affected individuals who survive the neonatal period have delayed motor development, difficulty walking, proximal muscle weakness of the upper and lower limbs, facial and neck muscle weakness, easy fatigability, and mild limb contractures or foot deformities. {ECO:0000269|PubMed:26700687, ECO:0000269|PubMed:28262468, ECO:0000269|PubMed:36090556}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 22B, severe fetal (CMYO22B) [MIM:620369]: A severe congenital myopathy, a clinically and genetically heterogeneous group of muscle disorders characterized by hypotonia and muscle weakness apparent at birth, and specific pathological features on muscle biopsy. CMYO22B is an autosomal recessive form characterized by onset in utero. Affected individuals show fetal akinesia, and develop fetal hydrops with pulmonary hypoplasia, severe joint contractures, and generalized muscle hypoplasia. Death occurs in utero or soon after birth. {ECO:0000269|PubMed:26700687}. The disease is caused by variants affecting the gene represented in this entry.

DB05096

NA

NA

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

A

50355.5

445

0.11

38.26

6.52

-1.53

-8.9

HCN2

Homo sapiens (Human)

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2; Brain cyclic nucleotide-gated channel 2; BCNG2; BCNG-2

Potassium channel HCN family

Voltage-gated ion channel

Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages. Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions.

Epilepsy, idiopathic generalized 17 (EIG17) [MIM:602477]: A form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. Both autosomal dominant and autosomal recessive EIG17 inheritance have been reported. {ECO:0000269|PubMed:22131395, ECO:0000269|PubMed:29064616}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 2 (FEB2) [MIM:602477]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. FEB2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:24324597}. The disease is caused by variants affecting the gene represented in this entry.

DB02527; DB02315; DB09083

Q9UL51; Q4ACU6-1

NA

3D-structure; Ammonia transport; cAMP; cAMP-binding; Cell membrane; Disease variant; Epilepsy; Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Palmitate; Phosphoprotein; Potassium; Potassium channel; Potassium transport; Proteomics identification; Reference proteome; Sodium; Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; Transport; Voltage-gated channel

A

23672.9

202

0.12

38.05

8.85

4.11

-8.91

HRAS

Homo sapiens (Human)

p21ras; cHras; c-H-ras; Transforming protein p21; HaRas; Ha-Ras; H-Ras-1; GTPase HRas, Nterminally processed

Small GTPase superfamily, Ras family

Small GTPase

Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Involved in the activation of Ras protein signal transduction.

Costello syndrome (CSTLO) [MIM:218040]: A rare condition characterized by prenatally increased growth, postnatal growth deficiency, intellectual disability, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities. {ECO:0000269|PubMed:16170316, ECO:0000269|PubMed:16329078, ECO:0000269|PubMed:16443854, ECO:0000269|PubMed:17054105, ECO:0000269|PubMed:18039947, ECO:0000269|PubMed:18247425, ECO:0000269|PubMed:19995790}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]: Variant of Costello syndrome. {ECO:0000269|PubMed:17412879}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:12727991}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. {ECO:0000269|PubMed:3670300}.; DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas that begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. {ECO:0000269|PubMed:6298635, ECO:0000269|PubMed:6844927}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis. {ECO:0000269|PubMed:22683711}. The disease is caused by variants affecting the gene represented in this entry.

DB04315; DB04137; DB02210; DB08751; DB03226; DB15588

Q99996-3; P53677-2; P10398; Q9NXL2-1; Q9UII2; Q9H7T9; Q00994; Q9H2G9; P15056; Q7Z569; Q5PSV4; Q9ULD4-2; Q96LL4; Q96HB5; Q49A88-3; Q96GN5-2; P24941; O95674; Q9H3R5; Q9Y4F5-3; Q86XR8; Q494V2-2; Q8WUX9; Q14117; Q9Y6W6; O14641; A0AVK6; Q8NB25; Q8IZU1; O94868-3; P15407; P15408; P52655; Q96CS2; Q9BT25; Q8IV36; O43248; Q53GQ0; P10809; Q8NDH6-2; Q8IY31-2; Q8NA54; Q13352; P28290-2; Q9BVG8-5; Q2M2Z5; Q6P597; P57682; Q9UH77; P08727; Q14525; Q14847-2; Q96LR2; P27338; Q99558; Q96EZ8; Q8TAC0; Q5JXC2; Q8NEH6; Q9Y605; Q96HT8; Q9GZM8; P21359; Q8N5V2; Q6PHZ7; Q9BZ95-3; A5D8V7; O43482; Q9BR81; O15534; Q9BUL5; O00329; O00329-2; Q9UPR0; Q96I34; Q15435-3; P04049; P11233; Q15311; Q12967; Q9NS23-2; Q9NS23-4; Q8WWW0; Q8TBY0; Q9P2K3-2; Q9NZL6; O15211; Q8IXN7; Q13671; Q13671-1; Q8WVD3; Q9BY12-3; Q13435; Q12824; Q13573; Q07889; Q86W54-2; Q92783-2; O75886; Q13586; Q8N4C7; O75528; P54274-2; Q9BXU0; Q5T0J7-2; Q5T1C6; Q8IUR5-4; P36406; Q86WT6-2; Q99598; Q6PF05; Q9UGJ1-2; Q9Y5Z9; P22415; Q495M9; Q9H270; Q8NEZ2; P19544-6; O43829; Q9C0F3; Q7Z637; Q86V28; P42337; Q9Z0S9; Q9EQZ6; P27671; Q5EBH1; Q5EBH1-1; P52306-5

NA

3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; Direct protein sequencing; Disease variant; Glycoprotein; Golgi apparatus; GTP-binding; Hydrolase; Isopeptide bond; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus; Palmitate; Prenylation; Proteomics identification; Proto-oncogene; Reference proteome; S-nitrosylation; Ubl conjugation

E,F

28737.2

259

0.1

30.69

5.64

-4.15

-8.9

PORCN

Homo sapiens (Human)

Protein-cysteine N-palmitoyltransferase porcupine; Protein MG61; PORCN

Membrane-bound acyltransferase family, Porcupine subfamily

Acyltransferase

protein-cysteine N-palmitoyltransferase that modulates the processingof Wnt proteins by mediating serine palmitoylation of Wnt family members.

Focal dermal hypoplasia (FODH) [MIM:305600]: A rare congenital ectomesodermal disorder characterized by a combination of skin defects, skeletal abnormalities, and ocular anomalies. Affected individuals have patchy dermal hypoplasia, often in a distribution pattern following the Blaschko lines, and areas of subcutaneous fat herniation or deposition of fat into the dermis. In addition, sparse and brittle hair, hypoplastic nails and papillomas have been described. Skeletal abnormalities usually comprise syndactyly, ectrodactyly, and brachydactyly, and in some cases osteopathia striata has been seen. Patients frequently have ocular anomalies, including microphthalmia/ anophthalmia, coloboma, pigmentary and vascularization defects of the retina. Dental abnormalities are often present. {ECO:0000269|PubMed:17546030, ECO:0000269|PubMed:17546031, ECO:0000269|PubMed:18325042, ECO:0000269|PubMed:19277062, ECO:0000269|PubMed:19309688, ECO:0000269|PubMed:19586929, ECO:0000269|PubMed:19863546, ECO:0000269|PubMed:21472892}. The disease is caused by variants affecting the gene represented in this entry.

NA

P55056; Q8N350-4

EC 2.3.1.250

3D-structure; Acyltransferase; Alternative splicing; Disease variant; Endoplasmic reticulum; Lipoprotein; Membrane; Palmitate; Proteomics identification; Reference proteome; Transferase; Transmembrane; Transmembrane helix; Wnt signaling pathway

A

49013.3

432

0.15

36.17

9.03

11.23

-8.91

NAAA

Homo sapiens (Human)

Nacylsphingosine amidohydrolaselike; Nacylethanolaminehydrolyzing acid amidase subunit beta; NAAA; Acid ceramidaselike protein; ASAHlike protein

Acid ceramidase family

Carbon-nitrogen hydrolase

Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N- palmitoylethanolamine > N-myristoylethanolamine > N- lauroylethanolamine = N-stearoylethanolamine > N- arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N- lauroylsphingosine and N-palmitoylsphingosine.

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

DB09061; DB14009; DB14011

NA

EC 3.5.1.-

3D-structure; Alternative splicing; Autocatalytic cleavage; Direct protein sequencing; Disulfide bond; Fatty acid metabolism; Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism; Lysosome; Membrane; Proteomics identification; Reference proteome; Signal; Zymogen

A,B

36877.8

328

0.11

44.37

7.72

1.08

-8.89

CHRNB2

Homo sapiens (Human)

Nicotinic acetylcholine receptor beta2; Nicotinic acetylcholine receptor beta 2-subunit protein; CHRNB2; Beta-2 nAChR; Alpha-4/beta-2 nicotinic receptor

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Beta-2/CHRNB2 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 permeable to sodiun ions.

Epilepsy, nocturnal frontal lobe, 3 (ENFL3) [MIM:605375]: An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. {ECO:0000269|PubMed:11062464, ECO:0000269|PubMed:11104662}. The disease is caused by variants affecting the gene represented in this entry.

DB00572; DB00237; DB00565; DB09028; DB01245; DB00514; DB07720; DB00898; DB00753; DB00657; DB00333; DB00184; DB00981; DB05458; DB05855; DB05740; DB00747; DB00202; DB01273

P43681-1; P30532

NA

3D-structure; 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

84601.2

728

0.13

39.72

5.86

-9.84

-8.89

SIRT2

Homo sapiens (Human)

SIR2like protein 2; SIR2L2; SIR2L; SIR2-like protein 2; Regulatory protein SIR2 homolog 2; NADdependent protein deacetylase sirtuin2; NAD-dependent protein deacetylase sirtuin-2

Sirtuin family, Class I subfamily

Carbon-nitrogen hydrolase

Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor. NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors.

Deafness, autosomal recessive, 39 (DFNB39) [MIM:608265]: A form of profound prelingual 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:19576567}. The disease is caused by variants affecting the gene represented in this entry.

DB15493

O60566; O60729; P11413; Q92831; Q04206; Q9BYB0; Q12834; Q9UM11

EC 3.5.1.-

3D-structure; Acetylation; Alternative splicing; Autophagy; Cell cycle; Cell division; Cell membrane; Cell projection; Chromosome; Cytoplasm; Cytoskeleton; Differentiation; Immunity; Innate immunity; Meiosis; Membrane; Metal-binding; Microtubule; Mitosis; NAD; Neurodegeneration; Neurogenesis; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Transferase; Ubl conjugation; Zinc

A

34093.1

301

0.1

45.2

5.59

-6.94

-8.89

PGR

Homo sapiens (Human)

PR; Nuclear receptor subfamily 3 group C member 3; NR3C3

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.

Butyrylcholinesterase deficiency (BCHED) [MIM:617936]: An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency. {ECO:0000269|PubMed:10404729, ECO:0000269|PubMed:11928765, ECO:0000269|PubMed:12881446, ECO:0000269|PubMed:1306123, ECO:0000269|PubMed:1349196, ECO:0000269|PubMed:1415224, ECO:0000269|PubMed:15563885, ECO:0000269|PubMed:15781196, ECO:0000269|PubMed:1611188, ECO:0000269|PubMed:16788378, ECO:0000269|PubMed:17700357, ECO:0000269|PubMed:18075469, ECO:0000269|PubMed:18300943, ECO:0000269|PubMed:25054547, ECO:0000269|PubMed:25264279, ECO:0000269|PubMed:2915989, ECO:0000269|PubMed:7634491, ECO:0000269|PubMed:8554068, ECO:0000269|PubMed:8680411, ECO:0000269|PubMed:9110359, ECO:0000269|PubMed:9191541, ECO:0000269|PubMed:9388484, ECO:0000269|PubMed:9543549, ECO:0000269|PubMed:9694584}. The disease is caused by variants affecting the gene represented in this entry.

DB01431; DB06680; DB01406; DB12941; DB13857; DB00304; DB09123; DB01395; DB00378; DB11219; DB00823; DB00294; DB13867; DB08906; DB00588; DB06730; DB11619; DB11064; DB06789; DB00367; DB00431; DB09124; DB00603; DB00351; DB02998; DB00834; DB00648; DB00764; DB14512; DB06713; DB00717; DB00957; DB09389; DB01428; DB02746; DB00396; DB14583; DB00421; DB04787; DB05253; DB08867

Q9H467; P03372; P06401; P40763; P03372

NA

3D-structure; Alternative promoter usage; Alternative splicing; Cytoplasm; Direct protein sequencing; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein; Membrane; Metal-binding; Mitochondrion; Mitochondrion outer membrane; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger

A,B

28853.6

250

0.09

54.82

8.4

2.28

-8.88

cocE

Rhodococcus sp. (strain MB1 Bresler)

NA

NA

CocE/NonD hydrolase family

Hydrolase

Carboxylic ester hydrolase activity.Dipeptidyl-peptidase activity.

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.

DB03793; DB01795

NA

3.1.1.84

3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase; Serine esterase

A

62127.9

574

0.09

26.62

4.56

-33.24

-8.88

Malaria LACZ

Plasmodium falciparum (isolate FCR-3 / Gambia)

LACZ of Plasmodium falciparum (isolate FCR-3 / Gambia); Hypoxanthine phosphoribosyltransferase; HPRT; HGPRTase; HGPRT of Plasmodium falciparum (isolate FCR-3 / Gambia); Guanine phosphoribosyltransfera

Purine/pyrimidine phosphoribosyltransferase family

Pentosyltransferase

Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5- phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Intellectual developmental disorder with dysmorphic facies and ptosis (IDDDFP) [MIM:617333]: An autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and facial dysmorphisms, most notably ptosis. Additional features may include poor growth, hypotonia, and seizures. {ECO:0000269|PubMed:27939639, ECO:0000269|PubMed:27939640}. The disease is caused by variants affecting the gene represented in this entry.

DB02075; DB11638

NA

NA

3D-structure; Cytoplasm; Glycosyltransferase; Magnesium; Metal-binding; Nucleotide-binding; Purine salvage; Transferase

A

26581.3

233

0.12

29.77

7.92

1.69

-8.88

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

-8.89

ALDH1L1

Homo sapiens (Human)

NA

FTHFD

GART family; Aldehyde dehydrogenase family, ALDH1L subfamily

Oxidoreductase

Aldehyde dehydrogenase (NAD) activity.Catalytic activity.Formyltetrahydrofolate dehydrogenase activity.Hydroxymethyl-, formyl- and related transferase activity.

Developmental and epileptic encephalopathy 39 with leukodystrophy (DEE39) [MIM:612949]: 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. DEE39 is characterized by global hypomyelination of the central nervous system, with the gray matter appearing relatively unaffected. Inheritance is autosomal recessive. {ECO:0000269|PubMed:19641205, ECO:0000269|PubMed:24515575}. The disease is caused by variants affecting the gene represented in this entry.

DB00116

Q3SY69; Q92624

1.5.1.6

3D-structure; Acetylation; Alternative splicing; Cytoplasm; NADP; One-carbon metabolism; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Reference proteome

A

33869.5

308

0.08

30.42

6.09

-3.83

-8.86

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

-8.85

FFAR1

Homo sapiens (Human)

NA

GPR40

G-protein coupled receptor 1 family

Fatty acid binding protein / hydrolase

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

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

DB00159

NA

NA

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

A

28319.1

272

0.11

27.3

9.07

6.85

-8.85

FASN

Homo sapiens (Human)

Yeast fatty acid synthase; Fatty-acyl-CoA synthase; Fatty acyl-CoA synthetase enzyme; FAS

NA

Acyltransferase

Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.

Glycine encephalopathy 2 (GCE2) [MIM:620398]: A form of glycine encephalopathy, a metabolic disorder characterized by a high concentration of glycine in the body fluids. Affected individuals typically have severe neurological symptoms, including seizure, lethargy, and muscular hypotonia soon after birth. Most of them die within the neonatal period. Atypical cases have later disease onset and less severely affected psychomotor development. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. The disease is caused by variants affecting the gene represented in this entry.

DB01034; DB01083

Q15848; Q16665; P42858; Q8IV20; Q8TBB1; PRO_0000045603 [Q99IB8]

EC 2.3.1.85

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Proteomics identification; Pyridoxal phosphate; Reference proteome; S-nitrosylation; Transferase; Ubl conjugation

A

30174.9

275

0.09

43.28

5.92

-5.4

-8.86

AR

Homo sapiens (Human)

Testosterone receptor; Nuclear receptor subfamily 3 group C member 4; NR3C4; Dihydrotestosterone receptor; DHTR

Nuclear hormone receptor family, NR3 subfamily

Nuclear hormone receptor

Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.

Androgen insensitivity syndrome (AIS) [MIM:300068]: An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10221770, ECO:0000269|PubMed:10404311, ECO:0000269|PubMed:10458483, ECO:0000269|PubMed:10571951, ECO:0000269|PubMed:10590024, ECO:0000269|PubMed:10690872, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:11744994, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1426313, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:1464650, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:1480178, ECO:0000269|PubMed:1487249, ECO:0000269|PubMed:1569163, ECO:0000269|PubMed:1609793, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:16595706, ECO:0000269|PubMed:1775137, ECO:0000269|PubMed:1999491, ECO:0000269|PubMed:2082179, ECO:0000269|PubMed:2594783, ECO:0000269|PubMed:7537149, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7633398, ECO:0000269|PubMed:7641413, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7962294, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:7981689, ECO:0000269|PubMed:7993455, ECO:0000269|PubMed:8040309, ECO:0000269|PubMed:8096390, ECO:0000269|PubMed:8103398, ECO:0000269|PubMed:8162033, ECO:0000269|PubMed:8224266, ECO:0000269|PubMed:8281140, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8339746, ECO:0000269|PubMed:8413310, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8626869, ECO:0000269|PubMed:8647313, ECO:0000269|PubMed:8683794, ECO:0000269|PubMed:8723113, ECO:0000269|PubMed:8768864, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8830623, ECO:0000269|PubMed:8918984, ECO:0000269|PubMed:8990010, ECO:0000269|PubMed:9001799, ECO:0000269|PubMed:9007482, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9106550, ECO:0000269|PubMed:9160185, ECO:0000269|PubMed:9252933, ECO:0000269|PubMed:9255042, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9328206, ECO:0000269|PubMed:9544375, ECO:0000269|PubMed:9554754, ECO:0000269|PubMed:9610419, ECO:0000269|PubMed:9627582, ECO:0000269|PubMed:9698822, ECO:0000269|PubMed:9851768, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.116, ECO:0000269|Ref.182}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinal and bulbar muscular atrophy X-linked 1 (SMAX1) [MIM:313200]: An X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. {ECO:0000269|PubMed:15851746}. The disease is caused by variants affecting the gene represented in this entry. Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.; DISEASE: Prostate cancer, hereditary, X-linked 3 (HPCX3) [MIM:301120]: A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:8530589}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. {ECO:0000269|PubMed:10363963, ECO:0000269|PubMed:10569618, ECO:0000269|PubMed:1562539, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:17311914, ECO:0000269|PubMed:2260966, ECO:0000269|PubMed:25091737, ECO:0000269|PubMed:8187068, ECO:0000269|PubMed:8274409, ECO:0000269|PubMed:8827083}.; DISEASE: Androgen insensitivity, partial (PAIS) [MIM:312300]: A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10470409, ECO:0000269|PubMed:10502786, ECO:0000269|PubMed:10543676, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:1303262, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1424203, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:2010552, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7649358, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7909256, ECO:0000269|PubMed:7910529, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:8033918, ECO:0000269|PubMed:8097257, ECO:0000269|PubMed:8126121, ECO:0000269|PubMed:8205256, ECO:0000269|PubMed:8281139, ECO:0000269|PubMed:8325932, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8550758, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8823308, ECO:0000269|PubMed:8824883, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9196614, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9329414, ECO:0000269|PubMed:9543136, ECO:0000269|PubMed:9607727, ECO:0000269|PubMed:9768671, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.124}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hypospadias 1, X-linked (HYSP1) [MIM:300633]: A common malformation in which the urethra opens on the ventral side of the penis, due to developmental arrest of urethral fusion. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome and Opitz syndrome. {ECO:0000269|PubMed:8097257}. The disease is caused by variants affecting the gene represented in this entry.

DB07422; DB07039; DB04709; DB07717; DB07454; DB02932; DB08035; DB01481; DB08088; DB08461; DB08087; DB07421; DB01063; DB07423; DB11901; DB01128; DB07286; DB01541; DB14639; DB01564; DB12499; DB04839; DB01406; DB12941; DB09123; DB00255; DB06133; DB01395; DB00858; DB15488; DB11219; DB08899; DB13155; DB00655; DB09086; DB02266; DB01185; DB00623; DB00499; DB11619; DB11064; DB01026; DB15647; DB00367; DB08089; DB05234; DB13934; DB11425; DB06710; DB02998; DB11429; DB00648; DB08804; DB00984; DB00665; DB06713; DB00717; DB09371; DB00957; DB09389; DB00621; DB01428; DB06412; DB01608; DB11447; DB01708; DB00396; DB07419; DB07769; DB14583; DB00421; DB02901; DB13951; DB06718; DB00675; DB00624; DB13943; DB13944; DB01420; DB13946; DB06870; DB08604; DB08867

P00519; Q9UBL3; P51451; Q8WV28; O60885-1; P78543; Q14790; P24385; Q92793; O14595; P35222; Q9UER7; P20711; P11308; P07332; P09769; Q02790; P55317; O75593; Q14451; P06396; P56524; Q16665; Q16666; O15357; Q15652; O95251; Q9BY66; Q9BY66-3; Q03164; O14686; P06239; P07948; P20794; P42679; Q00987; Q15596; Q14686; O96028; Q99497; P27986; O00459; Q92569; P19174; P16885; Q06830; P78527; Q06124; P20936; Q9UBS8; Q9Y252; O14796; Q9NP31; P29353; Q6S5L8; Q5VZ18; Q15797; O14544; P12931; Q9ULZ2; P63165; Q9HBL0; P07947; Q9R1E0; Q06986

NA

3D-structure; Activator; Alternative splicing; Cytoplasm; Disease variant; DNA-binding; Isopeptide bond; Lipid-binding; Lipoprotein; Metal-binding; Neurodegeneration; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Pseudohermaphroditism; Receptor; Reference proteome; Steroid-binding; Transcription; Transcription regulation; Triplet repeat expansion; Ubl conjugation; Zinc; Zinc-finger

A

29137.9

250

0.11

42.11

8.94

5.43

-8.85