GABBR1

Homo sapiens (Human)

NA

GPRC3B;GPR51

G-protein coupled receptor 3 family, GABA-B receptor subfamily

Signaling protein / antagonist

G-protein coupled GABA receptor activity.

Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS) [MIM:617903]: An autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability. {ECO:0000269|PubMed:26740508, ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 59 (DEE59) [MIM:617904]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy. {ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29100083, ECO:0000269|PubMed:29369404}. The disease is caused by variants affecting the gene represented in this entry.

DB08891; DB08892; DB00181; DB00363; DB02530; DB05010; DB09072

Q9UBS5; Q9UBS5-2; P46459; Q86UR5

NA

3D-structure; Cell membrane; Coiled coil; Direct protein sequencing; Disease variant; Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; Intellectual disability; Membrane; Phosphoprotein; Postsynaptic cell membrane; Proteomics identification; Receptor; Reference proteome; Signal; Synapse; Transducer; Transmembrane; Transmembrane helix

A

46502.1

408

0.12

50.05

5.78

-5.62

-9.51

Cory pafA

Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / JCM 1318 / BCRC 11384 / CCUG 27702 / LMG 3730 / NBRC 12168 / NCIMB 10025 / NRRL B-2784 / 534)

Pup-conjugating enzyme; Pup--protein ligase; Proteasome accessory factor A

Pup ligase/Pup deamidase family, Pup-conjugating enzyme subfamily

NA

Catalyzes the covalent attachment of the prokaryotic ubiquitin-like protein modifier Pup to the proteasomal substrate proteins, thereby targeting them for proteasomal degradation. This tagging system is termed pupylation. The ligation reaction involves the side-chain carboxylate of the C-terminal glutamate of Pup and the side-chain amino group of a substrate lysine.

Anemia, non-spherocytic hemolytic, due to G6PD deficiency (NSHA) [MIM:300908]: A disease characterized by G6PD deficiency, acute hemolytic anemia, fatigue, back pain, and jaundice. In most patients, the disease is triggered by an exogenous agent, such as some drugs, food, or infection. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. Although G6PD deficiency can be life-threatening, most patients are asymptomatic throughout their life. {ECO:0000269|PubMed:12524354, ECO:0000269|PubMed:1303180, ECO:0000269|PubMed:1303182, ECO:0000269|PubMed:1536798, ECO:0000269|PubMed:1611091, ECO:0000269|PubMed:1889820, ECO:0000269|PubMed:1945893, ECO:0000269|PubMed:20007901, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:2836867, ECO:0000269|PubMed:2912069, ECO:0000269|PubMed:30988594, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:7858267, ECO:0000269|PubMed:7959695, ECO:0000269|PubMed:8193373, ECO:0000269|PubMed:8490627, ECO:0000269|PubMed:8533762, ECO:0000269|PubMed:8733135, ECO:0000269|PubMed:9452072}. The disease is caused by variants affecting the gene represented in this entry. Deficiency of G6PD is associated with hemolytic anemia in two different situations. First, in areas in which malaria has been endemic, G6PD-deficiency alleles have reached high frequencies (1% to 50%) and deficient individuals, though essentially asymptomatic in the steady state, have a high risk of acute hemolytic attacks. Secondly, sporadic cases of G6PD deficiency occur at a very low frequencies, and they usually present a more severe phenotype. Several types of NSHA are recognized. Class-I variants are associated with severe NSHA; class-II have an activity <10% of normal; class-III have an activity of 10% to 60% of normal; class-IV have near normal activity.

NA

NA

NA

3D-structure; ATP-binding; Ligase; Magnesium; Metal-binding; Nucleotide-binding; Reference proteome; Ubl conjugation pathway

A,B

110572

994

0.07

42.33

5.26

-34.19

-8.59

HMGCR

Homo sapiens (Human)

3-hydroxy-3-methylglutaryl-coenzyme A reductase

HMG-CoA reductase family

CH-OH donor oxidoreductase

Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.

Muscular dystrophy, limb-girdle, autosomal recessive 28 (LGMDR28) [MIM:620375]: An autosomal recessive form of limb girdle muscular dystrophy, a group of genetically heterogeneous muscular disorders that share proximal muscle weakness as the major attribute. Most limb girdle muscular dystrophies present with elevated creatinine kinase and myopathic electromyographic features. Disease is usually progressive to a variable degree, ranging from minor disability to complete inability to ambulate, and can involve the large proximal muscles, as well as axial and facial muscles. Different disease forms may exhibit skeletal muscle hypertrophy, kyphoscoliosis, and contractures or involve other muscle groups and manifest with distal weakness, cardiomyopathy, dysphagia, and respiratory difficulties. LGMDR28 is characterized by progressive muscle weakness affecting the proximal and axial muscles of the upper and lower limbs, and highly variable age at onset. Most patients have limited ambulation or become wheelchair-bound within a few decades, and respiratory insufficiency commonly occurs. {ECO:0000269|PubMed:36745799, ECO:0000269|PubMed:37167966}. The disease is caused by variants affecting the gene represented in this entry.

DB03169; DB04447; DB01076; DB09061; DB00439; DB01992; DB01095; DB00227; DB14009; DB04377; DB06693; DB14011; DB00157; DB03461; DB08860; DB00175; DB01098; DB00641; DB05317; DB09270

Q9Y5Z9; Q9Y5Z9-1

EC 1.1.1.34

3D-structure; Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism; Disease variant; Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Limb-girdle muscular dystrophy; Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase; Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation

A,B,C,D

84796.9

798

0.05

47.61

6.2

-3.71

-7.69

UBA3

Homo sapiens (Human)

Ubiquitin-like modifier-activating enzyme 3; Ubiquitin-activating enzyme E1C; Ubiquitin-activating enzyme 3; UBE1C; NEDD8-activating enzyme E1 catalytic subunit

Ubiquitin-activating E1 family, UBA3 subfamily

Carbon-sulfur ligase

E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression. Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme.

Galactosemia 3 (GALAC3) [MIM:230350]: A form of galactosemia, an inborn error of galactose metabolism typically manifesting in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. GALAC3 is an autosomal recessive form caused by galactose epimerase deficiency. It can manifest as benign, peripheral form with mild symptoms and enzymatic deficiency in circulating blood cells only. A second form, known as generalized epimerase deficiency, is characterized by undetectable levels of enzyme activity in all tissues and severe clinical features, including restricted growth and intellectual disability. {ECO:0000269|PubMed:11279193, ECO:0000269|PubMed:11903335, ECO:0000269|PubMed:15639193, ECO:0000269|PubMed:16301867, ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9326324, ECO:0000269|PubMed:9538513, ECO:0000269|PubMed:9973283}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombocytopenia 13, syndromic (THC13) [MIM:620776]: An autosomal recessive form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC13 patients have enlarged, gray platelets with defective function. Some affected individuals have leukopenia or anemia and pancytopenia. Additional variable features include mitral valve malformations, pyloric stenosis, and impaired intellectual development. {ECO:0000269|PubMed:30247636, ECO:0000269|PubMed:33510604, ECO:0000269|PubMed:34159722, ECO:0000269|PubMed:36395340}. The disease is caused by variants affecting the gene represented in this entry.

NA

P02649; P05067; Q96FN4; Q9BVJ7; O14732; Q13564; P54727; Q8TBC4; P61081

EC 6.2.1.-

3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; Ligase; Nucleotide-binding; Proteomics identification; Reference proteome; Ubl conjugation pathway

B,I

57143

508

0.08

45.25

5.82

-8.21

-9.09

NLRP3

Homo sapiens (Human)

PYRIN-containing APAF1-like protein 1; PYPAF1; NALP3; NACHT, LRR and PYD domains-containing protein 3; Cryopyrin; Cold-induced autoinflammatory syndrome 1 protein; CLR1.1; CIAS1; C1orf7; Angiotensin/v

NLRP family

NA

In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth. During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF. As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation.

Familial cold autoinflammatory syndrome 1 (FCAS1) [MIM:120100]: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:12522564, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:17284928, ECO:0000269|PubMed:24952504}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Muckle-Wells syndrome (MWS) [MIM:191900]: A hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs. {ECO:0000269|PubMed:11687797, ECO:0000269|PubMed:11992256, ECO:0000269|PubMed:12355493, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chronic infantile neurologic cutaneous and articular syndrome (CINCA) [MIM:607115]: Rare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation. {ECO:0000269|PubMed:12032915, ECO:0000269|PubMed:12483741, ECO:0000269|PubMed:14630794, ECO:0000269|PubMed:15231984, ECO:0000269|PubMed:15334500, ECO:0000269|PubMed:15593220, ECO:0000269|PubMed:24952504, ECO:0000269|PubMed:31086329}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Keratoendothelitis fugax hereditaria (KEFH) [MIM:148200]: An autosomal dominant corneal disease that periodically, and fleetingly, affects the corneal endothelium, stroma, and vision, eventually leading to central corneal stromal opacities in some patients. The disease is characterized by unilateral attacks of ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1-2 days but vision remains blurry for several weeks. The attacks start at the age of 3-12 years and can affect either eye. They generally decrease in frequency and get milder with age. {ECO:0000269|PubMed:29366613, ECO:0000269|PubMed:35559676}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 34, with or without inflammation (DFNA34) [MIM:617772]: A form of 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. DFNA34 is a postlingual, slowly progressive form with variable severity and variable additional features. Some DFNA34 patients have autoinflammatory manifestations. {ECO:0000269|PubMed:28847925}. The disease may be caused by variants affecting the gene represented in this entry.

NA

P27797; P36957; P19525; Q7Z434; Q8TDX7; Q96P20; Q9ULZ3; Q80H93; P0DTC9; Q9ES74; Q8TDX7-1

NA

3D-structure; Activator; ADP-ribosylation; Alternative splicing; Amyloidosis; ATP-binding; Cytoplasm; Cytoskeleton; Deafness; Disease variant; Disulfide bond; Endoplasmic reticulum; Golgi apparatus; Hydrolase; Immunity; Inflammasome; Inflammatory response; Innate immunity; Isopeptide bond; Leucine-rich repeat; Lipoprotein; Membrane; Mitochondrion; Non-syndromic deafness; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Secreted; Transcription; Transcription regulation; Ubl conjugation

A

115171

1010

0.08

45.92

6.17

-11.22

-9.21

KAT2B

Homo sapiens (Human)

Spermidine acetyltransferase KAT2B; PCAF; P300/CBP-associated factor; P/CAF; Lysine acetyltransferase 2B; Histone acetyltransferase PCAF; Histone acetylase PCAF

Acetyltransferase family, GCN5 subfamily

Acyltransferase

Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY, PLK4 and TBX5. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Also acetylates spermidine. Functions as a histone acetyltransferase (HAT) to promote transcriptional activation.

Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

DB08186; DB01992; DB08291

O60566; Q92793; Q96KQ7; Q09472; Q16665; Q9Y5W3; Q96EB6; Q8IXJ6; Q7Z699; Q16594; Q15672; P22415; P28033; P03129; P02299; P84040; P0DTC9; P59595; O88898-2; P03255; P03255-2

EC 2.3.1.48

3D-structure; Activator; Acyltransferase; Biological rhythms; Bromodomain; Cell cycle; Cytoplasm; Cytoskeleton; Disease variant; Host-virus interaction; Nucleus; Proteomics identification; Reference proteome; Transcription; Transcription regulation; Transferase

A

18743.8

162

0.12

25.09

9.44

9.34

-8.58

WNT7A

Homo sapiens (Human)

Protein Wnt-7a

Wnt family

NA

Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development. Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes. Required for normal neural stem cell proliferation in the hippocampus dentate gyrus. Required for normal progress through the cell cycle in neural progenitor cells, for self-renewal of neural stem cells, and for normal neuronal differentiation and maturation. Promotes formation of synapses via its interaction with FZD5. Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway.

Limb pelvis hypoplasia aplasia syndrome (LPHAS) [MIM:276820]: A syndrome of severe deficiency of the extremities due to hypo- or aplasia of one or more long bones of one or more limbs. Pelvic manifestations include hip dislocation, hypoplastic iliac bone and aplastic pubic bones. Thoracic deformity, unusual facies and genitourinary anomalies can be present. {ECO:0000269|PubMed:16826533, ECO:0000269|PubMed:17431918, ECO:0000269|PubMed:20949531, ECO:0000269|PubMed:21271649, ECO:0000269|PubMed:27638328}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fuhrmann syndrome (FUHRS) [MIM:228930]: Distinct limb-malformation disorder characterized also by various degrees of limb aplasia/hypoplasia and joint dysplasia. {ECO:0000269|PubMed:16826533}. The disease is caused by variants affecting the gene represented in this entry.

NA

P55212; P22607; P06396; P13473-2; Q9UMX0; Q9Y5W5; Q5T9L3; Q9Z0J1

NA

3D-structure; Developmental protein; Disease variant; Disulfide bond; Extracellular matrix; Glycoprotein; Lipoprotein; Proteomics identification; Reference proteome; Secreted; Signal; Wnt signaling pathway

A,B

40475.5

356

0.1

50.49

7.67

1.62

-8.42

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

-8.6

MAOA

Homo sapiens (Human)

Monoamine oxidase A; Amine oxidase [flavin-containing] A

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine. Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues.

Brunner syndrome (BRNRS) [MIM:300615]: A form of X-linked non-dysmorphic mild intellectual disability. Male patients are affected by borderline intellectual deficit and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior. {ECO:0000269|PubMed:8211186}. The disease is caused by variants affecting the gene represented in this entry.

DB01472; DB00918; DB00182; DB06698; DB04889; DB13876; DB01445; DB06774; DB00215; DB04017; DB09130; DB05205; DB07641; DB00988; DB01363; DB00668; DB12329; DB01175; DB03147; DB14914; DB00614; DB01381; DB07919; DB04818; DB01247; DB00601; DB01577; DB00805; DB01442; DB01171; DB08804; DB00952; DB04820; DB00184; DB04821; DB06412; DB01626; DB00780; DB00191; DB00388; DB00397; DB09244; DB04850; DB00721; DB01168; DB00571; DB00852; DB09363; DB00140; DB00953; DB06654; DB01037; DB01104; DB00669; DB14569; DB09042; DB00624; DB13943; DB13944; DB13946; DB09245; DB00752; DB15328; DB09185; DB04832; DB00315; DB00909

P27338

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Catecholamine metabolism; Direct protein sequencing; Disease variant; FAD; Flavoprotein; Intellectual disability; Membrane; Mitochondrion; Mitochondrion outer membrane; Neurotransmitter degradation; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A

58195.3

513

0.11

34.97

7.98

2.87

-9.77

PDE3A

Homo sapiens (Human)

cGMP-inhibited 3',5'-cyclic phosphodiesterase A; Phosphodiesterase 3A; Cyclic GMP-inhibited phosphodiesterase A; Cyclic GMP inhibited phosphodiesterase A; CGI-PDE A

Cyclic nucleotide phosphodiesterase family, PDE3 subfamily

Phosphoric diester hydrolase

Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

Hypertension and brachydactyly syndrome (HTNB) [MIM:112410]: A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. {ECO:0000269|PubMed:25961942}. The disease is caused by variants affecting the gene represented in this entry.

DB01223; DB01427; DB00261; DB00201; DB01166; DB04880; DB05266; DB00922; DB00235; DB01303; DB00277; DB08811; DB09283

Q9Y6D6; Q9Y6D5

EC 3.1.4.17

3D-structure; cAMP; cGMP; Cytoplasm; Direct protein sequencing; Disease variant; Hydrolase; Isopeptide bond; Manganese; Membrane; Metal-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation

A,B

108171

939

0.11

39.75

6.53

-4.15

-9.25

PNMT

Homo sapiens (Human)

PNMTase; PENT; Noradrenaline N-methyltransferase

Class I-like SAM-binding methyltransferase superfamily, NNMT/PNMT/TEMT family

NA

Converts noradrenaline to adrenaline.

A chromosomal aberration involving TRIM24/TIF1 is found in papillary thyroid carcinomas (PTCs). Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene. {ECO:0000269|PubMed:10439047}.

DB08129; DB08128; DB07739; DB07798; DB07747; DB03468; DB08550; DB03824; DB04273; DB07906; DB07597; DB09571; DB00968; DB08631; DB01752; DB08654

Q9P2G9-2; Q8TBB1

EC 2.1.1.28

3D-structure; Catecholamine biosynthesis; Direct protein sequencing; Methyltransferase; Phosphoprotein; Proteomics identification; Reference proteome; S-adenosyl-L-methionine; Transferase

A

29198.9

264

0.09

54.33

5.91

-3.69

-10

GNG2

Homo sapiens (Human)

NA

NA

G protein gamma family

Transferase / transferase inhibitor

G-protein beta-subunit binding.Signal transducer activity.

HDAC4 point mutations and chromosomal microdeletions encompassing this gene have been found in patients with brachydactyly and intellectual disability syndrome (PubMed:20691407, PubMed:23188045, PubMed:24715439). However, HDAC4 haploinsufficiency is not fully penetrant and multiple genes may contribute to manifestation of the full phenotypic spectrum (PubMed:23188045, PubMed:24715439). {ECO:0000269|PubMed:20691407, ECO:0000269|PubMed:23188045, ECO:0000269|PubMed:24715439}.; DISEASE: Neurodevelopmental disorder with central hypotonia and dysmorphic facies (NEDCHF) [MIM:619797]: An autosomal dominant disease characterized by global developmental delay, impaired intellectual development, seizures, distinctive facial features, scoliosis, delayed closure of the anterior fontanel, and non-specific brain abnormalities. {ECO:0000269|PubMed:33537682}. The disease is caused by variants affecting the gene represented in this entry.

DB01159

P62873

NA

3D-structure; Acetylation; Cell membrane; Host-virus interaction; Lipoprotein; Membrane; Methylation; Prenylation; Proteomics identification; Reference proteome; Transducer

G

37822.3

331

0.09

52.96

7.77

2.02

-8.49

TF

Homo sapiens (Human)

Siderophilin; Serotransferrin; PRO1400; Beta-1 metal-binding globulin

Transferrin family

Transferrin

It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.

Atransferrinemia (ATRAF) [MIM:209300]: A rare autosomal recessive disorder characterized by abnormal synthesis of transferrin leading to iron overload and microcytic hypochromic anemia. {ECO:0000269|PubMed:11110675, ECO:0000269|PubMed:15466165}. The disease is caused by variants affecting the gene represented in this entry.

DB01370; DB14517; DB14518; DB01294; DB14526; DB14527; DB11136; DB14528; DB14529; DB14530; DB00515; DB09130; DB11397; DB13949; DB14490; DB14491; DB14488; DB14501; DB14489; DB13257; DB06215; DB06784; DB05260; DB01592; DB00893; DB00677; DB06757; DB11182; DB14520; DB01593; DB14487; DB14533; DB14548

O43315; O00501; Q7Z7G2; Q9GZR5; Q9Y282; Q96KR6; P01350; P08034; Q8NBJ4; O15529; Q8TED1; Q7Z5P4; A8MZ59; O15173; Q96TC7; Q3KNW5; Q9BXS9-3; Q99523; O43278-2; Q8N9I0; P02786; Q4KMG9; Q9K0U9; Q09057; Q9K0V0; P02786

NA

3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Ion transport; Iron; Iron transport; Metal-binding; Methylation; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Secreted; Signal; Transport

A

35854.5

324

0.1

34.17

7.58

1.42

-9.14

S1PR2

Homo sapiens (Human)

Sphingosine 1-phosphate receptor Edg-5; S1PR2; S1P2; S1P receptor Edg-5; S1P receptor 2; Endothelial differentiation G-protein coupled receptor 5

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.

Deafness, autosomal recessive, 68 (DFNB68) [MIM:610419]: 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:26805784}. The disease is caused by variants affecting the gene represented in this entry.

NA

P16144; Q9JK11-1

NA

3D-structure; Cell membrane; Deafness; Disease variant; G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Non-syndromic deafness; Palmitate; Proteomics identification; Receptor; Reference proteome; Transducer; Transmembrane; Transmembrane helix

R

28917.3

264

0.11

38.95

9.11

9.27

-8.8

PDGFRA

Homo sapiens (Human)

RHEPDGFRA; Platelet-derived growth factor receptor 2; Platelet-derived growth factor alpha receptor; PDGFR2; PDGFR-alpha; PDGFR-2; PDGF-R-alpha; CD140a antigen; CD140a; CD140 antigen-like family membe

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

Kinase

Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.

A chromosomal aberration involving PDGFRA is found in some cases of hypereosinophilic syndrome. Interstitial chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-PDGFRA). Mutations that cause overexpression and/or constitutive activation of PDGFRA may be a cause of hypereosinophilic syndrome. {ECO:0000269|PubMed:12808148}.; DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:15928335}. The gene represented in this entry may be involved in disease pathogenesis. Mutations causing PDGFRA constitutive activation have been found in gastrointestinal stromal tumors lacking KIT mutations (PubMed:12522257). {ECO:0000269|PubMed:12522257}.; DISEASE: GIST-plus syndrome (GISTPS) [MIM:175510]: A disorder characterized by multiple mesenchymal tumors of the gastrointestinal tract, including gastrointestinal stromal tumor, inflammatory fibroid polyps, and fibroid tumors. Additional features are coarse facies and skin, broad hands and feet, and premature tooth loss. GISTPS is an autosomal dominant disease with incomplete penetrance. Gastrointestinal stromal tumor and inflammatory fibroid polyps may also occur in isolation. {ECO:0000269|PubMed:14699510, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:25975287}. The disease is caused by variants affecting the gene represented in this entry.

DB12742; DB00102; DB12147; DB10772; DB12010; DB00619; DB09078; DB06595; DB09079; DB06043; DB06589; DB08901; DB08896; DB14840; DB01268; DB11800; DB05146

P46108; P46109; P00533; Q8N6L0; P04085; P01127; Q9NRA1; P31947; P62258; Q9NRA1-1; A8T7D5; P05067; Q8IY26

EC 2.7.10.1

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cell projection; Chemotaxis; Developmental protein; Disease variant; Disulfide bond; Glycoprotein; Golgi apparatus; Host-virus interaction; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation

A

39294.8

345

0.11

46.74

6.6

-1.38

-8.42

TARS

Homo sapiens (Human)

NA

TARS

Class-II aminoacyl-tRNA synthetase family

Ligase / ligase inhibitor

ATP binding.Protein homodimerization activity.Threonine-tRNA ligase activity.TRNA binding.

Trichothiodystrophy 7, non-photosensitive (TTD7) [MIM:618546]: A form of trichothiodystrophy, a disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD7 patients do not manifest cutaneous photosensitivity. They have cysteine- and threonine-deficient hair with alternating light and dark 'tiger-tail' banding pattern observed under polarization microscopy. Inheritance pattern is autosomal recessive. {ECO:0000269|PubMed:31374204}. The disease is caused by variants affecting the gene represented in this entry.

DB00156

Q9BPX7; Q96CV9; O43704; A2RTX5

6.1.1.3

3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Disease variant; Ligase; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; Proteomics identification; Reference proteome; RNA-binding; tRNA-binding; Ubl conjugation

A,B

33945.3

290

0.13

41.57

6.29

-3.28

-8.45

UBA1

Homo sapiens (Human)

Ubiquitin-like modifier-activating enzyme 1; UBE1; Protein A1S9; A1S9T

Ubiquitin-activating E1 family

NA

Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.

Spinal muscular atrophy X-linked 2 (SMAX2) [MIM:301830]: A lethal infantile form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Clinical features include hypotonia, areflexia, and multiple congenital contractures. {ECO:0000269|PubMed:18179898, ECO:0000269|PubMed:23518311}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: VEXAS syndrome (VEXAS) [MIM:301054]: A sporadic, often fatal, treatment-refractory inflammatory syndrome that develops in late adulthood. Clinical features include fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. The disease affects only males and is associated with de novo somatic mutations. {ECO:0000269|PubMed:33108101}. The disease is caused by variants affecting the gene represented in this entry. Somatic variants affecting the initiator methionine of isoform 2 are recurrently found in VEXAS patients. These variants cause loss of isoform 2 and production of a shorter isoform with strongly reduced enzymatic activity from a downstream methionine (Met-67). {ECO:0000269|PubMed:33108101}.

DB04119; DB04216

Q9H2C0; P42858; Q96FW1; Q9BUZ4; P63279; O00308; Q76353

EC 6.2.1.45

3D-structure; Acetylation; Alternative initiation; ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant; Ligase; Mitochondrion; Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Ubl conjugation; Ubl conjugation pathway

A,B

119604

1068

0.09

36.15

5.4

-26.22

-8.36

ADORA2A

Homo sapiens (Human)

Adenosine receptor A2a; ADORA2; A2a Adenosine receptor; A(2A) adenosine receptor

G-protein coupled receptor 1 family

GPCR rhodopsin

The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Receptor for adenosine.

Intellectual developmental disorder, autosomal recessive 59 (MRT59) [MIM:617323]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26416544}. The disease is caused by variants affecting the gene represented in this entry.

DB08770; DB14132; DB00640; DB05009; DB05191; DB04853; DB00201; DB04932; DB09273; DB00651; DB00824; DB11757; DB17080; DB00555; DB00358; DB00683; DB01303; DB00806; DB06213; DB01412; DB00277

P30542; P29274; P29275; O15155; P21554; Q99418; O15354; Q7Z6G3; O43759-2; Q13107; Q5T9L3-1; P31424-1

NA

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

A

32419.4

296

0.12

39.04

8.77

7.19

-8.72

PTGDR2

Homo sapiens (Human)

PTGDR2; Chemoattractant receptor-homologous molecule expressed on Th2 cells; CD294

G-protein coupled receptor 1 family

GPCR rhodopsin

Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin- sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, ADRBK1/GRK2, GPRK5/GRK5 and GRK6. Receptoractivation is responsible, at least in part, in immune regulation and allergic/inflammation responses.

Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA) [MIM:618922]: An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, hypotonia, severe to profound intellectual disability, early-onset epilepsy, and microcephaly. Neuroimaging shows cerebral atrophy, thin corpus callosum and hypomyelination in a majority of cases. Death in childhood may occur. {ECO:0000269|PubMed:27435318, ECO:0000269|PubMed:28097321, ECO:0000269|PubMed:32286009, ECO:0000269|PubMed:33476302, ECO:0000269|PubMed:33500274}. The disease is caused by variants affecting the gene represented in this entry.

DB00770; DB12789; DB00917; DB01088; DB00328; DB02056; DB13036; DB00605; DB04828

NA

NA

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

A

49740.6

447

0.1

37.89

10.13

21.88

-9.07