TNKS2

Homo sapiens (Human)

Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribos

ARTD/PARP family

Glycosyltransferases

Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.

Intellectual developmental disorder with macrocephaly, seizures, and speech delay (IDDMSSD) [MIM:618158]: An autosomal dominant neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures. {ECO:0000269|PubMed:30290153}. The disease is caused by variants affecting the gene represented in this entry.

NA

O15084; Q7Z6K5-1; O15169; Q9NWV8; P11274; Q13698; Q9NRI5; Q6V0I7; Q9NWT6; P14652; Q9UIQ6; Q14980; Q9BZL4; Q92698; P78314; O43815; P54274; Q9C0C2; Q9UHP3; Q06649

EC 2.4.2.30

3D-structure; ADP-ribosylation; ANK repeat; Chromosome; Cytoplasm; Glycosyltransferase; Golgi apparatus; Hydroxylation; Membrane; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; Proteomics identification; Reference proteome; Repeat; Telomere; Transferase; Ubl conjugation; Wnt signaling pathway; Zinc

A

23695.5

208

0.11

47.61

8.28

2.88

-8.22

TDO2

Homo sapiens (Human)

Tryptophanase; Tryptophan pyrrolase; Tryptophan oxygenase; Tryptamin 2,3-dioxygenase; TRPO; TO

Tryptophan 2,3-dioxygenase family

Oxygenase

Catalyzes the oxidative cleavage of the indole moiety. Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine.

Hypertryptophanemia (HYPTRP) [MIM:600627]: An autosomal recessive condition characterized by persistent hypertryptophanemia and hyperserotoninemia. {ECO:0000269|PubMed:28285122}. The disease is caused by variants affecting the gene represented in this entry.

DB00779; DB00500; DB00150

O43865; O95671; P27797; P12830; P36957; O60762; P06730; Q8TBB1; Q9H8S9; Q70IA8; Q8TDX7; Q9NPG2; Q9HAN9; P20393; Q9NRD5; Q8IYS1; O00560; Q9H190; P48775; Q68DK2-5

EC 1.13.11.11

3D-structure; Dioxygenase; Disease variant; Heme; Iron; Metal-binding; Oxidoreductase; Proteomics identification; Reference proteome; Tryptophan catabolism

A,B

83454.8

701

0.11

43.93

6.93

-0.48

-8.21

THRB

Homo sapiens (Human)

c-erbA-beta; c-erbA-2; THR1; Nuclear receptor subfamily 1 group A member 2; NR1A2; ERBA2

Nuclear hormone receptor family, NR1 subfamily

Nuclear hormone receptor

High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Nuclear hormone receptor that can act as a repressor or activator of transcription.

Thyroid hormone resistance, generalized, autosomal dominant (GRTHD) [MIM:188570]: An autosomal dominant disease characterized by high levels of circulating thyroid hormones (T3-T4), goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Patients have normal or slightly elevated thyroid stimulating hormone (TSH). {ECO:0000269|PubMed:10660344, ECO:0000269|PubMed:12511610, ECO:0000269|PubMed:12554782, ECO:0000269|PubMed:1314846, ECO:0000269|PubMed:1324420, ECO:0000269|PubMed:1563081, ECO:0000269|PubMed:1587388, ECO:0000269|PubMed:1619012, ECO:0000269|PubMed:1661299, ECO:0000269|PubMed:16804041, ECO:0000269|PubMed:1846005, ECO:0000269|PubMed:19268523, ECO:0000269|PubMed:2153155, ECO:0000269|PubMed:2510172, ECO:0000269|PubMed:7833659, ECO:0000269|PubMed:8175986, ECO:0000269|PubMed:8514853, ECO:0000269|PubMed:8664910, ECO:0000269|PubMed:8889584}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thyroid hormone resistance, generalized, autosomal recessive (GRTHR) [MIM:274300]: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone. {ECO:0000269|PubMed:1653889}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. {ECO:0000269|PubMed:7528740, ECO:0000269|PubMed:8381821}. The disease is caused by variants affecting the gene represented in this entry.

DB08085; DB03181; DB02106; DB01118; DB00509; DB05035; DB03788; DB03176; DB00451; DB00279; DB01583; DB05192; DB07425; DB09100; DB03604

Q60974; Q9Y618

NA

3D-structure; Alternative splicing; Deafness; Disease variant; DNA-binding; Metal-binding; Nucleus; Proteomics identification; Receptor; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger

A,B

27235.4

239

0.09

43.29

5.42

-8.55

-8.19

CYP1A2

Homo sapiens (Human)

NA

NA

Cytochrome P450 family

Oxidoreductase

Aromatase activity.Caffeine oxidase activity.Demethylase activity.Electron carrier activity.Enzyme binding.Heme binding.Iron ion binding.Monooxygenase activity.Oxidoreductase activity.Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen.Oxygen binding.

Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. The disease is caused by variants affecting the gene represented in this entry.

DB08496; DB01667; DB14132; DB04356; DB02489; DB11932; DB12001; DB05812; DB13573; DB01418; DB00316; DB15568; DB06594; DB00518; DB05396; DB00969; DB07453; DB01424; DB01223; DB01118; DB00321; DB00261; DB01217; DB01435; DB06605; DB05676; DB06413; DB06216; DB01072; DB15011; DB06442; DB06626; DB00993; DB00972; DB13203; DB05015; DB16703; DB06769; DB01086; DB06770; DB06771; DB06732; DB00195; DB04889; DB11967; DB13975; DB00188; DB12151; DB01558; DB14018; DB13812; DB00201; DB09061; DB14737; DB11791; DB06774; DB00564; DB06016; DB01136; DB12814; DB00477; DB00356; DB01166; DB00501; DB01012; DB00568; DB00827; DB00537; DB00215; DB12499; DB14025; DB00349; DB01242; DB00575; DB00758; DB00363; DB00286; DB11672; DB14635; DB00924; DB08912; DB00851; DB06292; DB01254; DB01609; DB01151; DB16650; DB12161; DB01191; DB00633; DB11994; DB00586; DB11511; DB12945; DB00280; DB01184; DB09167; DB05928; DB01142; DB09273; DB00470; DB00476; DB00625; DB15444; DB06210; DB13874; DB11718; DB00467; DB11404; DB00530; DB00783; DB13952; DB13953; DB13954; DB13955; DB13956; DB00655; DB04574; DB13592; DB00330; DB00898; DB00977; DB00773; DB01628; DB00927; DB04854; DB01482; DB00574; DB12265; DB15669; DB01195; DB08972; DB04841; DB00544; DB00472; DB00499; DB00176; DB01320; DB00998; DB14029; DB06160; DB01044; DB01241; DB01155; DB01645; DB01381; DB00986; DB00365; DB00400; DB05708; DB00629; DB00502; DB01094; DB14999; DB04076; DB11737; DB00619; DB00458; DB11564; DB01306; DB09456; DB09564; DB01307; DB00047; DB01309; DB00030; DB00046; DB11567; DB00071; DB11568; DB05258; DB00034; DB00105; DB15131; DB00011; DB00018; DB00069; DB00060; DB00068; DB00033; DB00951; DB11757; DB09570; DB01026; DB01097; DB16217; DB09078; DB01002; DB05667; DB00281; DB12406; DB09198; DB04948; DB00978; DB06448; DB16220; DB01601; DB00455; DB04871; DB06077; DB01283; DB00772; DB00934; DB06234; DB14009; DB00784; DB01065; DB00170; DB00454; DB00532; DB00333; DB00763; DB00553; DB01028; DB09241; DB01233; DB00379; DB06148; DB01388; DB06595; DB00370; DB16236; DB00745; DB11763; DB00218; DB06510; DB14011; DB00461; DB00607; DB00779; DB00788; DB06600; DB00238; DB06803; DB00184; DB01115; DB11793; DB00435; DB05115; DB00717; DB01059; DB00540; DB05990; DB01165; DB00334; DB16267; DB00338; DB00904; DB11632; DB11443; DB01173; DB11837; DB09330; DB01303; DB11697; DB00377; DB00715; DB06589; DB11774; DB00487; DB00008; DB00022; DB09122; DB13634; DB00806; DB11198; DB08883; DB00850; DB03783; DB01174; DB00388; DB00252; DB11450; DB01100; DB13823; DB04951; DB17472; DB11642; DB08910; DB15822; DB01058; DB01087; DB00794; DB00420; DB09288; DB01182; DB06479; DB00818; DB00571; DB13449; DB11892; DB04216; DB00908; DB00468; DB01129; DB00980; DB09290; DB00863; DB01367; DB00409; DB02709; DB13174; DB01045; DB11753; DB00740; DB14924; DB00503; DB00533; DB01656; DB15119; DB00268; DB00296; DB00412; DB00817; DB12332; DB13772; DB06654; DB11491; DB00418; DB01037; DB11689; DB06290; DB13261; DB15093; DB00052; DB00398; DB01208; DB09118; DB00428; DB06820; DB00382; DB00675; DB06083; DB09071; DB05488; DB09256; DB01079; DB01405; DB00857; DB08880; DB11712; DB01412; DB00277; DB00730; DB01623; DB00208; DB06137; DB00697; DB01056; DB06264; DB00752; DB00384; DB12245; DB00831; DB15442; DB00440; DB00685; DB08867; DB14989; DB13609; DB06235; DB00313; DB08881; DB00661; DB09185; DB12026; DB00682; DB02134; DB00549; DB00744; DB00315; DB00425; DB09225; DB09120

O95870

1.14.14.1; 4.2.1.152

3D-structure; Direct protein sequencing; Endoplasmic reticulum; Fatty acid metabolism; Glycoprotein; Heme; Iron; Lipid metabolism; Lyase; Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Steroid metabolism; Sterol metabolism

A

54475

480

0.1

40.43

9.16

9.89

-8.2

OXCT1

Homo sapiens (Human)

NA

OXCT;SCOT

3-oxoacid CoA-transferase family

Transferase

3-oxoacid CoA-transferase activity.Protein homodimerization activity.

Succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOTD) [MIM:245050]: A disorder of ketone body metabolism, characterized by episodic ketoacidosis. Patients are usually asymptomatic between episodes. {ECO:0000269|PubMed:10964512, ECO:0000269|PubMed:21296660, ECO:0000269|PubMed:31073471, ECO:0000269|PubMed:33596448, ECO:0000269|PubMed:9671268}. The disease is caused by variants affecting the gene represented in this entry.

DB02731; DB00139

NA

2.8.3.5

3D-structure; Alternative splicing; Direct protein sequencing; Disease variant; Lipid metabolism; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Transit peptide

A,B,C,D

49904.1

459

0.07

28.89

7.05

0.12

-8.2

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

-8.2

KCNN2

Homo sapiens (Human)

Small conductance calcium-activated potassium channel protein 2; SKCa2; SKCa 2; SK2; KCa2.2

Potassium channel KCNN family, KCa2.2/KCNN2 subfamily

Voltage-gated ion channel

Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.

Dystonia 34, myoclonic (DYT34) [MIM:619724]: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT34 is an autosomal dominant form characterized by childhood-onset dystonia predominantly affecting hands and neck, with a fast tremor with superimposed myoclonus and, in some individuals, subtle cerebellar signs. {ECO:0000269|PubMed:32212350}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without variable movement or behavioral abnormalities (NEDMAB) [MIM:619725]: An autosomal dominant disorder characterized by motor and language developmental delay, intellectual disability often associated with early-onset movement disorders comprising cerebellar ataxia and/or extrapyramidal symptoms. Other variable features include autism spectrum disorder or autistic features and epilepsy. {ECO:0000269|PubMed:33242881}. The disease is caused by variants affecting the gene represented in this entry.

DB02587; DB01110; DB01054; DB00721; DB16733; DB00867; DB09089

P35609

NA

3D-structure; Alternative splicing; Calmodulin-binding; Cytoplasm; Disease variant; Dystonia; Intellectual disability; Ion channel; Ion transport; Membrane; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

B,R

26727.8

233

0.06

24.91

5.01

-11.73

-8.19

acrB

Escherichia coli (strain K12)

NA

b0462;acrE;JW0451

Resistance-nodulation-cell division (RND) (TC 2.A.6) family

Transport protein

Drug:proton antiporter activity.Drug transmembrane transporter activity.Identical protein binding.

Pyruvate kinase hyperactivity (PKHYP) [MIM:102900]: Autosomal dominant phenotype characterized by increase of red blood cell ATP. {ECO:0000269|PubMed:9090535}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pyruvate kinase deficiency of red cells (PKRD) [MIM:266200]: A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. {ECO:0000269|PubMed:10087985, ECO:0000269|PubMed:10772876, ECO:0000269|PubMed:11328279, ECO:0000269|PubMed:11960989, ECO:0000269|PubMed:1536957, ECO:0000269|PubMed:1896471, ECO:0000269|PubMed:19085939, ECO:0000269|PubMed:2018831, ECO:0000269|PubMed:21794208, ECO:0000269|PubMed:7706479, ECO:0000269|PubMed:8161798, ECO:0000269|PubMed:8180378, ECO:0000269|PubMed:8476433, ECO:0000269|PubMed:8481523, ECO:0000269|PubMed:8483951, ECO:0000269|PubMed:8664896, ECO:0000269|PubMed:8807089, ECO:0000269|PubMed:9075576, ECO:0000269|PubMed:9482576, ECO:0000269|PubMed:9827908, ECO:0000269|PubMed:9886305, ECO:0000269|Ref.24}. The disease is caused by variants affecting the gene represented in this entry.

DB03619; DB04209; DB03825

P31224; P0AAW9; P0ADZ7

NA

3D-structure; Cell inner membrane; Cell membrane; Membrane; Reference proteome; Transmembrane; Transmembrane helix; Transport

A,B,C

60242.4

553

0.08

29.1

4.76

-18.86

-8.18

EIF2AK3

Homo sapiens (Human)

PEK

Protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily

Kinase

Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function. Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability.

Wolcott-Rallison syndrome (WRS) [MIM:226980]: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, intellectual disability and cardiovascular abnormalities. {ECO:0000269|PubMed:10932183, ECO:0000269|PubMed:12086964, ECO:0000269|PubMed:12960215, ECO:0000269|PubMed:16813601, ECO:0000269|PubMed:24168455, ECO:0000269|PubMed:24194294, ECO:0000269|PubMed:27145240, ECO:0000269|PubMed:28220546, ECO:0000269|PubMed:30906465, ECO:0000269|PubMed:30922274, ECO:0000269|PubMed:32216767, ECO:0000269|PubMed:34123975}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9NZJ5; P11021

EC 2.7.11.1

3D-structure; ADP-ribosylation; ATP-binding; Diabetes mellitus; Disease variant; Endoplasmic reticulum; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Signal; Stress response; Transferase; Translation regulation; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Unfolded protein response

A

29033.5

248

0.1

43.71

7.75

1.27

-8.19

phr

Synechococcus sp. (strain ATCC 27144 / PCC 6301 / SAUG 1402/1) (Anacystis nidulans)

NA

phrA;syc1392_c

DNA photolyase class-1 family

Lyase

Deoxyribodipyrimidine photo-lyase activity.DNA binding.Nucleotide binding.

Myeloperoxidase deficiency (MPOD) [MIM:254600]: A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. {ECO:0000269|PubMed:37198333, ECO:0000269|PubMed:7904599, ECO:0000269|PubMed:8142659, ECO:0000269|PubMed:8621627, ECO:0000269|PubMed:9354683, ECO:0000269|PubMed:9637725}. The disease is caused by variants affecting the gene represented in this entry.

DB03147

NA

4.1.99.3

3D-structure; Chromophore; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; FAD; Flavoprotein; Lyase; Nucleotide-binding

A

53346.9

473

0.1

53.22

6.92

-0.23

-8.16

MAOB

Homo sapiens (Human)

MAO-B; Amine oxidase [flavin-containing] B

Flavin monoamine oxidase family

CH-NH(2) donor oxidoreductase

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. MAOB preferentially degrades benzylamine and phenylethylamine.

Microvascular complications of diabetes 5 (MVCD5) [MIM:612633]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Homozygosity for the Leu-55 allele is strongly associated with the development of retinal disease in diabetic patients.

DB08176; DB02211; DB08516; DB08480; DB01472; DB04307; DB07512; DB07513; DB00915; DB00182; DB06698; DB04889; DB00215; DB09130; DB04147; DB00988; DB01363; DB00668; DB01175; DB02509; DB03147; DB14914; DB00614; DB04818; DB02095; DB01247; DB00601; DB01577; DB01442; DB01171; DB08082; DB02643; DB04677; DB03894; DB08804; DB04820; DB00184; DB04821; DB12612; DB01626; DB00780; DB00191; DB00388; DB01132; DB00721; DB01168; DB01367; DB09363; DB06654; DB01037; DB01104; DB14569; DB09042; DB00752; DB16446; DB09185; DB04832; DB00909

P55212; P28329-3; Q8NI60; Q5RI15; Q92915-2; P22607; Q53GS7; P06396; P01112; O14901; P13473-2; P21397; Q9BVL2; O75400-2; P62826; Q6NTF9-3; Q9Y371; Q7Z699; Q9UMX0; Q9Y649

EC 1.4.3.4

3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; FAD; Flavoprotein; Membrane; Mitochondrion; Mitochondrion outer membrane; Oxidoreductase; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix

A,B

56019.9

494

0.09

34.81

6.51

-2.2

-8.18

MGLL

Homo sapiens (Human)

Monoacylglycerol lipase; MGL; Lysophospholipaselike; Lysophospholipase-like; Lysophospholipase homolog; HUK5; HU-K5

AB hydrolase superfamily, Monoacylglycerol lipase family

Carboxylic ester hydrolase

Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain. Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth. Converts monoacylglycerides to free fatty acids and glycerol.

Systemic lupus erythematosus 9 (SLEB9) [MIM:610927]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17360460}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency, common variable, 7 (CVID7) [MIM:614699]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. {ECO:0000269|PubMed:22035880}. The disease is caused by variants affecting the gene represented in this entry.

NA

P07550; P37235

EC 3.1.1.23

3D-structure; Alternative splicing; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Lipid biosynthesis; Lipid degradation; Lipid metabolism; Membrane; Nitration; Phosphoprotein; Proteomics identification; Reference proteome; Serine esterase

A

31808.4

289

0.08

29.7

6.73

-0.91

-8.17

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

-8.18

CHRNB4

Homo sapiens (Human)

CHRNB4; Beta-4 nAChR

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

Neurotransmitter receptor

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

Renal cell carcinoma (RCC) [MIM:144700]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype. {ECO:0000269|PubMed:20054297, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}. The disease may be caused by variants affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682). {ECO:0000269|PubMed:23792563, ECO:0000269|PubMed:25728682}.; DISEASE: Luscan-Lumish syndrome (LLS) [MIM:616831]: An autosomal dominant syndrome with a variable phenotype. Clinical features include macrocephaly, distinctive facial appearance, postnatal overgrowth, various degrees of learning difficulties, autism spectrum disorder, and intellectual disability. {ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:24852293, ECO:0000269|PubMed:26084711, ECO:0000269|PubMed:27317772}. The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, acute lymphoblastic (ALL) [MIM:613065]: A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. {ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24662245}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:16314571, ECO:0000269|PubMed:24509477}. The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.; DISEASE: Intellectual developmental disorder, autosomal dominant 70 (MRD70) [MIM:620157]: An autosomal dominant disorder characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rabin-Pappas syndrome (RAPAS) [MIM:620155]: An autosomal dominant neurodevelopmental disorder characterized by severely impaired global development, intellectual disability, microcephaly, facial dysmorphism, and variable congenital anomalies affecting the skeletal, genitourinary, cardiac, and other organ systems. {ECO:0000269|PubMed:32710489}. The disease is caused by variants affecting the gene represented in this entry.

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

Q6FHY5

NA

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

A,B

89661.2

775

0.12

35.11

6.07

-5.67

-8.17

CHRNA3-CHRNB4

Homo sapiens (Human)

Neuronal acetylcholine receptor

Ligand-gated ion channel (TC 1.A.9) family, Acetylcholine receptor (TC 1.A.9.1) subfamily, Alpha-3/CHRNA3 sub-subfamily

Neurotransmitter receptor

A type of nicotinic acetylcholine receptor, consisting of 3 and 4 subunits.

Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT (BAIPRCK) [MIM:191800]: An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. Additional autonomic features are impaired pupillary reflex and orthostatic hypotension. The disease manifests in utero or early childhood. {ECO:0000269|PubMed:31708116}. The disease is caused by variants affecting the gene represented in this entry.

DB00915; DB01156; DB00237; DB00565; DB09028; DB00514; DB07720; DB00898; DB00472; DB05710; DB01227; DB00848; DB00333; DB00184; DB01090; DB00202; DB01273

NA

NA

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

A,B

89661.2

775

0.12

35.11

6.07

-5.67

-8.17

PRKG1

Homo sapiens (Human)

cGMP-dependent protein kinase I; cGMP-dependent protein kinase 1; cGKI; cGK1; cGK 1; PRKGR1B; PRKGR1A; PRKG1B

Protein kinase superfamily, AGC Ser/Thr protein kinase family, cGMP subfamily

Kinase

GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates MRVI1/IRAG and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway.

Aortic aneurysm, familial thoracic 8 (AAT8) [MIM:615436]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:23910461}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q13873; Q86V42; P25791; O76074; O15015; O94989; P25791-3; Q6FHY5; Q13976-2; Q9NYW8

EC 2.7.11.12

3D-structure; Acetylation; Allosteric enzyme; Alternative splicing; Aortic aneurysm; ATP-binding; cGMP; cGMP-binding; Coiled coil; Cytoplasm; Disease variant; Disulfide bond; Kinase; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Serine/threonine-protein kinase; Transferase

C

38032

335

0.12

38.26

6.23

-2.54

-8.16

CHRM1

Homo sapiens (Human)

M1 receptor

G-protein coupled receptor 1 family, Muscarinic acetylcholine receptor subfamily, CHRM1 sub-subfamily

GPCR rhodopsin

Primary transducing effect is Pi turnover. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.

Pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:15138885}. The disease is caused by variants affecting the gene represented in this entry.

DB03128; DB08897; DB05752; DB00321; DB00543; DB00517; DB04365; DB01238; DB14185; DB00572; DB00245; DB00767; DB01019; DB00810; DB09128; DB00835; DB00354; DB00411; DB00185; DB00477; DB01239; DB00568; DB00771; DB00363; DB00907; DB00979; DB00942; DB00434; DB00496; DB01151; DB00804; DB01231; DB00280; DB09167; DB01142; DB00366; DB01175; DB09194; DB06702; DB01148; DB00875; DB00483; DB00986; DB06787; DB11181; DB00725; DB00424; DB09262; DB00458; DB00332; DB01221; DB00408; DB00934; DB04843; DB00454; DB06709; DB00940; DB01403; DB00462; DB00340; DB01233; DB00805; DB01618; DB05152; DB00622; DB05766; DB00540; DB00334; DB01062; DB00383; DB00219; DB00715; DB01085; DB00670; DB06153; DB00387; DB00392; DB00420; DB01069; DB00782; DB00777; DB12278; DB11156; DB01224; DB11855; DB13581; DB00747; DB01591; DB02010; DB00342; DB11235; DB01409; DB01036; DB00193; DB00505; DB00508; DB00376; DB09089; DB00726; DB00809; DB00209; DB09076; DB09185; DB00246

NA

NA

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

A

33337

291

0.15

26.7

8.75

5.76

-8.16

RXRB

Homo sapiens (Human)

Retinoid X receptor beta; Nuclear receptor subfamily 2 group B member 2; NR2B2

Nuclear hormone receptor family, NR2 subfamily

Nuclear hormone receptor

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). Receptor for retinoic acid.

Noonan syndrome 13 (NS13) [MIM:619087]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells. NS13 inheritance is autosomal dominant. There is considerable variability in severity. {ECO:0000269|PubMed:32721402}. The disease is caused by variants affecting the gene represented in this entry.

DB08175; DB00459; DB00210; DB00523; DB00307; DB01393; DB03756; DB00926; DB01941; DB07929; DB02746; DB00412; DB00799; DB07080; DB00755

Q00975; Q9HB07; F1D8P7; Q13133; Q13133-3; Q96RI1-1; P04150; Q9NRD5; P37231; P10276; P10276-2; P10826-2; P13631; Q6IQ16; Q13137; Q96B26; Q08379; Q6A162; Q9UJV3-2; Q13133-3; Q96RI1-1; O43586; P10276; P10826-2; Q8IUQ4-2; O75528; Q12800; Q9UBB9; Q05BL1; P14373; O94972; Q96S82

NA

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

A,C

28845.8

251

0.08

54.86

6.74

-0.6

-8.15

CYCS

Homo sapiens (Human)

NA

CYC

Cytochrome c family

Oxidoreductase

Electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity.Heme binding.Metal ion binding.

Thrombocytopenia 4 (THC4) [MIM:612004]: A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:18345000}. The disease is caused by variants affecting the gene represented in this entry.

DB11638; DB03317; DB03366; DB01017; DB02110; DB03977; DB03934; DB04249

O14727; P05067; Q6XD76; Q9NSI6-4; Q3SXR2; Q96BR5; Q9UKG9-2; O00303; Q8IZU1; Q3SYB3; P06241; Q8N5Z5; Q6A162; Q1L5Z9; P02750; Q8IYG6; Q6FHY5; A0A0A0MR05; Q9BUL5; Q6ZMI0-5; Q66K80; Q9NTN9-3; P37840; Q13573; Q92797-2; O43829; Q9FKS5

NA

3D-structure; Acetylation; Apoptosis; Direct protein sequencing; Disease variant; Electron transport; Heme; Iron; Metal-binding; Mitochondrion; Phosphoprotein; Proteomics identification; Reference proteome; Respiratory chain; Transport

A,B,C,D

11601.4

104

0.09

12.21

9.61

9.01

-8.16

PDK1

Homo sapiens (Human)

Pyruvate dehydrogenase kinase isoform 1; Pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial; PDHK1; PDH kinase 1

PDK/BCKDK protein kinase family

Kinase

Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.

TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma.; DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Li-Fraumeni syndrome (LFS) [MIM:151623]: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269|PubMed:10484981, ECO:0000269|PubMed:1565144, ECO:0000269|PubMed:1737852, ECO:0000269|PubMed:1933902, ECO:0000269|PubMed:1978757, ECO:0000269|PubMed:2259385, ECO:0000269|PubMed:36108750, ECO:0000269|PubMed:7887414, ECO:0000269|PubMed:8825920, ECO:0000269|PubMed:9452042}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Papilloma of choroid plexus (CPP) [MIM:260500]: A benign tumor of neuroectodermal origin that generally occurs in childhood, but has also been reported in adults. Although generally found within the ventricular system, choroid plexus papillomas can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. Patients present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures. {ECO:0000269|PubMed:12085209}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Adrenocortical carcinoma (ADCC) [MIM:202300]: A malignant neoplasm of the adrenal cortex and a rare childhood tumor. It occurs with increased frequency in patients with Beckwith-Wiedemann syndrome and Li-Fraumeni syndrome. {ECO:0000269|PubMed:11481490}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Basal cell carcinoma 7 (BCC7) [MIM:614740]: A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter. {ECO:0000269|PubMed:21946351}. Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Bone marrow failure syndrome 5 (BMFS5) [MIM:618165]: A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS5 is an autosomal dominant form characterized by infantile onset of severe red cell anemia requiring transfusion. Additional features include hypogammaglobulinemia, poor growth with microcephaly, developmental delay, and seizures. {ECO:0000269|PubMed:30146126}. The disease is caused by variants affecting the gene represented in this entry.

DB07403; DB08809

P05067; P08559; Q16513; P31749-1; P31751-1

EC 2.7.11.2

3D-structure; Alternative splicing; ATP-binding; Kinase; Mitochondrion; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Transferase; Transit peptide

A

42249.9

368

0.11

49.91

6.83

-0.46

-8.16