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

-6.95

HPD

Arabidopsis thaliana (Mouse-ear cress)

NA

At1g06570;PDS1;F12K11.9

4HPPD family

NA

Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism. {ECO:0000269|PubMed:15301540}."

Intellectual developmental disorder, autosomal dominant 62 (MRD62) [MIM:618793]: An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD62 is characterized by mild to moderately impaired intellectual development. {ECO:0000269|PubMed:27479843, ECO:0000269|PubMed:29460436}. The disease is caused by variants affecting the gene represented in this entry.

NA

P93836

1.13.11.27

3D-structure; Alternative splicing; Cytoplasm; Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phenylalanine catabolism; Reference proteome; Repeat; Tyrosine catabolism

B

41240.4

371

0.11

47.03

6.09

-4.66

-6.81

vatD

Enterococcus faecium (Streptococcus faecium)

NA

satA

Transferase hexapeptide repeat family

Transferase

Transferase activity, transferring acyl groups.

Cerebral creatine deficiency syndrome 3 (CCDS3) [MIM:612718]: An autosomal recessive disorder characterized by developmental delay/regression, intellectual disability, severe disturbance of expressive and cognitive speech, and severe depletion of creatine/phosphocreatine in the brain. Most patients develop a myopathy characterized by muscle weakness and atrophy later in life. {ECO:0000269|PubMed:11555793, ECO:0000269|PubMed:20682460, ECO:0000269|PubMed:22386973, ECO:0000269|PubMed:23660394, ECO:0000269|PubMed:23770102, ECO:0000269|PubMed:26490222, ECO:0000269|PubMed:27233232}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Fanconi renotubular syndrome 1 (FRTS1) [MIM:134600]: A form of Fanconi renotubular syndrome, a disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. FRTS1 inheritance is autosomal dominant. {ECO:0000269|PubMed:29654216}. The disease is caused by variants affecting the gene represented in this entry.

DB01992; DB01764; DB01669

NA

2.3.1.-

3D-structure; Acyltransferase; Antibiotic resistance; Repeat; Transferase

A,B,C,D,E,F

68559.3

609

0.09

29.65

5.39

-11.69

-6.78

IL3RA

Homo sapiens (Human)

Interleukin-3 receptor subunit alpha; IL3R; IL-3RA; IL-3R-alpha; IL-3R subunit alpha; IL-3 receptor subunit alpha; CD123 antigen; CD123

Type I cytokine receptor family, Type 5 subfamily

Cytokine receptor

This is a receptor for interleukin-3.

Microcephaly and chorioretinopathy, autosomal recessive, 2 (MCCRP2) [MIM:616171]: A severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities. {ECO:0000269|PubMed:25344692}. The disease is caused by variants affecting the gene represented in this entry.

DB00020; DB14731

O95393; O14523; Q8N6F1-2; P54852; Q8WWP7; Q8N5M9; Q92993; Q8TAP4-4; Q9NZG7; Q9NXK6; P17252; Q9Y6X1; Q15047-2; Q0VAQ4; Q8N2H4; Q5BJH2-2; Q9BVK8; Q8TBM7; Q6PI78; A5PKU2; O95183; P61981; P08700

NA

3D-structure; Alternative splicing; Disulfide bond; Glycoprotein; Membrane; Proteomics identification; Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix; Ubl conjugation

G

29237

253

0.12

46.45

9.01

8.21

-5.99

dacC

Escherichia coli (strain K12)

NA

b0839;JW0823

Peptidase S11 family

Hydrolase

Carboxypeptidase activity.Endopeptidase activity.Penicillin binding.Serine-type D-Ala-D-Ala carboxypeptidase activity.

Charcot-Marie-Tooth disease, axonal, 2T (CMT2T) [MIM:617017]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:26991897, ECO:0000269|PubMed:27588448}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:27583304}. The disease is caused by variants affecting the gene represented in this entry.

DB01602; DB00578; DB09319; DB00671; DB00274; DB01329; DB01331; DB00430; DB01332; DB09050; DB01000; DB00303

NA

3.4.16.4

3D-structure; Carboxypeptidase; Cell inner membrane; Cell membrane; Cell shape; Cell wall biogenesis/degradation; Direct protein sequencing; Hydrolase; Membrane; Peptidoglycan synthesis; Protease; Reference proteome; Signal

A,B,C,D

22829.7

214

0.07

21.24

6.36

-0.93

-6.39

HCN4

Homo sapiens (Human)

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Potassium channel HCN family

Voltage-gated ion channel

Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli. Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions.

Sick sinus syndrome 2 (SSS2) [MIM:163800]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth. {ECO:0000269|PubMed:15123648, ECO:0000269|PubMed:16407510, ECO:0000269|PubMed:20662977, ECO:0000269|PubMed:23103389}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Brugada syndrome 8 (BRGDA8) [MIM:613123]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:19165230}. The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Epilepsy, idiopathic generalized 18 (EIG18) [MIM:619521]: An autosomal dominant 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. EIG18 is characterized by onset of myoclonic seizures in infancy. Although the seizures remit, some patients may have later speech or cognitive impairment. {ECO:0000269|PubMed:30127718}. Disease susceptibility is associated with variants affecting the gene represented in this entry.

NA

O60741; Q9Y3Q4

NA

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

A

23211.2

197

0.12

42.69

8.67

3.11

-6.9

IMPDH1

Homo sapiens (Human)

Superoxide-inducible protein 12; SOI12; Probable inosine-5'-monophosphate dehydrogenase IMD1; NAD-dependent inosine monophosphate dehydrogenase; Inosine dehydrogenase; IMPDH-I; IMPDH 1; IMPDH; IMPD1;

IMPDH/GMPR family

CH-OH donor oxidoreductase

Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors. Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.

Retinitis pigmentosa 10 (RP10) [MIM:180105]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:11875049, ECO:0000269|PubMed:11875050, ECO:0000269|PubMed:16384941}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 11 (LCA11) [MIM:613837]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:16384941}. The disease is caused by variants affecting the gene represented in this entry.

DB03948; DB00993; DB01033; DB00688; DB01024; DB00157; DB00811; DB06408; DB06103

Q96D03; P20839-3; P12268; O75928-2; Q9Y4B4; P78317; Q7KZS0

EC 1.1.1.205

3D-structure; Alternative splicing; CBS domain; Cytoplasm; Direct protein sequencing; Disease variant; DNA-binding; GMP biosynthesis; Leber congenital amaurosis; Metal-binding; Methylation; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Potassium; Proteomics identification; Purine biosynthesis; Reference proteome; Repeat; Retinitis pigmentosa; RNA-binding

A,B

42447.5

395

0.06

33.17

5.61

-6.1

-6.76

SPSB2

Homo sapiens (Human)

NA

GRCC9;SSB2

SPSB family

NA

Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820, PubMed:21199876). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (PubMed:21199876). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (PubMed:21199876). {ECO:0000269|PubMed:15601820, ECO:0000269|PubMed:21199876}."

Intellectual developmental disorder, autosomal recessive 2 (MRT2) [MIM:607417]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT2 patients display mild intellectual disability with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. {ECO:0000269|PubMed:15557513, ECO:0000269|PubMed:28143899}. The disease is caused by variants affecting the gene represented in this entry.

NA

G5E9A7; Q15369; Q53EP0-3; O60333-2; Q16656-4; Q96IZ0; P16284; Q92569; O60260-5; Q99873; Q6P9E2; Q9Y3C5; Q96GM5; P61086; P08670; P09052

NA

3D-structure; Alternative splicing; Cytoplasm; Host-virus interaction; Proteomics identification; Reference proteome; Ubl conjugation pathway

A,B

22703.1

207

0.09

50.84

5.98

-2.79

-6.44

treA

Escherichia coli (strain K12)

NA

JW1186;osmA;b1197

Glycosyl hydrolase 37 family

NA

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

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

NA

NA

3.2.1.28

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

A

57508.9

507

0.11

48.32

5.48

-10.13

-6.86

PDE10A

Homo sapiens (Human)

cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Cyclic nucleotide phosphodiesterase family

Phosphoric diester hydrolase

Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.

Dyskinesia, limb and orofacial, infantile-onset (IOLOD) [MIM:616921]: An autosomal recessive, early-onset hyperkinetic movement disorder characterized by axial hypotonia, dyskinesia of the limbs and trunk, orofacial dyskinesia, drooling, and dysarthria. The severity of the hyperkinesis is variable. {ECO:0000269|PubMed:27058446}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Striatal degeneration, autosomal dominant 2 (ADSD2) [MIM:616922]: An autosomal dominant disorder characterized by striatal degeneration and dysfunction of basal ganglia, resulting in hyperkinesis. {ECO:0000269|PubMed:27058447}. The disease is caused by variants affecting the gene represented in this entry.

DB08384; DB08386; DB08383; DB08389; DB00201; DB00975; DB08387; DB01113; DB08391; DB08811; DB09283; DB08814

NA

EC 3.1.4.17

3D-structure; Allosteric enzyme; Alternative initiation; Alternative splicing; cAMP; cAMP-binding; cGMP; cGMP-binding; Cytoplasm; Disease variant; Hydrolase; Metal-binding; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Repeat

A,B

37469.9

324

0.1

48.52

6.28

-4.08

-6.67

DNPEP

Homo sapiens (Human)

DAP; ASPEP

Peptidase M18 family

Peptidase

Likely to play an important role in intracellular protein and peptide metabolism. Aminopeptidase with specificity towards an acidic amino acid at the N-terminus.

Cohen-Gibson syndrome (COGIS) [MIM:617561]: An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability. {ECO:0000269|PubMed:25787343, ECO:0000269|PubMed:27193220, ECO:0000269|PubMed:27868325, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:28475857}. The disease is caused by variants affecting the gene represented in this entry.

DB00142

Q9ULA0; Q8TBB1; Q00013; Q9UPN6

EC 3.4.11.21

3D-structure; Acetylation; Alternative initiation; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein; Protease; Proteomics identification; Reference proteome; Zinc

A

50574.6

457

0.07

55.73

7.73

2.3

-6.88

CBR1

Homo sapiens (Human)

ProstaglandinE(2) 9reductase; Prostaglandin 9ketoreductase; NADPHdependent carbonyl reductase 1; Carbonyl reductase [NADPH] 1; CBR1; 15hydroxyprostaglandin dehydrogenase [NADP(+)]

Short-chain dehydrogenases/reductases (SDR) family

Short-chain dehydrogenases reductase

NADPH-dependent reductase with broad substratespecificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.

Growth hormone deficiency, isolated, 4 (IGHD4) [MIM:618157]: An autosomal recessive deficiency of growth hormone leading to early and severe growth failure and short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. {ECO:0000269|PubMed:10084571, ECO:0000269|PubMed:11232012, ECO:0000269|PubMed:12534354, ECO:0000269|PubMed:8528260, ECO:0000269|PubMed:9467553}. The disease is caused by variants affecting the gene represented in this entry.

DB03556; DB04463; DB00414; DB06263; DB11672; DB14635; DB00694; DB12161; DB00997; DB01039; DB00502; DB03394; DB09212; DB01046; DB00776; DB04216; DB02709; DB01698; DB05197; DB04844

O75828

EC 1.1.1.184

3D-structure; Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Proteomics identification; Reference proteome

A

30156.3

275

0.06

43.19

8.55

2.98

-6.54

PDHB

Homo sapiens (Human)

NA

PHE1B

NA

Oxidoreductase

Pyruvate dehydrogenase (acetyl-transferring) activity.Pyruvate dehydrogenase activity.

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.

DB00157; DB00119

P10515; P08559; P08559-1

1.2.4.1

3D-structure; Acetylation; Alternative splicing; Carbohydrate metabolism; Direct protein sequencing; Disease variant; Glucose metabolism; Metal-binding; Mitochondrion; Oxidoreductase; Phosphoprotein; Potassium; Proteomics identification; Pyruvate; Reference proteome; Thiamine pyrophosphate; Transit peptide; Tricarboxylic acid cycle

B,D

36554.4

329

0.09

29.78

6.66

-0.99

-7.12

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

-6.61

choA

Streptomyces sp. (strain SA-COO)

NA

NA

GMC oxidoreductase family

Oxidoreductase

Cholesterol oxidase activity.Flavin adenine dinucleotide binding.Steroid delta-isomerase activity.

Bothnia retinal dystrophy (BRD) [MIM:607475]: A type of retinitis punctata albescens. Affected individuals show night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration. {ECO:0000269|PubMed:10102298}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rod-cone dystrophy Newfoundland (NFRCD) [MIM:607476]: A rod-cone dystrophy reminiscent of retinitis punctata albescens but with a substantially lower age at onset and more-rapid and distinctive progression. Rod-cone dystrophies results from initial loss of rod photoreceptors, later followed by cone photoreceptors loss. {ECO:0000269|PubMed:11868161}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Retinitis punctata albescens (RPA) [MIM:136880]: A form of fleck retina disease characterized by aggregation of white flecks posteriorly in the retina, causing night blindness and delayed dark adaptation. It differs from fundus albipunctatus in being progressive and evolving to generalized atrophy of the retina. {ECO:0000269|PubMed:10102299, ECO:0000269|PubMed:11453974, ECO:0000269|PubMed:9326942}. The disease is caused by variants affecting the gene represented in this entry.

DB03147; DB02332

NA

1.1.3.6; 5.3.3.1

3D-structure; Cholesterol metabolism; Direct protein sequencing; FAD; Flavoprotein; Isomerase; Lipid metabolism; Oxidoreductase; Secreted; Signal; Steroid metabolism; Sterol metabolism

A

54367.8

498

0.1

30.62

6.69

-0.71

-6.7

RRM2B

Homo sapiens (Human)

NA

P53R2

Ribonucleoside diphosphate reductase small chain family

Oxidoreductase

Metal ion binding.Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.

Mitochondrial DNA depletion syndrome 8A (MTDPS8A) [MIM:612075]: A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy. {ECO:0000269|PubMed:17486094, ECO:0000269|PubMed:18504129}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Mitochondrial DNA depletion syndrome 8B (MTDPS8B) [MIM:612075]: A disease due to mitochondrial dysfunction and characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy. {ECO:0000269|PubMed:19667227}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5 (PEOA5) [MIM:613077]: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. {ECO:0000269|PubMed:19664747}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Rod-cone dystrophy, sensorineural deafness, and Fanconi-type renal dysfunction (RCDFRD) [MIM:268315]: An autosomal recessive disease characterized by visual impairment due to rod-cone dystrophy, sensorineural hearing loss, and Fanconi-type renal dysfunction resulting in rickets-like skeletal changes. Death may occur in childhood or young adulthood due to renal failure. Disease onset is before age 5 years. {ECO:0000269|PubMed:32827185}. The disease is caused by variants affecting the gene represented in this entry.

DB00242

Q13315; Q00987; O43929; Q9H4P4; Q7LG56; Q00987

1.17.4.1

3D-structure; Alternative splicing; Cytoplasm; Deafness; Deoxyribonucleotide synthesis; Disease variant; DNA damage; DNA repair; Iron; Metal-binding; Neuropathy; Nucleus; Oxidoreductase; Primary mitochondrial disease; Progressive external ophthalmoplegia; Proteomics identification; Reference proteome

A,B

32464.8

287

0.15

44.18

5.48

-5.86

-6.17

MYH7

Homo sapiens (Human)

Myosin heavy chain, cardiac muscle beta isoform; Myosin heavy chain slow isoform; Myosin heavy chain 7; MyHCslow; MyHCbeta; MYH7

TRAFAC class myosin-kinesin ATPase superfamily, Myosin family

TRAFAC class myosin-kinesin ATPase

Muscle contraction.

Cardiomyopathy, familial hypertrophic, 1 (CMH1) [MIM:192600]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:10065021, ECO:0000269|PubMed:10329202, ECO:0000269|PubMed:10521296, ECO:0000269|PubMed:10563488, ECO:0000269|PubMed:10679957, ECO:0000269|PubMed:10862102, ECO:0000269|PubMed:11113006, ECO:0000269|PubMed:11133230, ECO:0000269|PubMed:11214007, ECO:0000269|PubMed:11424919, ECO:0000269|PubMed:11733062, ECO:0000269|PubMed:11861413, ECO:0000269|PubMed:11968089, ECO:0000269|PubMed:12081993, ECO:0000269|PubMed:12566107, ECO:0000269|PubMed:12590187, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:12820698, ECO:0000269|PubMed:12951062, ECO:0000269|PubMed:12974739, ECO:0000269|PubMed:12975413, ECO:0000269|PubMed:1417858, ECO:0000269|PubMed:15358028, ECO:0000269|PubMed:15483641, ECO:0000269|PubMed:1552912, ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:15856146, ECO:0000269|PubMed:15858117, ECO:0000269|PubMed:16199542, ECO:0000269|PubMed:16267253, ECO:0000269|PubMed:1638703, ECO:0000269|PubMed:16650083, ECO:0000269|PubMed:16938236, ECO:0000269|PubMed:17095604, ECO:0000269|PubMed:17372140, ECO:0000269|PubMed:18175163, ECO:0000269|PubMed:18403758, ECO:0000269|PubMed:1975517, ECO:0000269|PubMed:25182012, ECO:0000269|PubMed:7581410, ECO:0000269|PubMed:7731997, ECO:0000269|PubMed:7848441, ECO:0000269|PubMed:7874131, ECO:0000269|PubMed:7909436, ECO:0000269|PubMed:8250038, ECO:0000269|PubMed:8254035, ECO:0000269|PubMed:8268932, ECO:0000269|PubMed:8282798, ECO:0000269|PubMed:8343162, ECO:0000269|PubMed:8435239, ECO:0000269|PubMed:8483915, ECO:0000269|PubMed:8533830, ECO:0000269|PubMed:8655135, ECO:0000269|PubMed:8899546, ECO:0000269|PubMed:9544842, ECO:0000269|PubMed:9822100, ECO:0000269|PubMed:9829907}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 7A, myosin storage, autosomal dominant (CMYO7A) [MIM:608358]: A skeletal muscle disorder characterized by prominent axial and proximal weakening, spinal stiffness, severe scoliosis, with or without respiratory and cardiac involvement. The age at symptom onset can range from early childhood to late adulthood, and disease severity ranges from asymptomatic to severe muscular weakness and respiratory insufficiency. Histopathological examination shows variable findings including subsarcolemmal hyaline bodies in type 1 fibers. {ECO:0000269|PubMed:14520662, ECO:0000269|PubMed:15136674, ECO:0000269|PubMed:16684601, ECO:0000269|PubMed:17336526}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, dilated, 1S (CMD1S) [MIM:613426]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:11106718, ECO:0000269|PubMed:12379228, ECO:0000269|PubMed:15769782, ECO:0000269|PubMed:18506004, ECO:0000269|PubMed:21127202, ECO:0000269|PubMed:21846512}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myopathy, distal, 1 (MPD1) [MIM:160500]: A muscular disorder characterized by early-onset selective weakness of the great toe and ankle dorsiflexors, followed by weakness of the finger extensors. Mild proximal weakness occasionally develops years later after the onset of the disease. {ECO:0000269|PubMed:15322983, ECO:0000269|PubMed:17548557}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Congenital myopathy 7B, myosin storage, autosomal recessive (CMYO7B) [MIM:255160]: A skeletal muscle disorder characterized by the onset of scapuloperoneal muscle weakness in early childhood or young adulthood. Affected individuals have difficulty walking, steppage gait, and scapular winging due to shoulder girdle involvement. The severity and progression of the disorder is highly variable. Most patients develop respiratory insufficiency and restrictive lung disease. Some develop hypertrophic cardiomyopathy. Histopathological examination shows variable findings including subsarcolemmal hyaline bodies in type 1 fibers. {ECO:0000269|PubMed:25666907}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Left ventricular non-compaction 5 (LVNC5) [MIM:613426]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC5 is an autosomal dominant condition. {ECO:0000269|PubMed:18506004}. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

DB08378; DB14921

Q5SYC1; Q9BQD3; Q96DD0

NA

3D-structure; Actin-binding; ATP-binding; Calmodulin-binding; Cardiomyopathy; Coiled coil; Cytoplasm; Disease variant; Methylation; Motor protein; Muscle protein; Myosin; Nucleotide-binding; Phosphoprotein; Proteomics identification; Reference proteome; Thick filament

A

81702.7

716

0.11

36.28

6.43

-3.73

-6.95

SHMT1

Homo sapiens (Human)

NA

NA

SHMT family

Transferase

Glycine hydroxymethyltransferase activity.Identical protein binding.L-allo-threonine aldolase activity.MRNA 5'-UTR binding.Protein homodimerization activity.Pyridoxal phosphate binding.Serine binding.Translation repressor activity, nucleic acid binding.

Deafness, autosomal dominant, 77 (DFNA77) [MIM:618915]: A form of non-syndromic deafness characterized by adult onset of bilateral, postlingual, mild-to-severe sensorineural hearing loss. Sensorineural hearing loss 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:31273342}. The gene represented in this entry is involved in disease pathogenesis.

DB02800; DB00145; DB01055; DB02824; DB00114; DB00116; DB02067

P26196; Q9H8Y8; P50213; P45984; Q99750; P34896; P0DMM9

2.1.2.1

3D-structure; Acetylation; Alternative splicing; Cytoplasm; One-carbon metabolism; Proteomics identification; Pyridoxal phosphate; Reference proteome; Transferase

A

51456.1

470

0.08

37.11

6.78

-0.97

-6.46

CACNA1G

Homo sapiens (Human)

Voltage-gated calcium channel alpha subunit Cav3.1; Voltage-dependent T-type calcium channel; NBR13; Cav3.1c; CACNA1G

Calcium channel alpha-1 subunit (TC 1.A.1.11) family, CACNA1G subfamily

Voltage-gated ion channel

Voltage-sensitive calcium channels (vscc) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release and gene expression.

Spinocerebellar ataxia 42 (SCA42) [MIM:616795]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42 is a slowly progressive, autosomal dominant form with variable severity. {ECO:0000269|PubMed:26456284, ECO:0000269|PubMed:26715324}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits (SCA42ND) [MIM:618087]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA42ND is an early-onset, severe form associated with motor and cognitive impairment, cerebellar atrophy as well as variable features such as facial dysmorphisms, digital anomalies, microcephaly and epilepsy. SCA42ND inheritance is autosomal dominant. {ECO:0000269|PubMed:29878067}. The disease is caused by variants affecting the gene represented in this entry.

DB09227; DB09231; DB13746; DB11148; DB11093; DB11348; DB14481; DB09061; DB00568; DB09235; DB00228; DB00153; DB00593; DB04841; DB09238; DB14009; DB05246; DB01388; DB14011; DB00622; DB01115; DB06712; DB09089; DB00347; DB00661; DB00909

NA

NA

3D-structure; Alternative splicing; Calcium; Calcium channel; Calcium transport; Cell membrane; Cytoplasm; Disease variant; Glycoprotein; Ion channel; Ion transport; Membrane; Neurodegeneration; Phosphoprotein; Proteomics identification; Reference proteome; Repeat; Spinocerebellar ataxia; Transmembrane; Transmembrane helix; Transport; Voltage-gated channel

A

116116

1014

0.13

33.06

6.61

-2.04

-6.51