Malaria DXR

Plasmodium falciparum (isolate HB3)

IspC; DXR; DXP reductoisomerase; DOXP reductoisomerase; 2-C-Methyl-d-erythritol 4-phosphate synthase; 1-deoxyxylulose-5-phosphate reductoisomerase

DXR family

Short-chain dehydrogenases reductase

Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).

Ichthyosis, congenital, autosomal recessive 11 (ARCI11) [MIM:602400]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:17273967, ECO:0000269|PubMed:18843291}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 1.1.1.267

3D-structure; Apicoplast; Isoprene biosynthesis; Magnesium; Manganese; Metal-binding; NADP; Oxidoreductase; Plastid; Transit peptide

A

46644.4

410

0.09

36.77

6.95

-0.14

-7.5

IL21R

Homo sapiens (Human)

UNQ3121/PRO10273; Novel interleukin receptor; NILR; Interleukin-21 receptor; IL21 receptor; IL-21R; IL-21 receptor; CD360

Type I cytokine receptor family, Type 4 subfamily

Cytokine receptor

This is a receptor for interleukin-21.

Immunodeficiency 56 (IMD56) [MIM:615207]: An autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B-cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens. {ECO:0000269|PubMed:23440042}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chromosomal aberrations involving IL21R is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;16)(q27;p11), with BCL6.

NA

P29972

NA

3D-structure; Chromosomal rearrangement; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Membrane; Proteomics identification; Receptor; Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix

A,C,B

48376.5

446

0.1

43.94

8.24

3.56

-7.39

GRM3

Homo sapiens (Human)

mGLUR3; Group III metabotropic glutamate receptor; GPRC1C

G-protein coupled receptor 3 family

GPCR glutamate

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

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

DB05096

NA

NA

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

A

50355.5

445

0.11

38.26

6.52

-1.53

-7.64

PNP

Homo sapiens (Human)

PNP; Inosine phosphorylase

PNP/MTAP phosphorylase family

Pentosyltransferase

The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta- (deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.

Purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]: A disorder that interrupts both the catabolism of inosine into hypoxanthine and guanosine into guanine, and leads to the accumulation of guanosine, inosine, and their deoxified by-products. The main clinical presentation is recurrent infections due to severe T-cell immunodeficiency. Some patients also have neurologic impairment. {ECO:0000269|PubMed:1384322, ECO:0000269|PubMed:3029074, ECO:0000269|PubMed:8931706}. The disease is caused by variants affecting the gene represented in this entry.

DB03881; DB03551; DB02222; DB02391; DB03609; DB01667; DB04260; DB02796; DB04753; DB00640; DB00242; DB00900; DB06185; DB02377; DB02857; DB04754; DB04757; DB04076; DB02230; DB04335; DB02568; DB03101

P05067; Q9UQM7; O14576-2; P06241; P14136; Q92993-2; Q9BXM7; P00491; P17612; P63000; Q92673; Q15583

EC 2.4.2.1

3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Disease variant; Glycosyltransferase; Phosphoprotein; Proteomics identification; Purine salvage; Reference proteome; Transferase

A,B,C

31849.2

288

0.1

34.77

6.42

-1.63

-7.32

NAALAD2

Homo sapiens (Human)

NAALADase II; NAALAD2

Peptidase M28 family, M28B subfamily

Peptidase

Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivate the peptide neurotransmitter N- acetylaspartylglutamate.

Dystonia 1, torsion, autosomal dominant (DYT1) [MIM:128100]: A primary torsion dystonia, and the most common and severe form. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 1 is characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body, in the absence of other neurological symptoms. Typically, symptoms develop first in an arm or leg in middle to late childhood and progress in approximately 30% of patients to other body regions (generalized dystonia) within about five years. 'Torsion' refers to the twisting nature of body movements observed in DYT1, often affecting the trunk. Distribution and severity of symptoms vary widely between affected individuals, ranging from mild focal dystonia to severe generalized dystonia, even within families. {ECO:0000269|PubMed:14970196, ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:16361107, ECO:0000269|PubMed:17428918, ECO:0000269|PubMed:18167355, ECO:0000269|PubMed:18477710, ECO:0000269|PubMed:18827015, ECO:0000269|PubMed:19955557, ECO:0000269|PubMed:20169475, ECO:0000269|PubMed:21102408, ECO:0000269|PubMed:24930953, ECO:0000269|PubMed:27490483, ECO:0000269|PubMed:9288096}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Arthrogryposis multiplex congenita 5 (AMC5) [MIM:618947]: A form of arthrogryposis multiplex congenita, a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. AMC5 is an autosomal recessive form characterized by severe congenital contractures, developmental delay, strabismus and tremor. {ECO:0000269|PubMed:28516161, ECO:0000269|PubMed:29053766, ECO:0000269|PubMed:30244176}. The disease is caused by variants affecting the gene represented in this entry.

NA

Q9UHD4; Q6NTF9-3; B2RUZ4; O76024

EC 3.4.17.21

3D-structure; Alternative splicing; Calcium; Carboxypeptidase; Cell membrane; Dipeptidase; Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; Multifunctional enzyme; Protease; Proteomics identification; Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix; Zinc

A

77761.6

690

0.12

39.42

8.48

4.65

-6.74

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

-7.51

CA4

Homo sapiens (Human)

Carbonic anhydrase 4; Carbonate dehydratase IV; CAIV

Alpha-carbonic anhydrase family

Alpha-carbonic anhydrase

May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid. Reversible hydration of carbon dioxide.

Retinitis pigmentosa 17 (RP17) [MIM:600852]: 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:15563508, ECO:0000269|PubMed:17652713, ECO:0000269|PubMed:20450258}. The disease is caused by variants affecting the gene represented in this entry. Defective acid overload removal from retina and retinal epithelium, due to mutant CA4, is responsible for photoreceptor degeneration, indicating that impaired pH homeostasis is the most likely cause underlying the RP17 phenotype.

DB00819; DB00436; DB00562; DB01194; DB00606; DB01144; DB00869; DB08846; DB00311; DB00774; DB00703; DB00232; DB09460; DB00273; DB01021; DB00909

NA

EC 4.2.1.1

3D-structure; Alternative splicing; Cell membrane; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein; Lyase; Membrane; Metal-binding; Proteomics identification; Reference proteome; Retinitis pigmentosa; Signal; Zinc

A,B

27055.7

235

0.09

44.3

6.87

-0.36

-6.78

CHAT

Homo sapiens (Human)

NA

NA

Carnitine/choline acetyltransferase family

Transferase

Choline O-acetyltransferase activity.

Myasthenic syndrome, congenital, 6, presynaptic (CMS6) [MIM:254210]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS6 affected individuals have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement. CMS6 inheritance is autosomal recessive. {ECO:0000269|PubMed:11172068, ECO:0000269|PubMed:12756141}. The disease is caused by variants affecting the gene represented in this entry.

DB00122; DB14006; DB00184

Q6H8Q1-8; Q8N302-2; Q9NXL2-1; Q6XD76; Q9UII2; Q8TBE0; Q9UQB8-6; Q9ULD4-2; Q9NSI6-4; Q6P5X5; Q96LL4; P20807-4; O00257-3; Q6ZP82-1; O95674; Q9H3R5; Q8WUX9; Q9H2A9; Q3SX64; Q92782-2; Q14117; O14641; Q658K8; Q6UXG2-3; O00472; Q6NXG1; Q15910-2; Q8IZU1; P15407; P55318; Q06547-3; P23769-2; P23771; Q15486; Q8IV36; Q4VB01; Q53GQ0; P10809; P41134; Q9NZH6; Q8NA54; Q86U28; P17275; Q8N5Z5; Q6P597; P08727; Q14525; Q8IUC2; Q6IAA8; Q14847-2; P27338; Q9GZQ8; Q53S70; Q5JXC2; A0A0A0MR05; Q8NEH6; Q8TCY5; Q6IN84-2; Q96H12; P01106; P41271-2; P14598; Q9GZM8; Q5BJF6-2; Q9H8K7; Q9NR21-5; Q5VU43-8; Q13956; Q5SXH7-1; Q96T60; Q96I34; Q86UA1; Q15311; Q8TBY0; Q04206; P47804-3; Q9H0X6; P62899; Q66K80; Q9BY12-3; Q86SQ7-2; Q7Z6I5; Q496A3; Q7Z698; Q9C004; Q92783-2; Q8N4C7; O75528; Q15814; O15273; Q96A09; Q8WTV1; Q53NU3; Q71RG4-4; Q86WT6-2; Q9Y3Q8; Q99598; P49459; P11441; Q9H270; P19544-6; Q53FD0-2; Q3KNS6-3

2.3.1.6

3D-structure; Acyltransferase; Alternative splicing; Congenital myasthenic syndrome; Direct protein sequencing; Disease variant; Neurotransmitter biosynthesis; Phosphoprotein; Proteomics identification; Reference proteome; Transferase

A

66365.9

595

0.08

53.36

8.16

4.64

-7.3

ECE1

Homo sapiens (Human)

ECE-1

Peptidase M13 family

Peptidase

Converts big endothelin-1 to endothelin-1.

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

DB07171

P49760; A8MQ03; Q8IUG1; P60370; P60410

EC 3.4.24.71

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

A

75247.9

660

0.12

46.29

5.33

-18.3

-6.65

SLC19A1

Homo sapiens (Human)

Reduced folate carrier protein; RFC1; RFC; Placental folate transporter; Intestinal folate carrier 1; IFC-1; Folate transporter 1; FOLT; FLOT1

Reduced folate carrier (RFC) transporter (TC 2.A.48) family

NA

Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely the folate receptor, the folate transporter, and a V-type H(+)-pump.

Megaloblastic anemia, folate-responsive (MEGAF) [MIM:601775]: An autosomal recessive metabolic disorder characterized by megaloblastic anemia resulting from decreased folate transport into erythrocytes. Disease manifestations include hemolytic anemia, hyperhomocysteinemia, and low vitamin B12. Serum folate levels are normal, but erythrocyte folate levels are decreased. Treatment with oral folate corrects the anemia and normalizes homocysteine. {ECO:0000269|PubMed:32276275}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 114, folate-responsive (IMD114) [MIM:620603]: An autosomal recessive immunologic disorder manifesting in early infancy and characterized by recurrent skin and respiratory infections, mucosal bleeding, oral ulcers, chronic diarrhea, and poor overall growth. Affected individuals have lymphopenia, low serum immunoglobulins, and impaired T cell proliferation. Some patients have global developmental delay. {ECO:0000269|PubMed:36517554, ECO:0000269|PubMed:36745868}. The disease is caused by variants affecting the gene represented in this entry.

DB11256; DB00563; DB00642; DB06813; DB01157

Q7Z3Y9

NA

3D-structure; Acetylation; Alternative splicing; Antiport; Cell membrane; Disease variant; Folate-binding; Glycoprotein; Hereditary hemolytic anemia; Membrane; Phosphoprotein; Proteomics identification; Reference proteome; Transmembrane; Transmembrane helix; Transport

A

46087.7

407

0.15

34.62

9.82

17.33

-7.47

KDM4E

Homo sapiens (Human)

Lysine-specific demethylase 4D-like; KDM4DL; KDM4D-like protein

JHDM3 histone demethylase family

Paired donor oxygen oxidoreductase

Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code.

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}.

NA

NA

EC 1.14.11.-

3D-structure; Chromatin regulator; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase; Reference proteome; Transcription; Transcription regulation; Zinc

A

35131.5

305

0.14

39.34

6

-6.1

-7.07

DBH

Homo sapiens (Human)

NA

NA

Copper type II ascorbate-dependent monooxygenase family

Oxidoreductase

Catalytic activity.Copper ion binding.Dopamine beta-monooxygenase activity.L-ascorbic acid binding.

Orthostatic hypotension 1 (ORTHYP1) [MIM:223360]: A form of orthostatic hypotension due to congenital dopamine beta-hydroxylase deficiency. Orthostatic hypotension, also known as postural hypotension, is a finding defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure occurring 3 minutes after a person has risen from supine to standing. Symptoms include dizziness, blurred vision, and sometimes syncope. ORTHYP1 is an autosomal recessive condition apparent from infancy or early childhood and characterized by low plasma and urinary levels of norepinephrine and epinephrine, and episodic hypoglycemia. {ECO:0000269|PubMed:11857564}. The disease is caused by variants affecting the gene represented in this entry.

DB00126; DB06774; DB09130; DB05394; DB00822; DB00988; DB00968; DB00550

P00352; P63010-2; Q04656; Q8WUW1; Q9UNS2; Q71DI3; P61978; Q9Y2M5; Q92876; P08727; Q14693; P0DPK4; Q6GQQ9-2; P27986-2; Q9ULX5; Q96D59; Q8N6K7-2; Q9GZS3; Q8IUW3; Q86WT6-2

1.14.17.1

3D-structure; Catecholamine biosynthesis; Copper; Cytoplasmic vesicle; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; Proteomics identification; Reference proteome; Secreted; Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C

A,B

123694

1094

0.1

51.85

5.84

-24.5

-7.37

CALCR-RAMP1/RAMP2/RAMP3

Homo sapiens (Human)

Complex of Calcitonin receptor and Receptor activity-modifying protein

RAMP family

NA

Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.

Immunodeficiency 9 (IMD9) [MIM:612782]: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed. {ECO:0000269|PubMed:16147976, ECO:0000269|PubMed:16582901}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myopathy, tubular aggregate, 2 (TAM2) [MIM:615883]: A rare congenital myopathy characterized by regular arrays of membrane tubules on muscle biopsies without additional histopathological hallmarks. Tubular aggregates in muscle are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. TAM2 patients have myopathy and pupillary abnormalities. {ECO:0000269|PubMed:24591628, ECO:0000269|PubMed:28058752}. The disease is caused by variants affecting the gene represented in this entry.

DB01278

Q16602; P21145; Q5J8X5; Q16617

NA

3D-structure; Cell membrane; Disulfide bond; Membrane; Proteomics identification; Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport

A

63832.6

569

0.12

22.42

5.07

-16.96

-7.12

CH colG

Hathewaya histolytica (Clostridium histolyticum)

Microbial collagenase; Gelatinase ColG; Collagenase ColG; Class I collagenase

Peptidase M9B family, Collagenase subfamily

NA

Clostridial collagenases are among the most efficient degraders of eukaryotic collagen known; saprophytes use collagen as a carbon source while pathogens additionally digest collagen to aid in host colonization. Has both tripeptidylcarboxypeptidase on Gly-X-Y and endopeptidase activities; the endopeptidase cuts within the triple helix region of collagen while tripeptidylcarboxypeptidase successively digests the exposed ends, thus clostridial collagenases can digest large sections of collagen. Active on soluble type I collagen, insoluble collagen, azocoll, soluble PZ-peptide (all collagenase substrates) and gelatin. The full-length protein has collagenase activity, while the in vivo derived C-terminally truncated shorter versions only act on gelatin. In vitro digestion of soluble calf skin collagen fibrils requires both ColG and ColH; ColG forms missing the second collagen-binding domain are also synergistic with ColH, although their overall efficiency is decreased. The activator domain (residues 119-388) and catalytic subdomain (389-670) open and close around substrate using a Gly-rich hinge (387-397), allowing digestion when the protein is closed. Binding of collagen requires Ca(2+) and is inhibited by EGTA; the collagen-binding domain (CBD, S3a plus S3b) specifically recognizes the triple-helical conformation made by 3 collagen protein chains in the triple-helical region. Isolated CBD (S3a plus S3b) binds collagen fibrils and sheets of many tissues.

Intellectual developmental disorder, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest intellectual disability associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism. {ECO:0000269|PubMed:15586325, ECO:0000269|PubMed:16538222, ECO:0000269|PubMed:16541399, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17468742, ECO:0000269|PubMed:23356856, ECO:0000269|PubMed:25666439}. The disease is caused by variants affecting the gene represented in this entry.

NA

NA

EC 3.4.24.3

3D-structure; Calcium; Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease; Pharmaceutical; Protease; Repeat; Secreted; Signal; Virulence; Zinc; Zymogen

A

44751.2

386

0.15

27.33

5.77

-7.33

-6.88

CA9

Homo sapiens (Human)

Renal cell carcinoma-associated antigen G250; RCC-associated antigen G250; PMW1; P54/58N; Membrane antigen MN; MN; G250 antigen (MN/CA IX/G250); G250; Carbonic anhydrase 9; Carbonate dehydratase IX; C

Alpha-carbonic anhydrase family

Alpha-carbonic anhydrase

Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Reversible hydration of carbon dioxide.

Hydroxykynureninuria (HYXKY) [MIM:236800]: An inborn error of amino acid metabolism characterized by massive urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid. Affected individuals manifest renal tubular dysfunction, metabolic acidosis, psychomotor retardation, non-progressive encephalopathy, and muscular hypertonia. {ECO:0000269|PubMed:17334708, ECO:0000269|PubMed:28792876}. The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Vertebral, cardiac, renal, and limb defects syndrome 2 (VCRL2) [MIM:617661]: An autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects. {ECO:0000269|PubMed:28792876}. The disease is caused by variants affecting the gene represented in this entry.

DB00562; DB00606; DB12741; DB08846; DB05304; DB00774; DB09460; DB00909

P21291; O76003

EC 4.2.1.1

3D-structure; Cell membrane; Cell projection; Direct protein sequencing; Disulfide bond; Glycoprotein; Lyase; Membrane; Metal-binding; Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc

A,B,C,D

27522.8

251

0.08

48.97

5.48

-7.5

-7.05

MPO

Homo sapiens (Human)

MPO

Peroxidase family, XPO subfamily

Peroxidases

Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acidin physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.

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.

DB06111; DB00233; DB00006; DB02300; DB06774; DB00958; DB06468; DB00833; DB00535; DB00515; DB00847; DB00250; DB05161; DB01225; DB00583; DB01065; DB00461; DB04821; DB00104; DB00526; DB00550; DB00208; DB06823; DB00500; DB04827

P27918; Q9UNE7

EC 1.11.2.2

3D-structure; Alternative splicing; Calcium; Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; Heme; Hydrogen peroxide; Iron; Lysosome; Metal-binding; Oxidation; Oxidoreductase; Peroxidase; Proteomics identification; Reference proteome; Signal

A,B,E,F,I,J,M,N

53052.6

466

0.08

40.64

9.48

15.12

-6.55

PPP1CA

Homo sapiens (Human)

Serine/threonine-protein phosphatase PP1-alpha catalytic subunit; Protein phosphatase 1alpha; PPP1A; PP-1A

PPP phosphatase family, PP-1 subfamily

Phosphoric monoester hydrolase

Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective. Dephosphorylates CENPA. Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy. Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets.

A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies. {ECO:0000269|PubMed:15007172}.; DISEASE: Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B. {ECO:0000269|PubMed:15007172}.

DB02506

Q6ZMQ8; P31749; O14727; P05067; O15169; P38398; O95400; Q99459; P12830; Q8TEP8; Q9NX63; Q6PJW8; Q96S65; Q9H175; Q92796; P05198; P55199; Q9BZS1; P42858; Q8NI77; Q8NG31; Q5S007; O00566; Q9UPR0; Q96QC0; Q96KQ4; Q8WUF5; O75807; Q5SWA1; Q96T49; Q6NYC8; P41236; Q5T8A7; Q86WC6; Q6NXS1; O14990; O75864; Q86XI6; Q9UQK1; O95685; Q15435; Q12972; Q12972-1; Q12972-2; Q96SB3; P60484; P06400; Q5UIP0; Q14684; P04271; Q7Z5V6; A8K8P3; Q562F6; Q9H788; Q8TEC5; P63208; Q7Z699; P43405-2; Q9HCH5; Q14C87; Q5JTV8; Q05BL1; Q13625; Q4KMQ1; Q4KMQ1-2; Q8TEL6; P49815; P55072; Q9Y2W2; Q9H4A3; P16989; P49750; Q9HBF4; Q7Z3T8; O95405; O08785; P36313; K9N4V7; Q76TK5; O35867; O35274

EC 3.1.3.16

3D-structure; Acetylation; Alternative splicing; Carbohydrate metabolism; Cell cycle; Cell division; Cytoplasm; Direct protein sequencing; Glycogen metabolism; Host-virus interaction; Hydrolase; Manganese; Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase; Proteomics identification; Reference proteome

A

33626.3

294

0.11

44.81

5.16

-10.09

-6.48

CAD

Homo sapiens (Human)

CAD

CarA family; CarB family; Metallo-dependent hydrolases superfamily, DHOase family, CAD subfamily; Aspartate/ornithine carbamoyltransferase superfamily, ATCase family

Carbon-nitrogen ligase

This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).

Developmental and epileptic encephalopathy 50 (DEE50) [MIM:616457]: 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. DEE50 is an autosomal recessive, progressive disease with onset in infancy and favorable response to treatment with oral uridine. {ECO:0000269|PubMed:25678555, ECO:0000269|PubMed:28087732}. The disease is caused by variants affecting the gene represented in this entry.

DB00128; DB00130; DB03459

P27708; Q8N137; P63104

NA

3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Congenital disorder of glycosylation; Cytoplasm; Direct protein sequencing; Disease variant; Epilepsy; Hydrolase; Ligase; Magnesium; Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; Pyrimidine biosynthesis; Reference proteome; Repeat; Transferase; Zinc

A

38268.4

351

0.06

41.29

5.86

-10.56

-7.48

PKLR

Homo sapiens (Human)

NA

PKL;PK1

Pyruvate kinase family

Transferase

ATP binding.Kinase activity.Magnesium ion binding.Potassium ion binding.Pyruvate kinase activity.

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.

DB02726; DB00787; DB04551; DB16236; DB00119

Q9UBL6-2

2.7.1.40

3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; Disease variant; Glycolysis; Hereditary hemolytic anemia; Kinase; Magnesium; Manganese; Metal-binding; Nucleotide-binding; Phosphoprotein; Potassium; Proteomics identification; Pyruvate; Reference proteome; Transferase

A,B,C,D

45695.1

421

0.06

34.44

6.88

-0.35

-7.47

LONP1

Homo sapiens (Human)

Serine protease 15; Mitochondrial ATP-dependent protease Lon; Lon protease-like protein; LONP1; LONP; LONHs

Peptidase S16 family

Peptidase

ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single- stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site- specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein.

CODAS syndrome (CODASS) [MIM:600373]: A rare syndrome characterized by the combination of cerebral, ocular, dental, auricular, and skeletal features. These include developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts. {ECO:0000269|PubMed:25574826, ECO:0000269|PubMed:25808063}. The disease is caused by variants affecting the gene represented in this entry.

NA

P02666; P36776-1

EC 3.4.21.53

3D-structure; Alternative splicing; ATP-binding; Cataract; Deafness; Disease variant; DNA-binding; Dwarfism; Hydrolase; Mitochondrion; Nucleotide-binding; Protease; Proteomics identification; Reference proteome; Serine protease; Transit peptide

A,B

118797

1070

0.07

35.44

5.72

-18.18

-6.97