GGT1
protein-codinggamma-glutamyltransferase 1, the group of CD molecules|Gamma-glutamyltransferases
Gene summary
The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]
- GGT
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~34.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009285
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0009285
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009285
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009285
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Biochemical; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GGT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001288833.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 19 | 5 | 24 | |||
| missense | 67 | 13 | 1 | 81 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 69 | 32 | 6 | 107 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001275762.1 | 12 | MANE Select | |
| Ensembl | ENSP00000383232.1 | 12 | MANE Select | |
| RefSeq | NP_038265.2 | 12 | Standard | |
| RefSeq | NP_038347.2 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione metabolism - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- Taurine and hypotaurine metabolism - Homo sapiens (human)
- Busulfan Pathway, Pharmacodynamics
- Leukotriene modifiers pathway, Pharmacodynamics
Biological Process
- regulation of immune system process
- translation
- proteolysis
- cellular amino acid metabolic process
- glutamate metabolic process
Molecular Function
- peptidyltransferase activity
- leukotriene-C(4) hydrolase
- protein binding
- glutathione hydrolase activity
- hypoglycin A gamma-glutamyl transpeptidase activity
Cellular Component
- extracellular space
- plasma membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400382
- Coding exons
- 12
- Length
- 45255
- Individuals with no LoFs
- 125515
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 74
- Defined
- 125591
- p
- 0.000303
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.857 | 310 | 355 | 0.872 | 0.0000234 | 3609 |
| Missense (PolyPhen) | 71 | 101.12 | 0.70211 | 1054 | ||
| Synonymous | 0.0906 | 162 | 163 | 0.991 | 0.0000122 | 1187 |
| Loss of Function | 2.55 | 11 | 24.7 | 0.446 | 0.00000134 | 262 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000071 | 0.000062 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.0013 | 0.0012 | notable |
| European (Non-Finnish) | 0.00027 | 0.00026 | rare |
| South Asian | 0.00026 | 0.00023 | rare |
| Other | 0.00050 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates, and other gamma-glutamyl compounds. The metabolism of glutathione releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Isoform 3 seems to be inactive. {ECO:0000269|PubMed:20622017, ECO:0000269|PubMed:24047895, ECO:0000269|PubMed:7673200, ECO:0000269|PubMed:7759490, ECO:0000269|PubMed:8095045, ECO:0000269|PubMed:8827453}.;
- Disease
- DISEASE: Glutathionuria (GLUTH) [MIM:231950]: A very rare, autosomal recessive metabolic disorder characterized by the presence of glutathione in the urine, due to generalized gamma- glutamyl transpeptidase deficiency. Most patients manifest mild to moderate mental retardation, and behavioral disturbance. Seizures, tremor, marfanoid features and strabismus are observed in some patients. {ECO:0000269|PubMed:29483667}. Note=The disease is caused by mutations affecting the gene represented in this entry. A large homozygous deletion that removes several exons of all isoforms of GGT1 has been found in one family affected by glutathionuria. {ECO:0000269|PubMed:29483667}.;
Recessive Scores
- pRec
- 0.828
Intolerance Scores
- LoFtool
- 0.855
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.92
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.124
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |