GGH
protein-codinggamma-glutamyl hydrolase, the group of Glutamine amidotransferase class 1 domain containing
Gene summary
This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GGH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003878.3. 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 | 2 | 1 | 3 | |||
| missense | 34 | 3 | 1 | 38 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 38 | 3 | 2 | 43 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003869.1 | 9 | MANE Select | |
| Ensembl | ENSP00000260118.6 | 9 | MANE Select | |
| RefSeq | NP_001397855.1 | 8 | Standard | |
| Ensembl | ENSP00000504520.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fluoropyrimidine Pathway, Pharmacodynamics
- Folate biosynthesis - Homo sapiens (human)
- Methotrexate Pathway (Cancer Cell), Pharmacodynamics
- Folate malabsorption, hereditary
- Methylenetetrahydrofolate Reductase Deficiency (MTHFRD)
Biological Process
- proteolysis
- response to zinc ion
- response to insulin
- neutrophil degranulation
- response to ethanol
Molecular Function
- exopeptidase activity
- omega peptidase activity
- gamma-glutamyl-peptidase activity
Cellular Component
- extracellular region
- extracellular space
- nucleus
- vacuole
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260118
- Coding exons
- 9
- Length
- 24093
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125734
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.451 | 144 | 160 | 0.900 | 0.00000778 | 2067 |
| Missense (PolyPhen) | 40 | 54.555 | 0.73321 | 727 | ||
| Synonymous | -0.289 | 62 | 59.2 | 1.05 | 0.00000300 | 568 |
| Loss of Function | 2.96 | 3 | 15.7 | 0.192 | 6.57e-7 | 222 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0.00021 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha- glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.;
Recessive Scores
- pRec
- 0.237
Intolerance Scores
- LoFtool
- 0.592
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.928
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |