GGH (Gamma-Glutamyl Hydrolase)
Gene encoding an enzyme involved in folate metabolism and antifolate drug resistance
Gene Information Card
| Symbol | GGH |
|---|---|
| Full Name | Gamma-Glutamyl Hydrolase |
| Gene Type | protein-coding |
| Chromosomal Location | 8q12.3 |
| NCBI Gene ID | 8836 ncbi.nlm.nih.gov/gene/8836 |
| Ensembl ID | ENSG00000104419 |
| UniProt ID | Q92820 |
| OMIM ID | 601509 |
| HGNC ID | 4248 |
| Aliases | GH, GGH1, gamma-Glu-X carboxypeptidase |
Description
The GGH gene encodes gamma-glutamyl hydrolase, an enzyme that catalyzes the hydrolysis of polyglutamate chains from folates and antifolates, thereby regulating intracellular folate homeostasis and modulating the activity of methotrexate and other antifolate drugs. It is expressed in various tissues and is implicated in cancer drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered GGH expression affects intracellular polyglutamylation of antifolates, leading to drug resistance | ClinVar, COSMIC |
| Methotrexate resistance | Increased GGH activity reduces methotrexate polyglutamate accumulation, decreasing drug efficacy | NCBI, PubMed |
| Folate deficiency | Dysregulation of GGH can disrupt folate metabolism, potentially contributing to neural tube defects | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Small intestine | 8.9 | Medium |
| Breast | 6.3 | Low |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.0 | Hepatocellular carcinoma cell line |
| MCF7 | 7.2 | Breast cancer cell line |
| A549 | 5.8 | Lung cancer cell line |
| K562 | 4.5 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.452C>T (p.Thr151Met) | Missense | 0.01% | Reduced enzyme activity |
| c.1A>G (p.Met1Val) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.1105G>A (p.Gly369Ser) | Missense | 0.02% | Altered substrate specificity |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Thr151Met reduce catalytic activity, impairing folate polyglutamate hydrolysis.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
No evidence of dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • gamma-glutamyl hydrolase activity (GO:0004175) | • folate metabolic process (GO:0006766) |
| • cytoplasm (GO:0005737) | • lysosome (GO:0005764) |
Pathways
• Folate metabolism (Reactome: R-HSA-196757)
• Methotrexate action and resistance (KEGG: hsa01523)
Protein Summary
Gamma-glutamyl hydrolase is a lysosomal enzyme that removes polyglutamate chains from folates and antifolates, regulating intracellular folate pools and influencing the efficacy of antifolate chemotherapeutics like methotrexate. The protein is a homodimer with a molecular weight of approximately 36 kDa per subunit.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GGH Knockout HEK293 Cell Line | EDJ-KQ6381 | Human | 8836 | Details Get a Quote |
| PGGHG Knockout HEK293 Cell Line | EDJ-KQ9467 | Human | 80162 | Details Get a Quote |
| PGGHG Knockout A-549 Cell Line | EDJ-KQ36173 | Human | 80162 | Details Get a Quote |
| PGGHG Knockout HCT 116 Cell Line | EDJ-KQ36174 | Human | 80162 | Details Get a Quote |
| PGGHG Knockout HeLa Cell Line | EDJ-KQ36175 | Human | 80162 | Details Get a Quote |
| GGH Knockout A-549 Cell Line | EDJ-KQ30383 | Human | 8836 | Details Get a Quote |
| GGH Knockout HCT 116 Cell Line | EDJ-KQ30384 | Human | 8836 | Details Get a Quote |
| GGH Knockout HeLa Cell Line | EDJ-KQ30385 | Human | 8836 | Details Get a Quote |
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