GSTA1: Glutathione S-Transferase Alpha 1
Key enzyme in xenobiotic metabolism and oxidative stress response
Gene Information Card
| Symbol | GSTA1 |
|---|---|
| Full Name | Glutathione S-Transferase Alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.2 |
| NCBI Gene ID | 2938 ncbi.nlm.nih.gov/gene/2938 |
| Ensembl ID | ENSG00000143921 |
| UniProt ID | P08263 |
| OMIM ID | 138359 |
| HGNC ID | 4626 |
| Aliases | GST2, GSTA1-1, GTH1, HA subunit 1, GST class-alpha |
Description
GSTA1 encodes a member of the alpha class of glutathione S-transferases (GSTs), which are phase II detoxification enzymes. The protein catalyzes the conjugation of reduced glutathione to a wide variety of electrophilic compounds, including carcinogens, therapeutic drugs, and products of oxidative stress. GSTA1 is highly expressed in liver and kidney and plays a critical role in cellular defense against xenobiotics and reactive oxygen species. Genetic polymorphisms in GSTA1 are associated with altered enzyme activity and may influence susceptibility to cancer and response to chemotherapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Reduced GSTA1 expression leads to impaired detoxification of carcinogens, increasing DNA damage and tumorigenesis risk. | PMID: 25642768 |
| Colorectal cancer | Polymorphic variants (e.g., GSTA1*B) result in lower enzyme activity, associated with increased risk of colorectal adenoma and cancer. | PMID: 17661439 |
| Breast cancer | GSTA1 promoter polymorphisms modulate enzyme expression, influencing susceptibility and prognosis. | PMID: 20672375 |
| Acute myeloid leukemia (AML) | Low GSTA1 activity may reduce detoxification of chemotherapeutic agents, affecting treatment outcome. | PMID: 23349010 |
| Oxidative stress-related disorders | GSTA1 deficiency impairs glutathione conjugation of lipid peroxidation products, contributing to cellular damage. | PMID: 12432960 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 124.3 | High |
| Kidney | 45.6 | Medium |
| Small intestine | 32.1 | Medium |
| Adrenal gland | 18.7 | Low |
| Lung | 12.4 | Low |
| Heart | 5.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 156.8 | High expression; used as model for hepatic detoxification |
| HEK293 (embryonic kidney) | 42.3 | Moderate expression |
| A549 (lung) | 8.9 | Low expression |
| MCF7 (breast) | 3.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.−69C>T (rs3957357) | SNP (promoter) | 30-40% in Caucasians | Reduces transcriptional activity; associated with lower GSTA1 expression |
| c.−52G>A (rs3957356) | SNP (promoter) | 25-35% in Asians | Alters transcription factor binding; decreased enzyme activity |
| p.Glu208Lys (rs1051775) | Missense | <1% | Unknown functional impact; rare variant |
| c.429+1G>A | Splice donor | <0.1% | Predicted to disrupt splicing; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Promoter SNPs (c.−69C>T, c.−52G>A) reduce gene expression and enzyme activity, impairing detoxification capacity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GSTA1.
Dominant Negative (DN)
No dominant-negative variants described for GSTA1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glutathione conjugation (Reactome: R-HSA-156590)
• Phase II - conjugation of compounds (Reactome: R-HSA-156580)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
• Drug metabolism - glutathione S-transferases (KEGG: hsa00480)
• Chemical carcinogenesis - DNA adducts (KEGG: hsa05204)
Protein Summary
GSTA1 is a 25.6 kDa cytosolic protein composed of 222 amino acids. It functions as a homodimer (GSTA1-1) and catalyzes the nucleophilic attack of reduced glutathione on electrophilic substrates. The active site contains a conserved tyrosine residue (Tyr9) essential for catalytic activity. GSTA1 exhibits broad substrate specificity, including 1-chloro-2,4-dinitrobenzene (CDNB), ethacrynic acid, and various lipid peroxidation products. The protein is highly expressed in liver and kidney, where it constitutes up to 2% of total soluble protein. Post-translational modifications include S-glutathionylation, which modulates activity under oxidative stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSTA1 Knockout HEK293 Cell Line | EDJ-KQ2570 | Human | 2938 | Details Get a Quote |
| GSTA1 Knockout HeLa Cell Line | EDJ-KQ53448 | Human | 2938 | Details Get a Quote |
| GSTA1 Knockout A-549 Cell Line | EDJ-KQ61922 | Human | 2938 | Details Get a Quote |
| GSTA1 Knockout HCT 116 Cell Line | EDJ-KQ70401 | Human | 2938 | Details Get a Quote |
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