GSTA4: Glutathione S-Transferase Alpha 4
A key enzyme in cellular detoxification and oxidative stress response
Gene Information Card
| Symbol | GSTA4 |
|---|---|
| Full Name | Glutathione S-Transferase Alpha 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p12.2 |
| NCBI Gene ID | 2941 ncbi.nlm.nih.gov/gene/2941 |
| Ensembl ID | ENSG00000170899 |
| UniProt ID | O15217 |
| OMIM ID | 605450 |
| HGNC ID | 4632 |
| Aliases | GST A4-4, GTA4, GSTA4-4 |
Description
GSTA4 encodes a member of the alpha class of glutathione S-transferases (GSTs), which catalyze the conjugation of reduced glutathione to a variety of electrophilic substrates, including the lipid peroxidation product 4-hydroxynonenal (4-HNE). This enzyme plays a critical role in cellular detoxification and protection against oxidative stress. GSTA4 is highly expressed in liver, kidney, and testis, and its activity is implicated in cancer susceptibility, neurodegenerative diseases, and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Reduced GSTA4 expression leads to accumulation of 4-HNE, promoting oxidative damage and tumor progression. | PMID: 23454731 |
| Alzheimer disease | GSTA4 detoxifies 4-HNE; decreased activity correlates with increased amyloid-beta toxicity and tau pathology. | PMID: 15590663 |
| Type 2 diabetes | GSTA4 polymorphisms associated with altered oxidative stress markers and insulin resistance. | PMID: 19096309 |
| Prostate cancer | Loss of GSTA4 expression linked to increased 4-HNE adducts and aggressive tumor phenotype. | PMID: 21804530 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 45.2 | High |
| Kidney | 28.7 | High |
| Testis | 22.1 | High |
| Heart | 8.4 | Medium |
| Brain | 5.1 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 52.3 | Hepatocellular carcinoma cell line |
| HEK293 | 18.6 | Embryonic kidney cells |
| MCF7 | 6.2 | Breast cancer cell line |
| A549 | 4.5 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.335A>G (p.His112Arg) | Missense | 0.01% (gnomAD) | Reduced catalytic activity toward 4-HNE |
| c.416C>T (p.Thr139Met) | Missense | 0.005% (gnomAD) | Altered substrate specificity |
| c.1A>G (p.Met1Val) | Start loss | <0.001% | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.His112Arg reduce enzymatic activity, impairing detoxification of 4-HNE and increasing oxidative stress.
Gain of Function (GOF)
No gain-of-function mutations reported in GSTA4.
Dominant Negative (DN)
No dominant-negative mutations described for GSTA4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glutathione metabolism (KEGG: hsa00480)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
• Drug metabolism - cytochrome P450 (KEGG: hsa00982)
• Chemical carcinogenesis (KEGG: hsa05204)
Protein Summary
GSTA4 is a 222-amino acid cytosolic protein that forms homodimers. It exhibits high catalytic efficiency for 4-hydroxynonenal (4-HNE), a toxic aldehyde generated during lipid peroxidation. The enzyme conjugates glutathione to 4-HNE, facilitating its elimination. GSTA4 also contributes to the metabolism of various xenobiotics and drugs. Its expression is regulated by NRF2 and other transcription factors in response to oxidative stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSTA4 Knockout HEK293 Cell Line | EDJ-KQ4812 | Human | 2941 | Details Get a Quote |
| GSTA4 Knockout A-549 Cell Line | EDJ-KQ27582 | Human | 2941 | Details Get a Quote |
| GSTA4 Knockout HeLa Cell Line | EDJ-KQ27583 | Human | 2941 | Details Get a Quote |
| GSTA4 Knockout HCT 116 Cell Line | EDJ-KQ70404 | Human | 2941 | Details Get a Quote |
