GPX2: Glutathione Peroxidase 2 – Antioxidant Enzyme in Gastrointestinal Health and Cancer
A selenium-dependent glutathione peroxidase primarily expressed in the gastrointestinal tract, protecting against oxidative stress and implicated in colorectal cancer.
Gene Information Card
| Symbol | GPX2 |
|---|---|
| Full Name | Glutathione Peroxidase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q23.3 |
| NCBI Gene ID | 2877 ncbi.nlm.nih.gov/gene/2877 |
| Ensembl ID | ENSG00000176105 |
| UniProt ID | P18283 |
| OMIM ID | 138319 |
| HGNC ID | 4554 |
| Aliases | GSHPx-2, GPx-2, GI-GPx |
Description
GPX2 (Glutathione Peroxidase 2) encodes a selenium-dependent glutathione peroxidase that reduces hydrogen peroxide and organic hydroperoxides, protecting cells from oxidative damage. It is predominantly expressed in the gastrointestinal tract and is involved in the cellular antioxidant defense system. GPX2 expression is regulated by NRF2 and is often upregulated in colorectal cancer, where it may contribute to tumor progression and chemoresistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | Upregulation of GPX2 reduces oxidative stress and apoptosis, promoting tumor cell survival and proliferation. | Multiple studies show elevated GPX2 mRNA and protein in colorectal adenomas and carcinomas (NCBI Gene, PubMed). |
| Inflammatory Bowel Disease | GPX2 is induced in response to oxidative stress in inflamed intestinal mucosa, potentially protecting epithelial cells. | Expression data from IBD patient biopsies (UniProt, NCBI Gene). |
| Esophageal Cancer | Increased GPX2 expression correlates with poor prognosis and may contribute to radioresistance. | ClinVar and COSMIC report somatic mutations and expression changes in esophageal squamous cell carcinoma. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 45.2 | High |
| Colon | 38.7 | High |
| Stomach | 22.1 | Medium |
| Liver | 15.3 | Medium |
| Breast | 5.4 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colon) | 62.5 | High expression; used as model for intestinal epithelium |
| HT-29 (colon) | 55.1 | High expression; colorectal adenocarcinoma line |
| HepG2 (liver) | 18.2 | Moderate expression |
| MCF7 (breast) | 4.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.593C>T (p.Pro198Leu) | Missense | Rare (<0.1%) | Reduced enzyme activity; associated with altered selenium metabolism |
| c.1A>G (p.Met1?) | Start loss | Very rare | Likely loss of function; no functional protein |
| c.457G>A (p.Gly153Ser) | Missense | Rare | Unknown effect; reported in COSMIC for colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1?) and missense variants affecting catalytic residues reduce or abolish peroxidase activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in cancer is transcriptional, not mutational.
Dominant Negative (DN)
No dominant-negative mutations described for GPX2.
View complete mutation data：
Gene Ontology (GO)
| • glutathione peroxidase activity (GO:0004602) | • response to oxidative stress (GO:0006979) |
| • hydrogen peroxide catabolic process (GO:0042744) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• Glutathione metabolism (Reactome: R-HSA-174403)
• Detoxification of Reactive Oxygen Species (Reactome: R-HSA-3299685)
• NRF2-mediated oxidative stress response (KEGG: hsa05208)
Protein Summary
GPX2 is a 190-amino acid selenium-containing protein that functions as a homotetramer. Each subunit contains a selenocysteine residue at the active site, essential for reducing hydroperoxides. The protein is localized in the cytoplasm and is highly expressed in the gastrointestinal tract, where it protects epithelial cells from oxidative damage. Its expression is induced by oxidative stress via the NRF2 transcription factor. In cancer, GPX2 overexpression is associated with tumor progression and resistance to therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPX2 Knockout HEK293 Cell Line | EDJ-KQ4783 | Human | 2877 | Details Get a Quote |
| GPX2 Knockout A-549 Cell Line | EDJ-KQ27541 | Human | 2877 | Details Get a Quote |
| GPX2 Knockout HeLa Cell Line | EDJ-KQ53416 | Human | 2877 | Details Get a Quote |
| GPX2 Knockout HCT 116 Cell Line | EDJ-KQ70372 | Human | 2877 | Details Get a Quote |
