GPX8: Glutathione Peroxidase 8 – A Key Player in Redox Homeostasis and Cancer
Comprehensive genomic, transcriptomic, and proteomic overview of GPX8 (Glutathione Peroxidase 8) with curated data from NCBI, Ensembl, UniProt, OMIM, HGNC, COSMIC, and ClinVar.
Gene Information Card
| Symbol | GPX8 |
|---|---|
| Full Name | Glutathione Peroxidase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q11.2 |
| NCBI Gene ID | 493869 ncbi.nlm.nih.gov/gene/493869 |
| Ensembl ID | ENSG00000164294 |
| UniProt ID | Q8TED1 |
| OMIM ID | 611620 |
| HGNC ID | 24986 |
| Aliases | GPx-8, GSHPx-8, FLJ30655 |
Description
GPX8 (Glutathione Peroxidase 8) encodes a member of the glutathione peroxidase family that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides using glutathione as a reducing agent. Unlike classical GPXs, GPX8 is a non-selenocysteine-containing peroxidase localized to the endoplasmic reticulum, where it modulates oxidative protein folding and protects against ER stress. GPX8 is implicated in cancer progression, particularly in breast and lung cancers, and in cardiovascular diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | GPX8 overexpression promotes tumor growth and metastasis by reducing oxidative stress and enhancing ER protein folding. | COSMIC; PMID: 31570879 |
| Lung adenocarcinoma | GPX8 upregulation correlates with poor prognosis and resistance to chemotherapy via modulation of redox balance. | COSMIC; PMID: 32561859 |
| Cardiovascular diseases | GPX8 deficiency exacerbates oxidative stress and endothelial dysfunction in animal models. | OMIM 611620; PMID: 29212778 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Breast | 8.3 | Low |
| Lung | 15.7 | Medium |
| Liver | 6.2 | Low |
| Kidney | 9.1 | Low |
| Heart | 4.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 18.4 | High expression; associated with ER stress response |
| A549 (lung cancer) | 22.1 | High expression; linked to chemoresistance |
| HepG2 (liver cancer) | 7.2 | Moderate expression |
| HEK293 (embryonic kidney) | 5.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113Trp) | Missense | 0.02% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.488G>A (p.Arg163Gln) | Missense | 0.01% (gnomAD) | Unknown; predicted benign |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Val) are predicted to abolish protein translation, leading to complete loss of GPX8 activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in literature or curated databases.
Dominant Negative (DN)
No evidence of dominant-negative effects for GPX8 variants.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glutathione metabolism (Reactome: R-HSA-174403)
• Detoxification of Reactive Oxygen Species (Reactome: R-HSA-3299685)
• Unfolded Protein Response (UPR) (Reactome: R-HSA-381119)
Protein Summary
GPX8 is a 251-amino-acid protein (UniProt Q8TED1) localized to the endoplasmic reticulum. It contains a thioredoxin-like fold and a conserved catalytic triad (Cys, Gln, Trp) but lacks selenocysteine, distinguishing it from classical GPXs. GPX8 reduces H2O2 and organic hydroperoxides using glutathione, protecting cells from oxidative damage during ER protein folding. Its expression is induced by ER stress and is frequently upregulated in cancers, where it supports tumor survival under oxidative conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPX8 Knockout HEK293 Cell Line | EDJ-KQ11919 | Human | 493869 | Details Get a Quote |
| GPX8 Knockout A-549 Cell Line | EDJ-KQ40404 | Human | 493869 | Details Get a Quote |
| GPX8 Knockout HCT 116 Cell Line | EDJ-KQ40405 | Human | 493869 | Details Get a Quote |
| GPX8 Knockout HeLa Cell Line | EDJ-KQ40406 | Human | 493869 | Details Get a Quote |
