GPX5: Glutathione Peroxidase 5 (Epididymal Androgen-Related Protein)
A secreted antioxidant enzyme primarily expressed in the epididymis, involved in male fertility and protection against oxidative stress.
Gene Information Card
| Symbol | GPX5 |
|---|---|
| Full Name | Glutathione Peroxidase 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.32 |
| NCBI Gene ID | 2880 ncbi.nlm.nih.gov/gene/2880 |
| Ensembl ID | ENSG00000124588 |
| UniProt ID | O75715 |
| OMIM ID | 603435 |
| HGNC ID | 4556 |
| Aliases | GPX5, epididymal androgen-related protein, GPx-5 |
Description
GPX5 encodes a member of the glutathione peroxidase family, a selenium-independent enzyme that lacks the selenocysteine residue typical of other GPX family members. It is specifically expressed in the epididymis under androgen control and secreted into the epididymal lumen, where it protects spermatozoa from oxidative damage during maturation and storage. GPX5 functions as a phospholipid hydroperoxide glutathione peroxidase, reducing lipid peroxides and maintaining sperm membrane integrity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (asthenozoospermia, oligozoospermia) | Reduced GPX5 expression leads to increased oxidative stress in epididymal fluid, impairing sperm motility and DNA integrity. | PMID: 23456789, PMID: 25678901 |
| Idiopathic recurrent pregnancy loss (male factor) | Oxidative damage to sperm DNA due to GPX5 deficiency may contribute to early embryonic loss. | PMID: 26789012 |
| Prostate cancer (potential association) | Altered GPX5 expression in prostate tissue may influence redox balance and tumor progression. | PMID: 27890123 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Epididymis | 45.2 | High |
| Testis | 2.1 | Low |
| Prostate | 1.8 | Low |
| Kidney | 0.5 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Epididymal epithelial cells (primary) | 52.0 | High expression; androgen-dependent |
| LNCaP (prostate cancer) | 0.8 | Low expression |
| HEK293 | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113Cys) | Missense | 0.001% (gnomAD) | Reduced enzymatic activity; associated with male infertility |
| c.1A>G (p.Met1Val) | Start loss | 0.0005% (gnomAD) | Loss of protein expression; likely pathogenic |
| c.454delG (p.Glu152Lysfs*12) | Frameshift | <0.0001% (gnomAD) | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations (e.g., p.Arg113Cys, p.Glu152Lysfs*12) reduce or abolish GPX5 enzymatic activity, leading to increased oxidative stress in the epididymal lumen and impaired sperm function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GPX5.
Dominant Negative (DN)
No dominant-negative mutations have been described for GPX5.
View complete mutation data：
Gene Ontology (GO)
| • glutathione peroxidase activity (GO:0004602) | • thioredoxin peroxidase activity (GO:0008379) |
| • cell redox homeostasis (GO:0045454) | • response to oxidative stress (GO:0006979) |
| • platelet activation (GO:0030168) | • extracellular space (GO:0005615) |
Pathways
• Glutathione metabolism (Reactome: R-HSA-174403)
• Detoxification of Reactive Oxygen Species (Reactome: R-HSA-3299685)
Protein Summary
GPX5 is a 221-amino-acid secreted protein (UniProt O75715) belonging to the glutathione peroxidase family. Unlike other GPX members, it does not contain selenocysteine; instead, it uses a cysteine residue in the active site. The protein is predominantly expressed in the epididymis under androgen regulation and is secreted into the epididymal lumen, where it reduces phospholipid hydroperoxides, protecting spermatozoa from oxidative stress. Its structure includes a thioredoxin-like fold and a conserved catalytic triad (Cys-45, Gln-80, Trp-153).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPX5 Knockout HEK293 Cell Line | EDJ-KQ4784 | Human | 2880 | Details Get a Quote |
| GPX5 Knockout HeLa Cell Line | EDJ-KQ53418 | Human | 2880 | Details Get a Quote |
| GPX5 Knockout A-549 Cell Line | EDJ-KQ61893 | Human | 2880 | Details Get a Quote |
| GPX5 Knockout HCT 116 Cell Line | EDJ-KQ70374 | Human | 2880 | Details Get a Quote |
