GPX5
protein-codingglutathione peroxidase 5
Gene summary
This gene belongs to the glutathione peroxidase family. It is specifically expressed in the epididymis in the mammalian male reproductive tract, and is androgen-regulated. Unlike several other characterized glutathione peroxidases, this enzyme is not a selenoprotein, lacking the selenocysteine residue. Thus, it is selenium-independent, and has been proposed to play a role in protecting the membranes of spermatozoa from the damaging effects of lipid peroxidation and/or preventing premature acrosome reaction. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GPX5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001509.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 29 | 3 | 32 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 30 | 3 | 0 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001500.1 | 5 | MANE Select | |
| Ensembl | ENSP00000392398.2 | 5 | MANE Select | |
| RefSeq | NP_003987.2 | 3 | Standard | |
| Ensembl | ENSP00000419935.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Thyroid hormone synthesis - Homo sapiens (human)
- Glutathione metabolism - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- One carbon metabolism and related pathways
- Detoxification of Reactive Oxygen Species
Biological Process
- lipid metabolic process
- cellular response to oxidative stress
- oxidation-reduction process
- cellular oxidant detoxification
Molecular Function
- peroxidase activity
- glutathione peroxidase activity
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000412168
- Coding exons
- 5
- Length
- 9028
- Individuals with no LoFs
- 125682
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 55
- Defined
- 125737
- p
- 0.000219
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.245 | 109 | 116 | 0.936 | 0.00000603 | 1454 |
| Missense (PolyPhen) | 36 | 38.03 | 0.94663 | 503 | ||
| Synonymous | -0.214 | 48 | 46.1 | 1.04 | 0.00000261 | 411 |
| Loss of Function | 0.882 | 6 | 8.83 | 0.680 | 3.70e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0019 | 0.0019 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00019 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.745
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.162
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |