GPX3
protein-codingglutathione peroxidase 3, the group of Selenoproteins
Gene summary
The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme is secreted, and is abundantly found in plasma. Downregulation of expression of this gene by promoter hypermethylation has been observed in a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia. This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.4 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 GPX3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002084.5. 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 | 0 | |||||
| missense | 30 | 30 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 32 | 0 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002075.2 | 5 | MANE Select | |
| Ensembl | ENSP00000373477.4 | 5 | MANE Select | |
| RefSeq | NP_001316719.1 | 6 | Standard | |
| Ensembl | ENSP00000429709.1 | 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)
- Glutathione metabolism
- Selenium Micronutrient Network
Biological Process
- response to lipid hydroperoxide
- cellular response to oxidative stress
- hydrogen peroxide catabolic process
- protein homotetramerization
- oxidation-reduction process
Molecular Function
- peroxidase activity
- glutathione peroxidase activity
- protein binding
- transcription factor binding
- selenium binding
Cellular Component
- extracellular region
- extracellular space
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000388825
- Coding exons
- 5
- Length
- 8431
- Individuals with no LoFs
- 124822
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 124863
- p
- 0.000164
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.566 | 114 | 132 | 0.862 | 0.00000747 | 1464 |
| Missense (PolyPhen) | 58 | 62.709 | 0.9249 | 686 | ||
| Synonymous | -0.150 | 57 | 55.6 | 1.03 | 0.00000332 | 451 |
| Loss of Function | 2.04 | 4 | 11.4 | 0.350 | 5.72e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00043 | 0.00042 | 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.;
Intolerance Scores
- LoFtool
- 0.640
- RVIS EVS
- -0.43
- RVIS percentile EVS
- 25.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.233
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |