GPX6
protein-codingglutathione peroxidase 6, 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 hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. Expression of this gene has been observed in embryos and olfactory epithelium; however, the exact function of this gene is not known. This isozyme is a selenoprotein in humans, 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. The orthologs of this gene in mouse and rat (and some other species) contain a cysteine (Cys) residue in place of the Sec residue, and their corresponding mRNAs lack SECIS element. [provided by RefSeq, Jul 2017]
- GPXP3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.9 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 GPX6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182701.1. 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 | 28 | 2 | 30 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 28 | 0 | 2 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_874360.1 | 5 | MANE Select | |
| Ensembl | ENSP00000354581.1 | 5 | MANE Select | |
| Ensembl | ENSP00000417364.1 | 4 | Standard | |
| Ensembl | ENSP00000417364.1 | 4 | 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)
- Selenium Micronutrient Network
- Folate Metabolism
Biological Process
- 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
- ENST00000361902
- Coding exons
- 5
- Length
- 24920
- Individuals with no LoFs
- 125020
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125037
- p
- 0.0000680
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.474 | 100 | 114 | 0.875 | 0.00000549 | 1452 |
| Missense (PolyPhen) | 22 | 33.05 | 0.66566 | 461 | ||
| Synonymous | 2.10 | 29 | 47.4 | 0.612 | 0.00000257 | 412 |
| Loss of Function | 0.271 | 9 | 9.92 | 0.907 | 4.18e-7 | 121 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Intolerance Scores
- LoFtool
- 0.728
- RVIS EVS
- 1.77
- RVIS percentile EVS
- 96.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.000296
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |