GPX4
Chr 19ARglutathione peroxidase 4
Also known as: GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx, snPHGPx
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. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). 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. Transcript variants resulting from alternative splicing or use of alternate promoters have been described to encode isoforms with different subcellular localization. [provided by RefSeq, Dec 2018]
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
235 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 6 | 0 | 2 | 0 | 8 |
Likely Pathogenic | 8 | 1 | 0 | 0 | 9 |
VUS | 1 | 86 | 4 | 1 | 92 |
Likely Benign | 0 | 11 | 42 | 30 | 83 |
Benign | 0 | 1 | 20 | 5 | 26 |
Conflicting | — | 4 | |||
| Total | 15 | 99 | 68 | 36 | 222 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →32 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap GPX4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
GPX4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Outer Membrane Vesicle and Ferroptosis-Related Signatures in Sepsis-Associated Acute Lung Injury Caused by Extra-Pulmonary Hypervirulent Klebsiella Pneumoniae
NOT YET RECRUITINGMarkers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach
ACTIVE NOT RECRUITINGA Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of SNP-610 for the Treatment of Patients With Non-alcoholic Steatohepatitis
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools