GPX4

Chr 19AR

glutathione peroxidase 4

Also known as: GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx, snPHGPx

The protein is an essential antioxidant peroxidase that directly reduces phospholipid hydroperoxides in membranes and lipoproteins, protecting cells from oxidative damage and preventing ferroptosis (iron-dependent cell death). Mutations cause spondylometaphyseal dysplasia, Sedaghatian type, a severe skeletal dysplasia with autosomal recessive inheritance. This gene shows minimal constraint against loss-of-function variants (pLI 0.00005, LOEUF 1.28), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.281 OMIM phenotype
Clinical SummaryGPX4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.000
Z-score 0.91
OE 0.71 (0.411.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.08Z-score
OE missense 1.27 (1.121.45)
159 obs / 125.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.411.28)
00.351.4
Missense OE1.27 (1.121.45)
00.61.4
Synonymous OE1.59
01.21.6
LoF obs/exp: 8 / 11.3Missense obs/exp: 159 / 125.2Syn Z: -3.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGPX4-related spondylometaphyseal dysplasia, Sedaghatian typeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.6541th %ile
LOF
0.2679th %ile

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPX4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗