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GPX4

Chr 19p13.3

glutathione peroxidase 4

Aliases:
PHGPx, MCSP
MANE:
ENST00000354171.13

Annotations refreshed 9 hours ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • DDG2P

    BIALLELIC, autosomal or pseudoautosomal
  • Fetal anomalies

    BIALLELIC, autosomal or pseudoautosomal
  • Skeletal dysplasia

    BIALLELIC, autosomal or pseudoautosomal
  • Familial Meniere Disease

Disease associations (Open Targets)

  • spondylometaphyseal dysplasia, Sedaghatian type

    0.72
  • neurodegenerative disease

    0.47
  • nasal cavity polyp

    0.30
  • chronic rhinosinusitis with nasal polyps

    0.30
  • basal cell carcinoma

    0.28
  • skin cancer

    0.26
  • skin neoplasm

    0.24
  • hypothyroidism

    0.22
  • hereditary disease

    0.20
  • hemolysis

    0.18

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Phospholipid hydroperoxide glutathione peroxidase GPX4

Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (PubMed:40281343). Can also reduce cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:40281343). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385, PubMed:40281343). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (PubMed:11115402). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down-regulator of the cellular 15-lipoxygenase pathway (By similarity). Can reduce fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). Can also reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide (PubMed:17630701, PubMed:36608588)

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.