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FLASH GENE
Symbol GPX4 contributors: mct/npt/pgu - updated : 24-09-2019
HGNC name glutathione peroxidase 4 (phospholipid hydroperoxidase)
HGNC id 4556
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Gpx4
Homologene
FAMILY
  • glutathione peroxidase family
  • selenium-dependent glutathione peroxidases family
  • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    intracellular,nuclear envelope
    text
  • at least three isoforms in testis: cytosolic, mitochondrial and nuclear
  • nuclear form of GPX4 has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome
  • basic FUNCTION
  • glutathione peroxidase, free radical detoxification, catabolic pathway of activated oxygen species, oxydoreductase
  • catalyzing the reduction of hydrogen peroxide, organic hydroperoxide, and lipid peroxides by reduced glutathione and functions in the protection of cells against oxidative damage
  • playing an indispensable role for structural integrity of spermatozoa and to codetermine sperm motility and viability
  • playing a pivotal role in brain development and function
  • multifunctional and it acts as a reducing enzyme of peroxidized phospholipids and thiols and as a structural protein
  • essential antioxidant enzyme having multiple functions
  • GPX5 protein, and the epithelial proteins GPX1, GPX3, and cellular GPX4, all functioning in the mammalian epididymis at different stages of the sperm epididymal journey, and in different epididymis compartments
  • nuclear form of GPX4 is associated with sperm nuclear matrix and is required for proper paternal chromatin decondensation at fertilization
  • GPX4 is a critical antioxidant enzyme for the maturation and survival of photoreceptor cells
  • is essential for maintaining oxidative homeostasis and keeping defense against oxidative stress in conjunctival epithelial cells
  • antioxidant defense enzyme active in repairing oxidative damage to lipids, that is a key inhibitor of ferroptosis, a non-apoptotic form of cell death involving lipid reactive oxygen species
  • ferroptosis inhibition by GPX4 is essential for motor neuron health and survival
  • is an important antioxidant enzyme for maintaining redox status and protecting corneal endothelial cells from oxidative stress
  • is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids
  • paternal acetylated histones and acrosomal nuclear GPX4 are directly involved in fertilization
  • antioxidant enzyme, having biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids
  • GPX4 regulates reactive oxygen species-induced cell death
  • ferroptosis is mediated by the accumulation of lipid peroxides upon the depletion/or inhibition of glutathione peroxidase 4 (GPX4)
  • unique antioxidant enzyme that can directly reduce phospholipid hydroperoxide
  • increased lipid peroxidation resulting from reduced GPX4 expression levels may be causally associated with lung fibrosis development
  • GPX1 and GPX4 dampen phosphorylation cascades predominantly via prevention of inactivation of phosphatases by H2O2 or lipid hydroperoxides
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS detoxification
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    fatty acid
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GRSF1 up-regulates translation of GPX4 mRNA and implicate the two proteins in embryonic brain development
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HXALI , SMDS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in blood of women with preeclampsia
    constitutional     --low  
    significant reductions in expression of GPX1, GPX3, GPX4 in placentae from women with preeclampsia
    Susceptibility
  • to sterility and infertility
  • to cardiovascular autonomic neuropathy in individuals with type 1 diabetes
  • to Preeclampsia (PE)
  • Variant & Polymorphism other
  • functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes
  • rs713041 in GPX4 may play a key role in the pathogenesis of PE
  • Candidate gene
  • is a possible candidate susceptibility gene for Kashin-Beck disease (KBD)
  • Marker
  • GPX4 and GPX7 are possible markers for improving Hepatocellular carcinoma (HCC) diagnosis/prognosis
  • overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma
  • Therapy target
    ANIMAL & CELL MODELS
  • spermatozoa of mice lacking both the sperm nucleus glutathione peroxidase 4 (snGPx4) and the epididymal glutathione peroxidase 5 (GPx5) activities display sperm nucleus structural abnormalities including delayed and defective nuclear compaction, nuclear instability and DNA damage