Browse GPX4

Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform Mitochondrial: Mitochondrion ; SUBCELLULAR LOCATION: Isoform Cytoplasmic: Cytoplasm
Domain PF00255 Glutathione peroxidase
Function

Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385). 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).

> Gene Ontology
 
Biological Process GO:0006631 fatty acid metabolic process
GO:0006644 phospholipid metabolic process
GO:0006690 icosanoid metabolic process
GO:0006979 response to oxidative stress
GO:0009636 response to toxic substance
GO:0019372 lipoxygenase pathway
GO:0098754 detoxification
GO:0098869 cellular oxidant detoxification
GO:1990748 cellular detoxification
Molecular Function GO:0004601 peroxidase activity
GO:0004602 glutathione peroxidase activity
GO:0016209 antioxidant activity
GO:0016684 oxidoreductase activity, acting on peroxide as acceptor
GO:0047066 phospholipid-hydroperoxide glutathione peroxidase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa00480 Glutathione metabolism
Reactome R-HSA-2142753: Arachidonic acid metabolism
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-2142712: Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-2142770: Synthesis of 15-eicosatetraenoic acid derivatives
R-HSA-2142688: Synthesis of 5-eicosatetraenoic acids
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between GPX4 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between GPX4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29515790Hepatocellular CarcinomaPromote immunity (T cell function)GPx4-overexpressing cells displayed impaired tumor growth, reduced proliferation, altered angiogenesis and decreased expression of clinically relevant cytokine interleukin-8 and C-reactive protein. Moreover, GPx4 overexpression impaired migration of endothelial cells in vitro, and enhanced expression of thrombospondin 1, an endogenous inhibitor of angiogenesis. In patients, GPx4 expression in tumors positively correlated with survival and was linked to pathways which regulate cell proliferation, motility, tissue remodelling, immune response and M1 macrophage polarization.
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of GPX4 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.36; FDR: 0.04630 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -2.65; FDR: 0.02150 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of GPX4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1570.636
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.4410.904
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0490.985
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2680.6
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1030.966
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.7410.816
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1840.677
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.4040.835
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0080.997
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.2860.92
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.3850.929
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1320.0412
> Mutation difference between responders and non-responders
 

There is no record.
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GPX4. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GPX4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GPX4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GPX4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of GPX4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between GPX4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolGPX4
Nameglutathione peroxidase 4
Aliases PHGPx; phospholipid hydroperoxidase; glutathione peroxidase 4 (phospholipid hydroperoxidase); GPx-4; GSHPx-4 ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting GPX4 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting GPX4.
ID Name Drug Type Targets #Targets
DB00143GlutathioneSmall MoleculeAKR1B1, CYP3A4, ESD, GGT1, GLO1, GLRX, GLRX2, GPX1, GPX2, GPX3, GP ......41