GPX3 Gene

Name	glutathione peroxidase 3
Description	The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, 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 is secreted, and is abundantly found in plasma. Downregulation of expression of this gene by promoter hypermethylation has been observed in a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia. 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Glutathione peroxidase 3 (GPx3) is a selenium‐dependent extracellular antioxidant enzyme that plays a central role in detoxifying reactive oxygen species and thereby protecting cells and tissues from oxidative damage. In the context of cancer, loss or epigenetic inactivation of GPx3 has been associated with tumor progression and poor clinical outcome. For example, in prostate cancer, frequent deletion and promoter hypermethylation of the GPx3 gene correlate with reduced GPx3 expression, increased invasiveness, and metastatic behavior, supporting its function as a tumor suppressor by down‐regulating oncogenic signals such as c‐met."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In metabolic tissues, GPx3 contributes to redox homeostasis by counteracting the deleterious effects of inflammatory and pro‐oxidative signals. In adipose tissue, reduced GPx3 expression is linked to elevated local oxidative stress that fosters inflammation and insulin resistance, whereas its overexpression improves high‐glucose–induced insulin resistance and diminishes inflammatory gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in skeletal muscle, GPx3 induction via peroxisome proliferator–activated receptor γ activation or estrogen receptor signaling lowers extracellular hydrogen peroxide levels, thereby enhancing insulin signaling and improving glucose uptake."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the vascular compartment, GPx3 contributes to the maintenance of endothelial function and limits platelet activation; its deficiency leads to a prothrombotic state marked by increased platelet aggregation and endothelial dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in the gastrointestinal tract, GPx3 is frequently silenced via promoter hypermethylation during Barrett’s carcinogenesis, suggesting that the loss of its antioxidant activity may facilitate oxidative damage and disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Likewise, GPx3 methylation in various malignancies, including head and neck cancers, is associated with chemoresistance, further emphasizing its role in counteracting oxidative stress and modulating tumor response to treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies support a model in which GPx3 serves as a pivotal extracellular antioxidant that not only safeguards genomic and cellular integrity against oxidative insults but also modulates critical signaling pathways in cancer, metabolism, and vascular homeostasis. Targeting GPx3 expression or function may thus represent a promising strategy in the prevention and treatment of oxidative stress–related diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yan P Yu, Guoying Yu, George Tseng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-07-0648"}], "href": "https://doi.org/10.1158/0008-5472.CAN-07-0648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17804715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17804715"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yun Sok Lee, A Young Kim, Jin Woo Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2008-0023"}], "href": "https://doi.org/10.1210/me.2008-0023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18562625"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18562625"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sung Soo Chung, Min Kim, Byoung-Soo Youn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00544-08"}], "href": "https://doi.org/10.1128/MCB.00544-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18936159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18936159"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Richard C Jin, Christopher E Mahoney, Laura Coleman Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutathione peroxidase-3 deficiency promotes platelet-dependent thrombosis in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.110.000034"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.110.000034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21518981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21518981"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ok-Jae Lee, Regine Schneider-Stock, Patricia A McChesney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation and loss of expression of glutathione peroxidase-3 in Barrett's tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.05328"}], "href": "https://doi.org/10.1593/neo.05328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16229808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16229808"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Baishen Chen, Xi Rao, Michael G House, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPx3 promoter hypermethylation is a frequent event in human cancer and is associated with tumorigenesis and chemotherapy response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2011.05.013"}], "href": "https://doi.org/10.1016/j.canlet.2011.05.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21684681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21684681"}]}]}]}
Synonyms	GSHPX-3, GSHPX-P, GPX-P
Proteins	GPX3_HUMAN
NCBI Gene ID	2878
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GPX3 has 15,514 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for GPX3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GPX3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by GPX3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPX3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPX3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GPX3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GPX3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GPX3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GPX3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GPX3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GPX3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GPX3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GPX3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GPX3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GPX3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GPX3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GPX3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GPX3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GPX3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GPX3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GPX3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GPX3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GPX3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GPX3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GPX3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GPX3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GPX3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GPX3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GPX3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GPX3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GPX3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GPX3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GPX3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GPX3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GPX3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GPX3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for GPX3 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GPX3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GPX3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GPX3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GPX3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GPX3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.