GSTA4 Gene

HGNC Family	Glutathione S-transferases (GST)
Name	glutathione S-transferase alpha 4
Description	Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Glutathione S‐transferase A4 (GSTA4) is emerging as a critical enzyme for cellular defense against oxidative stress through its potent catalytic activity in detoxifying reactive lipid aldehydes, in particular 4‐hydroxynonenal (4‐HNE). GSTA4 is expressed in differentiated hepatic cells and is induced during liver regeneration by survival cytokines and growth factors, indicating its role in maintaining cellular homeostasis during rapid cellular turnover and stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its cytosolic presence, a mitochondrial pool of GSTA4 has been identified, supporting the enzyme’s involvement in shielding mitochondrial proteins from oxidative damage and protein carbonylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In adipocytes, decreased GSTA4 expression is associated with increased protein carbonylation, mitochondrial dysfunction, and insulin resistance, highlighting its importance in metabolic regulation under conditions of chronic oxidative stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, GSTA4 efficiently catalyzes the conjugation of 4‐HNE to glutathione, a reaction that prevents 4‐HNE from triggering pro‐apoptotic signaling events such as p53 induction and Fas activation. Overexpression of GSTA4 significantly blunts 4‐HNE–mediated apoptosis in retinal pigment epithelial cells and reduces cisplatin ototoxicity by preserving inner ear integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similar protective effects have been noted in endothelial cells, where enhanced GSTA4 expression leads to reduced aldehyde accumulation and a concomitant upregulation of defensive mediators such as inducible nitric oxide synthase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In prostate cancer cells, higher levels of GST A4 correlate with lower sensitivity to 4‐HNE–induced cytotoxicity, a phenomenon that is driven in part by transcriptional regulation through pathways such as those mediated by nuclear factor erythroid 2–related factor 2 (Nrf2)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, recent studies have implicated GSTA4 in diverse regulatory networks. In steroidogenic cells, for instance, the transcription factor SF‐1 directly controls the expression of the GSTA family, including GSTA4, suggesting a novel role in facilitating Δ(5)‐Δ(4) isomerization reactions in steroid hormone biosynthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, loss of the transcription factor KLF4 results in diminished Gsta4 expression and a subsequent accumulation of reactive oxygen species, reinforcing the concept that GSTA4 is pivotal for preventing oxidative DNA damage and maintaining genomic integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings position GSTA4 as an essential enzyme that not only detoxifies harmful lipid peroxidation products but also integrates signals from cytokine, growth factor, and redox‐sensitive pathways to preserve mitochondrial function, regulate cell survival, and modulate metabolic responses under stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Caroline Aninat, Amélie Piton, Denise Glaise, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.105.006759"}], "href": "https://doi.org/10.1124/dmd.105.006759"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16204462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16204462"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Fabienne Desmots, Mary Rissel, David Gilot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 and survival factor epidermal growth factor positively regulate the murine GSTA4 enzyme in hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112351200"}], "href": "https://doi.org/10.1074/jbc.M112351200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11884396"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11884396"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haider Raza, Marie-Anne Robin, Ji-Kang Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multiple isoforms of mitochondrial glutathione S-transferases and their differential induction under oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20020533"}], "href": "https://doi.org/10.1042/BJ20020533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12020353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12020353"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Colin T Shearn, Kristofer S Fritz, Alisabeth H Shearn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2015.11.013"}], "href": "https://doi.org/10.1016/j.redox.2015.11.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26654979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26654979"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jessica M Curtis, Paul A Grimsrud, Wendy S Wright, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db09-1105"}], "href": "https://doi.org/10.2337/db09-1105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20150287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20150287"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jie Li, Rajendra Sharma, Brad Patrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi060780+"}], "href": "https://doi.org/10.1021/bi060780+"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17014078"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17014078"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hyo-Jin Park, Mi-Jung Kim, Christina Rothenberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GSTA4 mediates reduction of cisplatin ototoxicity in female mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-12073-0"}], "href": "https://doi.org/10.1038/s41467-019-12073-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31515474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31515474"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yongzhen Yang, Yusong Yang, Ya Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial glutathione-S-transferase A4-4 protects against oxidative stress and modulates iNOS expression through NF-kappaB translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2008.03.018"}], "href": "https://doi.org/10.1016/j.taap.2008.03.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18485437"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18485437"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Larissa M Balogh, Isolde Le Trong, Kimberly A Kripps, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi902038u"}], "href": "https://doi.org/10.1021/bi902038u"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20085333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20085333"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Piergiorgio Pettazzoni, Eric Ciamporcero, Claudio Medana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Free Radic Biol Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.freeradbiomed.2011.07.009"}], "href": "https://doi.org/10.1016/j.freeradbiomed.2011.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21816220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21816220"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Takehiro Matsumura, Yoshitaka Imamichi, Tetsuya Mizutani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-222745"}], "href": "https://doi.org/10.1096/fj.12-222745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23650189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23650189"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Changchang Liu, Stephen La Rosa, Engda G Hagos "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for Krüppel-like factor 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.22161"}], "href": "https://doi.org/10.1002/mc.22161"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24788960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24788960"}]}]}]}
Synonyms	GSTA4-4, GTA4
Proteins	GSTA4_HUMAN
NCBI Gene ID	2941
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GSTA4 has 9,321 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 119 datasets.

Click the + buttons to view associations for GSTA4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GSTA4 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GSTA4 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GSTA4 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 GSTA4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GSTA4 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 GSTA4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GSTA4 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 GSTA4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of GSTA4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GSTA4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GSTA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GSTA4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GSTA4 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 GSTA4 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 GSTA4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GSTA4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GSTA4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GSTA4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GSTA4 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by GSTA4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GSTA4 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 GSTA4 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 GSTA4 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 GSTA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GSTA4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for GSTA4 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GSTA4 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 GSTA4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GSTA4 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 GSTA4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GSTA4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with GSTA4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GSTA4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.