EPHX2 Gene

HGNC Family	Phosphatases
Name	epoxide hydrolase 2, cytoplasmic
Description	This gene encodes a member of the epoxide hydrolase family. The protein, found in both the cytosol and peroxisomes, binds to specific epoxides and converts them to the corresponding dihydrodiols. Mutations in this gene have been associated with familial hypercholesterolemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The EPHX2 gene encodes soluble epoxide hydrolase (sEH), a bifunctional enzyme that principally converts epoxyeicosatrienoic acids (EETs)—potent vasodilatory, anti‐inflammatory, and cytoprotective lipid mediators produced by cytochrome P450 epoxygenases—from their active epoxide forms into less active diols. Through this catalytic activity, sEH modulates the bioavailability of EETs and thereby influences a wide range of biological processes, including vascular tone regulation, endothelial function, inflammatory responses, and metabolic as well as neuroprotective signaling.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic variations in EPHX2, such as non‐synonymous polymorphisms (for example, the K55R variant), have been associated with increased enzyme activity and with heightened risks for coronary heart disease and ischemic stroke in select populations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In experimental models, enhanced sEH activity has been linked to impaired endothelial function, elevated blood pressure, and increased vascular and renal inflammation, whereas genetic deletion or pharmacological inhibition of sEH elevates EET levels. Such manipulations improve insulin signaling, attenuate hypertensive renal injury, and reduce inflammatory responses to endotoxin."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, studies have shown that reduced sEH activity confers reno‐protective effects in hypertensive or diabetic contexts, with sEH inhibition leading to decreased renal inflammation, reduced albuminuria, and improved endothelial function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the central nervous system, genetic variants that enhance sEH activity have been associated with increased neuronal damage during ischemia, whereas those that lower hydrolase activity appear neuroprotective."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, vascular function studies in humans have linked EPHX2 polymorphisms not only to altered endothelial-dependent vasodilation but also to changes in forearm blood flow responses, underscoring sEH’s role in regulating vascular tone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Epidemiological investigations further support the notion that multiple variants within or near EPHX2 contribute differentially to the risk of ischemic stroke, with some haplotypes associating with increased incidence and others with protection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that EPHX2—and its encoded enzyme sEH—plays a central role in modulating EET-mediated signaling pathways that govern vascular homeostasis, inflammation, metabolic regulation, and tissue protection. Variations in EPHX2 can thereby influence susceptibility to cardiovascular and cerebrovascular diseases, and strategies that target sEH activity (either through gene disruption or inhibition) hold promise for therapeutic intervention in a range of pathophysiological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Craig R Lee, Kari E North, Molly S Bray, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddl085"}], "href": "https://doi.org/10.1093/hmg/ddl085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16595607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16595607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ayala Luria, Ahmed Bettaieb, Yannan Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble epoxide hydrolase deficiency alters pancreatic islet size and improves glucose homeostasis in a model of insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1103482108"}], "href": "https://doi.org/10.1073/pnas.1103482108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21571638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21571638"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ayala Luria, Steven M Weldon, Alisa K Kabcenell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M608057200"}], "href": "https://doi.org/10.1074/jbc.M608057200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17135253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17135253"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yangmei Deng, Matthew L Edin, Katherine N Theken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.10-171488"}], "href": "https://doi.org/10.1096/fj.10-171488"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21059750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21059750"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marlina Manhiani, Jeffrey E Quigley, Sarah F Knight, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00098.2009"}], "href": "https://doi.org/10.1152/ajprenal.00098.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19553349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19553349"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ahmed A Elmarakby, Jessica Faulkner, Mohammed Al-Shabrawey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.00759.2010"}], "href": "https://doi.org/10.1152/ajpregu.00759.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21832210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21832210"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ines P Koerner, Rachel Jacks, Andrea E DeBarber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to neuronal survival after ischemic injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0056-07.2007"}], "href": "https://doi.org/10.1523/JNEUROSCI.0056-07.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17460077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17460077"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Craig R Lee, Mias Pretorius, Robert N Schuck, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with forearm vasodilator responses in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.110.161695"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.110.161695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21098312"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21098312"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Myriam Fornage, Craig R Lee, Peter A Doris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi315"}], "href": "https://doi.org/10.1093/hmg/ddi315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16115816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16115816"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Andreas Gschwendtner, Stephan Ripke, Tobias Freilinger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an increased risk of ischemic stroke in white Europeans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.107.502179"}], "href": "https://doi.org/10.1161/STROKEAHA.107.502179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18323494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18323494"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Cristiano Fava, Martina Montagnana, Elisa Danese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0b013e3283349ec9"}], "href": "https://doi.org/10.1097/FPC.0b013e3283349ec9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20065888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20065888"}]}]}]}
Synonyms	SEH
Proteins	HYES_HUMAN
NCBI Gene ID	2053
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EPHX2 has 7,790 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 131 datasets.

Click the + buttons to view associations for EPHX2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving EPHX2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EPHX2 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 EPHX2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EPHX2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EPHX2 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 EPHX2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EPHX2 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 EPHX2 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 EPHX2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EPHX2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EPHX2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EPHX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EPHX2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EPHX2 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 EPHX2 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 EPHX2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EPHX2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EPHX2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EPHX2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EPHX2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EPHX2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for EPHX2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 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 EPHX2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EPHX2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for EPHX2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EPHX2 gene from the ENCODE Histone Modification Site Profiles dataset.