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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EPHX1
epoxide hydrolase 1
Chromosome 1 · 1q42.12
NCBI Gene: 2052Ensembl: ENSG00000143819.14HGNC: HGNC:3401UniProt: P07099
424PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
arachidonate metabolic processepoxide hydrolase activitycis-stilbene-oxide hydrolase activityepoxide metabolic processhypercholanemia, familial 1hypercholanemia, familialheart failureesophageal disease
✦AI Summary

EPHX1 (epoxide hydrolase 1) is a microsomal biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive dihydrodiols 1. The enzyme metabolizes endogenous lipids, including epoxide-containing fatty acids and the endocannabinoid 2-arachidonoylglycerol (2-AG), converting it to arachidonic acid and glycerol. EPHX1 possesses dual capability to either detoxify or bioactivate a broad range of substrates 1. In disease contexts, EPHX1 gene polymorphisms (Tyr113His and His139Arg) show ethnicity-dependent associations with cancer susceptibility. The Tyr113His homozygote genotype increases cancer risk in Asian populations 2, while the His139Arg polymorphism demonstrates a protective effect against colorectal cancer in Caucasians 3. EPHX1 variants are also associated with pre-eclampsia risk and chr1 obstructive pulmonary disease (COPD) susceptibility 45. Additionally, EPHX1 polymorphisms significantly influence carbamazepine metabolism in epilepsy patients, affecting drug concentrations and metabolite levels 6. Recent research identifies EPHX1 as a therapeutic target in pancreatic cancer, where its suppression through TRIM21-mediated degradation promotes tumor growth and chemotherapy resistance 7.

Sources cited
1
EPHX1 is a biotransformation enzyme that converts epoxides to diols and can detoxify or bioactivate substrates
PMID: 26216302
2
EPHX1 metabolizes arachidonic acid; TRIM21-mediated EPHX1 degradation promotes pancreatic cancer growth and gemcitabine resistance
PMID: 39739616
3
EPHX1 rs1051740 and rs2234922 polymorphisms are associated with pre-eclampsia risk in ethnicity-dependent manner
PMID: 33586574
4
EPHX1 Tyr113His homozygote increases cancer risk in Asian and mixed populations but not Caucasians
PMID: 25261893
5
EPHX1 variants are associated with COPD susceptibility
PMID: 21778810
6
EPHX1 His139Arg polymorphism has protective effect against colorectal cancer in Caucasians
PMID: 22928041
7
EPHX1 polymorphisms rs1051740 and rs2234922 significantly affect carbamazepine metabolism in epilepsy patients
PMID: 31650507
Disease Associationsⓘ20
hypercholanemia, familial 1Open Targets
0.40Weak
hypercholanemia, familialOpen Targets
0.37Weak
esophageal diseaseOpen Targets
0.31Weak
heart failureOpen Targets
0.31Weak
kidney diseaseOpen Targets
0.28Weak
ovarian dysfunctionOpen Targets
0.27Weak
mixed connective tissue diseaseOpen Targets
0.27Weak
hereditary lipodystrophyOpen Targets
0.27Weak
Insulin resistanceOpen Targets
0.19Weak
cystic fibrosisOpen Targets
0.19Weak
lipodystrophyOpen Targets
0.18Weak
chronic obstructive pulmonary diseaseOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
congenital heart diseaseOpen Targets
0.07Suggestive
polycystic ovary syndromeOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.05Suggestive
familial pseudohyperkalemiaOpen Targets
0.05Suggestive
adenomaOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_001136018.4(EPHX1):c.251G>A (p.Gly84Asp)Likely pathogenic
Hereditary lipodystrophy
★☆☆☆2024→ Residue 84
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Related Genes
EPHX2Protein interaction97%CYP2E1Protein interaction96%PTGES2Protein interaction95%GSTA1Protein interaction95%GSTA2Protein interaction95%CYP1A1Protein interaction95%
Tissue Expression6 tissues
Liver
100%
Ovary
31%
Brain
8%
Lung
8%
Heart
6%
Bone Marrow
5%
Gene Interaction Network
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EPHX1EPHX2CYP2E1PTGES2GSTA1GSTA2CYP1A1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P07099
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.85 [0.66–1.10]
RankingsWhere EPHX1 stands among ~20K protein-coding genes
  • #662of 20,598
    Most Researched424 · top 5%
  • #4,632of 5,498
    Most Pathogenic Variants1
  • #11,220of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedEPHX1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease.
PMID: 26216302
Gene · 2015
1.00
2
TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.
PMID: 39739616
Adv Sci (Weinh) · 2025
0.90
3
Oxidative stress-related genes (
PMID: 33586574
J Matern Fetal Neonatal Med · 2022
0.80
4
The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide sequence and structural characterization.
PMID: 7835893
Genomics · 1994
0.72
5
Quantitative assessment of the influence of EPHX1 gene polymorphisms and cancer risk: a meta-analysis with 94,213 subjects.
PMID: 25261893
J Exp Clin Cancer Res · 2014
0.70