EPHX2 (Epoxide Hydrolase 2): Gene Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the EPHX2 gene, encoding soluble epoxide hydrolase, with emphasis on its role in cardiovascular, renal, and inflammatory diseases, as well as its potential as a therapeutic target.
Gene Information Card
| Symbol | EPHX2 |
|---|---|
| Full Name | Epoxide Hydrolase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p21.2 |
| NCBI Gene ID | 2053 ncbi.nlm.nih.gov/gene/2053 |
| Ensembl ID | ENSG00000120915 |
| UniProt ID | P34913 |
| OMIM ID | 132811 |
| HGNC ID | 3402 |
| Aliases | sEH, ABHD9, MMSDH, sEHc, sEHm |
Description
The EPHX2 gene encodes soluble epoxide hydrolase (sEH), a bifunctional enzyme involved in the metabolism of xenobiotics and endogenous lipid signaling molecules. sEH primarily catalyzes the hydrolysis of epoxide-containing fatty acids, such as epoxyeicosatrienoic acids (EETs), to their corresponding diols (dihydroxyeicosatrienoic acids, DHETs). EETs are potent mediators with anti-inflammatory, vasodilatory, and cardioprotective effects; thus, sEH activity modulates these physiological processes. The enzyme also possesses lipid phosphatase activity. EPHX2 is expressed in various tissues, with high levels in the liver, kidney, and vascular endothelium. Genetic variants in EPHX2 have been associated with susceptibility to cardiovascular diseases, including hypertension and coronary artery disease, as well as chronic kidney disease and inflammatory conditions. Consequently, sEH inhibitors are being investigated as therapeutic agents for these diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular disease | Altered sEH activity affects EET levels, influencing vascular tone and inflammation. Polymorphisms may increase risk. | Association studies (e.g., PMID: 15199031, 17634422) |
| Hypertension | Reduced EET bioavailability due to increased sEH activity can lead to elevated blood pressure. Variants may affect enzyme activity. | Genetic association studies (e.g., PMID: 15611362, 19074825) |
| Chronic kidney disease | sEH modulates renal blood flow and inflammation; dysregulation contributes to renal fibrosis and progression. | Experimental models and human studies (e.g., PMID: 22009144, 24676617) |
| Stroke | EETs are neuroprotective; increased sEH activity may exacerbate ischemic injury. | Case-control studies (e.g., PMID: 17502553) |
| Inflammatory diseases | sEH regulates inflammation via EET metabolism; altered activity may influence inflammatory responses. | Preclinical studies (e.g., PMID: 20876742) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 72.3 | High |
| Kidney | 61.8 | High |
| Adrenal gland | 45.2 | High |
| Lung | 20.1 | Medium |
| Heart | 15.4 | Medium |
| Brain | 8.7 | Low |
| Skeletal muscle | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 58.4 | Hepatocellular carcinoma cell line |
| A549 | 22.3 | Lung carcinoma cell line |
| HEK293 | 12.1 | Embryonic kidney cells |
| HUVEC | 18.7 | Human umbilical vein endothelial cells |
| THP-1 | 9.8 | Monocytic leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R287Q | Missense | ~5% in some populations | Reduced enzyme activity, associated with altered EET metabolism |
| K55R | Missense | ~10% in some populations | May affect enzyme stability or activity; conflicting reports |
| C184Y | Missense | Rare | Loss of function, associated with familial hypercholanemia |
| R103C | Missense | Rare | Loss of function, linked to familial hypercholanemia |
Mutation functional classification
Loss of Function (LOF)
Mutations such as C184Y and R103C result in reduced or absent sEH activity, leading to accumulation of EETs and potential metabolic disturbances.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; some variants may increase activity but evidence is limited.
Dominant Negative (DN)
Not well established; some missense variants may exert dominant-negative effects by forming inactive dimers, but this requires further investigation.
View complete mutation data：
Gene Ontology (GO)
| • epoxide hydrolase activity | • lipid phosphatase activity |
| • hydrolase activity | • protein homodimerization activity |
| • metal ion binding | • response to xenobiotic stimulus |
| • epoxygenase P450 pathway | • lipid metabolic process |
| • inflammatory response | • vasodilation |
Pathways
• Arachidonic acid metabolism
• Epoxyeicosatrienoic acid (EET) metabolism
• Xenobiotic metabolism
• PPAR signaling pathway
• VEGF signaling pathway
Protein Summary
Soluble epoxide hydrolase (sEH) is a homodimeric enzyme with two distinct catalytic domains: an N-terminal lipid phosphatase domain and a C-terminal epoxide hydrolase domain. The epoxide hydrolase domain catalyzes the conversion of epoxides to diols, with high affinity for EETs, which are signaling lipids derived from arachidonic acid. By degrading EETs, sEH regulates their anti-inflammatory, vasodilatory, and pro-fibrinolytic effects. The lipid phosphatase activity may regulate cholesterol metabolism and other lipid signaling. sEH is expressed in many tissues, particularly liver, kidney, and vasculature. Its activity is modulated by genetic variants, oxidative stress, and pharmacological inhibitors, making it a promising target for treating hypertension, chronic kidney disease, and inflammatory disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPHX2 Knockout HEK293 Cell Line | EDJ-KQ4549 | Human | 2053 | Details Get a Quote |
| EPHX2 Knockout HeLa Cell Line | EDJ-KQ25922 | Human | 2053 | Details Get a Quote |
| EPHX2 Knockout A-549 Cell Line | EDJ-KQ27180 | Human | 2053 | Details Get a Quote |
| EPHX2 Knockout HCT 116 Cell Line | EDJ-KQ27181 | Human | 2053 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
