EPHX4 (Epoxide Hydrolase 4): A Key Player in Xenobiotic Metabolism and Disease
Explore the genomic, proteomic, and clinical significance of EPHX4, including its role in detoxification, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | EPHX4 |
|---|---|
| Full Name | Epoxide Hydrolase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 23252 ncbi.nlm.nih.gov/gene/23252 |
| Ensembl ID | ENSG00000116285 |
| UniProt ID | Q9H6B9 |
| OMIM ID | 613358 |
| HGNC ID | 23775 |
| Aliases | ABHD7, EPHX4, epoxide hydrolase 4 |
Description
EPHX4 encodes epoxide hydrolase 4, an enzyme belonging to the epoxide hydrolase family. These enzymes catalyze the hydrolysis of epoxides (reactive electrophiles) into diols, playing a crucial role in detoxification of xenobiotics and endogenous metabolites. EPHX4 is expressed in various tissues, with highest levels in the liver and kidney, and is involved in lipid metabolism and cellular signaling. Mutations in EPHX4 have been linked to certain cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression and mutations may affect detoxification of carcinogenic epoxides, leading to DNA damage and tumorigenesis. | COSMIC database lists somatic mutations in EPHX4 across multiple cancer types. |
| Metabolic syndrome | Potential role in lipid metabolism; dysregulation may contribute to metabolic disturbances. | Expression studies show correlation with lipid metabolism genes; further research needed. |
| Liver disease | Reduced EPHX4 activity may impair detoxification, increasing susceptibility to hepatotoxicity. | Expression in liver; functional studies in animal models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (e.g., 50-100 nTPM) | Highest expression |
| Kidney | Moderate (e.g., 20-50 nTPM) | Significant expression |
| Lung | Low to moderate (e.g., 10-20 nTPM) | Detectable |
| Brain | Low (e.g., <10 nTPM) | Minimal expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | High | Consistent with liver expression |
| A549 (lung cancer) | Moderate | Detectable expression |
| HEK293 (embryonic kidney) | Moderate | Expressed |
| MCF7 (breast cancer) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113Ter) | Nonsense | Rare (<0.1%) | Loss of function; truncated protein |
| c.556G>A (p.Gly186Arg) | Missense | Somatic in cancer (COSMIC) | Potential functional impact; unknown |
| c.784A>G (p.Thr262Ala) | Missense | Rare (<0.1%) | Possibly benign; not characterized |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations leading to premature stop codons result in truncated, non-functional protein, reducing epoxide hydrolase activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations reported in EPHX4.
Dominant Negative (DN)
No evidence of dominant-negative effects; EPHX4 likely functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
| • epoxide hydrolase activity | • hydrolase activity |
| • lipid metabolic process | • xenobiotic metabolic process |
| • cellular response to xenobiotic stimulus |
Pathways
• Epoxide metabolism
• Xenobiotic detoxification
• Lipid metabolism
Protein Summary
EPHX4 is a 55 kDa protein with an alpha/beta hydrolase fold. It is localized to the endoplasmic reticulum and cytosol. The enzyme catalyzes the conversion of epoxides to diols, using water as a co-substrate. It plays a role in detoxifying reactive epoxides derived from environmental pollutants and endogenous lipid peroxidation. EPHX4 also participates in the metabolism of fatty acid epoxides, influencing inflammation and cell proliferation. Its expression is regulated by nuclear receptors such as AhR and Nrf2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPHX4 Knockout HEK293 Cell Line | EDJ-KQ11729 | Human | 253152 | Details Get a Quote |
| EPHX4 Knockout A-549 Cell Line | EDJ-KQ40093 | Human | 253152 | Details Get a Quote |
| EPHX4 Knockout HCT 116 Cell Line | EDJ-KQ40094 | Human | 253152 | Details Get a Quote |
| EPHX4 Knockout HeLa Cell Line | EDJ-KQ59239 | Human | 253152 | Details Get a Quote |
