EPHX2
protein-codingepoxide hydrolase 2, the group of Abhydrolase domain containing|HAD Asp-based non-protein phosphatases
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~54.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007750
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EPHX2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001979.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | 8 | |||
| missense | 104 | 8 | 2 | 114 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 117 | 12 | 2 | 131 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001970.2 | 19 | MANE Select | |
| Ensembl | ENSP00000430269.1 | 19 | MANE Select | |
| RefSeq | NP_001243411.1 | 18 | Standard | |
| RefSeq | NP_001243412.1 | 17 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ephx2 | Danio rerio | Structure: parachordal vessel Quality: agenesis abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Peroxisome - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- Etodolac Action Pathway
- Ketoprofen Action Pathway
- Ibuprofen Action Pathway
Biological Process
- protein targeting to peroxisome
- xenobiotic metabolic process
- cellular calcium ion homeostasis
- inflammatory response
- regulation of blood pressure
Molecular Function
- magnesium ion binding
- epoxide hydrolase activity
- signaling receptor binding
- toxic substance binding
- phosphatase activity
Cellular Component
- peroxisome
- peroxisomal matrix
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000521400
- Coding exons
- 19
- Length
- 54786
- Individuals with no LoFs
- 125577
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 171
- Defined
- 125748
- p
- 0.000680
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.238 | 306 | 318 | 0.962 | 0.0000170 | 3647 |
| Missense (PolyPhen) | 56 | 72.914 | 0.76803 | 821 | ||
| Synonymous | -0.193 | 123 | 120 | 1.02 | 0.00000704 | 1032 |
| Loss of Function | 0.302 | 33 | 34.9 | 0.945 | 0.00000157 | 403 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.00093 | 0.00087 | rare |
| Ashkenazi Jewish | 0.0018 | 0.0018 | notable |
| East Asian | 0.00050 | 0.00049 | rare |
| Finnish | 0.00057 | 0.00055 | rare |
| European (Non-Finnish) | 0.00049 | 0.00048 | rare |
| South Asian | 0.00079 | 0.00078 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Bifunctional enzyme (PubMed:12574510). The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:12869654, PubMed:12574510, PubMed:22798687). Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators (PubMed:12869654, PubMed:12574510, PubMed:22798687). The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy- octadec-9E-enoic acid (PubMed:12574510). {ECO:0000250|UniProtKB:P80299, ECO:0000269|PubMed:12574508, ECO:0000269|PubMed:12574510, ECO:0000269|PubMed:12869654, ECO:0000269|PubMed:22798687}.;
Recessive Scores
- pRec
- 0.391
Intolerance Scores
- LoFtool
- 0.949
- RVIS EVS
- 0.69
- RVIS percentile EVS
- 85.26
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.910
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |