EPHX2
epoxide hydrolase 2, the group of Abhydrolase domain containing|HAD Asp-based non-protein phosphatases
Basic information
Region (hg38): 8:27490781-27545564
Links
Phenotypes
GenCC
Source:
- hypercholesterolemia, familial, 1 (No Known Disease Relationship), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHX2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 29 | 36 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 2 | 3 | |||
| non coding | 0 | |||||
| Total | 0 | 0 | 29 | 7 | 4 |
Variants in EPHX2
This is a list of pathogenic ClinVar variants found in the EPHX2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-27491261-C-T | not specified | Uncertain significance (Jun 16, 2024) | ||
| 8-27491270-G-A | not specified | Uncertain significance (Jan 16, 2024) | ||
| 8-27491271-C-A | Benign/Likely benign (Mar 01, 2023) | |||
| 8-27500931-T-C | not specified | Uncertain significance (Aug 14, 2024) | ||
| 8-27500966-G-T | not specified | Uncertain significance (Aug 14, 2023) | ||
| 8-27500973-C-T | not specified | Uncertain significance (Aug 21, 2024) | ||
| 8-27500979-G-A | Benign/Likely benign (Jan 01, 2023) | |||
| 8-27500984-A-T | not specified | Uncertain significance (Nov 10, 2022) | ||
| 8-27500988-A-G | EPHX2-related disorder | Benign (Oct 21, 2019) | ||
| 8-27501000-C-A | not specified | Uncertain significance (Mar 31, 2024) | ||
| 8-27503683-A-G | EPHX2-related disorder | Benign (Oct 28, 2019) | ||
| 8-27503704-T-A | not specified | Uncertain significance (Feb 23, 2023) | ||
| 8-27503728-C-G | not specified | Uncertain significance (May 01, 2022) | ||
| 8-27503752-T-G | not specified | Uncertain significance (Aug 17, 2022) | ||
| 8-27504994-G-A | not specified | Uncertain significance (Aug 20, 2024) | ||
| 8-27505004-A-T | not specified | Uncertain significance (Jun 27, 2022) | ||
| 8-27505051-G-A | not specified | Uncertain significance (Apr 20, 2024) | ||
| 8-27505060-A-G | not specified | Uncertain significance (Dec 04, 2024) | ||
| 8-27505067-C-T | not specified | Uncertain significance (Apr 27, 2024) | ||
| 8-27505109-A-G | not specified | Likely benign (Oct 01, 2024) | ||
| 8-27505133-C-A | not specified | Uncertain significance (Nov 14, 2023) | ||
| 8-27506875-G-A | not specified | Uncertain significance (Aug 06, 2024) | ||
| 8-27506890-A-G | not specified | Likely benign (Feb 01, 2023) | ||
| 8-27506921-T-C | not specified | Uncertain significance (Oct 29, 2024) | ||
| 8-27506924-G-C | Hypercholesterolemia, familial, 1 | Uncertain significance (Jan 31, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EPHX2 | protein_coding | protein_coding | ENST00000521400 | 19 | 54786 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.79e-21 | 0.00293 | 125577 | 0 | 171 | 125748 | 0.000680 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.238 | 306 | 318 | 0.962 | 0.0000170 | 3647 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00204 | 0.00203 |
| Ashkenazi Jewish | 0.00179 | 0.00179 |
| East Asian | 0.000497 | 0.000489 |
| Finnish | 0.000565 | 0.000554 |
| European (Non-Finnish) | 0.000494 | 0.000484 |
| Middle Eastern | 0.000497 | 0.000489 |
| South Asian | 0.000785 | 0.000784 |
| Other | 0.000824 | 0.000815 |
dbNSFP
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}.;
- Pathway
- Peroxisome - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Arachidonate Epoxygenase - Epoxide Hydrolase;Metapathway biotransformation Phase I and II;eicosanoid metabolism;Metabolism of lipids;Arachidonic acid metabolism;Metabolism of proteins;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Metabolism;Biosynthesis of maresins;Biosynthesis of DHA-derived SPMs;Peroxisomal protein import;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;Putative anti-Inflammatory metabolites formation from EPA;Xenobiotics metabolism;Arachidonic acid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.391
Intolerance Scores
- loftool
- 0.949
- rvis_EVS
- 0.69
- rvis_percentile_EVS
- 85.26
Haploinsufficiency Scores
- pHI
- 0.0948
- hipred
- N
- hipred_score
- 0.170
- ghis
- 0.408
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.910
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ephx2
- Phenotype
- homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype;
Zebrafish Information Network
- Gene name
- ephx2
- Affected structure
- parachordal vessel
- Phenotype tag
- abnormal
- Phenotype quality
- agenesis
Gene ontology
- Biological process
- protein targeting to peroxisome;xenobiotic metabolic process;cellular calcium ion homeostasis;inflammatory response;regulation of blood pressure;response to toxic substance;positive regulation of gene expression;dephosphorylation;drug metabolic process;epoxygenase P450 pathway;cholesterol homeostasis;long-chain fatty acid biosynthetic process;stilbene catabolic process;phospholipid dephosphorylation;reactive oxygen species metabolic process;regulation of cholesterol metabolic process;epoxide metabolic process;positive regulation of blood vessel diameter
- Cellular component
- peroxisome;peroxisomal matrix;cytosol;extracellular exosome
- Molecular function
- magnesium ion binding;epoxide hydrolase activity;signaling receptor binding;toxic substance binding;phosphatase activity;10-hydroxy-9-(phosphonooxy)octadecanoate phosphatase activity;lipid phosphatase activity;protein homodimerization activity