EPHX2

epoxide hydrolase 2, the group of Abhydrolase domain containing|HAD Asp-based non-protein phosphatases

Basic information

Region (hg38): 8:27490780-27545564

Links

ENSG00000120915 ∙ NCBI:2053 ∙ OMIM:132811 ∙ HGNC:3402 ∙ Uniprot:P34913 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypercholesterolemia, familial, 1 (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHX2 gene.

• Inborn genetic diseases (24 variants)
• not provided (4 variants)
• Hypercholesterolemia, familial, 1 (1 variants)

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				2		2
missense			24	2		26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	24	4	0

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
8-27491270-G-A		not specified	Uncertain significance (Jan 16, 2024)
8-27491271-C-A			Benign/Likely benign (Mar 01, 2023)
8-27500966-G-T		not specified	Uncertain significance (Aug 14, 2023)
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)
8-27503683-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)
8-27505004-A-T		not specified	Uncertain significance (Jun 27, 2022)
8-27505133-C-A		not specified	Uncertain significance (Nov 14, 2023)
8-27506890-A-G		not specified	Likely benign (Feb 01, 2023)
8-27506924-G-C		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 31, 2020)
8-27511849-C-T		EPHX2-related disorder	Likely benign (Jan 03, 2020)
8-27511879-G-A		not specified	Uncertain significance (Aug 13, 2021)
8-27515727-C-T		not specified	Uncertain significance (Oct 12, 2021)
8-27515728-G-A		not specified	Uncertain significance (Aug 03, 2022)
8-27515757-C-T		not specified	Uncertain significance (Jan 24, 2024)
8-27515792-T-C		EPHX2-related disorder	Likely benign (Sep 23, 2019)
8-27516347-C-T		not specified	Uncertain significance (Feb 15, 2023)
8-27516348-G-A		Hypercholesterolemia, familial, 1	risk factor (May 27, 2005)
8-27516397-C-T		EPHX2-related disorder	Likely benign (Oct 28, 2019)
8-27518053-G-T		not specified	Uncertain significance (Mar 23, 2022)
8-27520878-C-T			Benign (Aug 16, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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