EPHX1

epoxide hydrolase 1

Basic information

Region (hg38): 1:225810124-225845563

Previous symbols: [ "EPHX" ]

Links

ENSG00000143819 ∙ NCBI:2052 ∙ OMIM:132810 ∙ HGNC:3401 ∙ Uniprot:P07099 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial hypercholanemia (Supportive), mode of inheritance: AR
• hereditary nonpolyposis colon cancer (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypercholanemia, familial	AR	Gastrointestinal	As in other forms of familial hypercholanemia, individuals may respond to medical treatment (eg, with ursodeoxycholic acid)	Gastrointestinal	12878321; 15768832

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHX1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHX1 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				3	12	15
missense			23	2	5	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					27	27
Total	0	0	23	5	44

Variants in EPHX1

This is a list of pathogenic ClinVar variants found in the EPHX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-225828680-G-A			Benign (Nov 11, 2018)
1-225828696-G-A			Benign (Nov 11, 2018)
1-225828763-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-225828790-C-T		not specified	Uncertain significance (Sep 26, 2022)
1-225828866-A-G		not specified	Uncertain significance (Sep 12, 2023)
1-225828874-C-T			Benign (Jul 06, 2018)
1-225828932-G-A			Benign (Nov 10, 2018)
1-225831546-CA-C			Benign (Jun 19, 2021)
1-225831546-CAAAAAA-C			Benign (Jun 19, 2021)
1-225831546-C-CA			Benign (Jun 20, 2021)
1-225831554-AAAAAAG-A			Benign (Jun 18, 2021)
1-225831555-AAAAAG-A			Benign (Jun 18, 2021)
1-225831560-GAA-G			Benign (Jun 19, 2021)
1-225831560-GAAAA-G			Benign (Jun 21, 2021)
1-225831670-G-T			Benign (Nov 12, 2018)
1-225831799-T-C		EPHX1-related disorder	Benign (Jul 16, 2019)
1-225831807-G-A			Benign (Jul 10, 2018)
1-225831827-G-A		not specified	Uncertain significance (Aug 08, 2022)
1-225831841-C-G		not specified	Uncertain significance (Apr 04, 2024)
1-225831898-T-C			Likely benign (Jun 18, 2018)
1-225831932-T-C		EPOXIDE HYDROLASE 1 POLYMORPHISM • Cystic fibrosis	Benign (Nov 10, 2018)
1-225831952-G-A			Benign (Nov 11, 2018)
1-225832073-G-C			Benign (Nov 11, 2018)
1-225838540-C-G			Benign (Nov 11, 2018)
1-225838651-C-A			Benign (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPHX1	protein_coding	protein_coding	ENST00000366837	8	35467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.22e-9	0.520	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0563	256	253	1.01	0.0000153	2987
Missense in Polyphen		75	88.261	0.84975		1053
Synonymous	-0.597	115	107	1.07	0.00000707	868
Loss of Function	1.11	16	21.6	0.742	0.00000113	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000560	0.000560
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000246	0.000246
Middle Eastern	0.000272	0.000272
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water (By similarity). May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids (PubMed:22798687). {ECO:0000250|UniProtKB:P07687, ECO:0000269|PubMed:22798687}.
• Disease: DISEASE: Familial hypercholanemia (FHCA) [MIM:607748]: A disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. {ECO:0000269|PubMed:12878321}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Bile secretion - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Warfarin Pathway, Pharmacodynamics;Phenytoin Pathway, Pharmacokinetics;Phenytoin (Antiarrhythmic) Action Pathway;Carbamazepine Metabolism Pathway;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Benzene metabolism;Benzo(a)pyrene metabolism;Aflatoxin B1 metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;eicosanoid metabolism;Biological oxidations;Metabolism;Linoleate metabolism;Putative anti-Inflammatory metabolites formation from EPA;Xenobiotics metabolism;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.665

Intolerance Scores

• loftool: 0.843
• rvis_EVS: 0.71
• rvis_percentile_EVS: 85.76

Haploinsufficiency Scores

• pHI: 0.135
• hipred: N
• hipred_score: 0.216
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.226

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Ephx1
• Phenotype: neoplasm; homeostasis/metabolism phenotype

Gene ontology

• Biological process: xenobiotic metabolic process;response to toxic substance;response to organic cyclic compound;aromatic compound catabolic process;epoxide metabolic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;organelle membrane
• Molecular function: epoxide hydrolase activity;cis-stilbene-oxide hydrolase activity