EPHX1

protein-coding

epoxide hydrolase 1

Gene summary

Epoxide hydrolase is a critical biotransformation enzyme that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. Epoxide hydrolase functions in both the activation and detoxification of epoxides. Mutations in this gene cause preeclampsia, epoxide hydrolase deficiency or increased epoxide hydrolase activity. Alternatively spliced transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2008]

Previous symbols:

EPHX

MANE transcript

NM_001136018.4

Inheritance

AR, AD

ClinVar variants

P:1U:87B:35

Top phenotype

Hypercholanemia, familial

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr1:225,810,124-225,845,563

External References & Databases

Ensembl (ENSG00000143819)

Transcript & Mutation Effects

hg38 • Region Span ~35.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial hypercholanemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011905

Submitter: Orphanet

hereditary lipodystrophySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020087

Submitter: PanelApp Australia

hereditary nonpolyposis colon cancerLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0018630

Submitter: ClinGen

Clinical Genomic Database (CGD)

Hypercholanemia, familialAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: As in other forms of familial hypercholanemia, individuals may respond to medical treatment (eg, with ursodeoxycholic acid)

Refs: 12878321; 15768832

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EPHX1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 72

EPHX1-related disorderTotal: 41

not providedTotal: 15

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Hereditary lipodystrophyTotal: 1

Decreased total neutrophil countTotal: 1

Hypercholanemia, familial 1Total: 1

Decreased total lymphocyte countTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136018.4. 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 clinvar	13 clinvar	6 clinvar	23
missense		1 clinvar	76 clinvar	10 clinvar	6 clinvar	93
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	87	23	12	123

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 142 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136018.4	RefSeq	NP_001129490.1	8	MANE Select
ENST00000272167.10	Ensembl	ENSP00000272167.5	8	MANE Select
NM_000120.4	RefSeq	NP_000111.1	8	Standard
NM_001291163.2	RefSeq	NP_001278092.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

xenobiotic metabolic process
response to toxic substance
response to organic cyclic compound
aromatic compound catabolic process
epoxide metabolic process

Molecular Function

epoxide hydrolase activity
cis-stilbene-oxide hydrolase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366837
Coding exons: 8
Length: 35467
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0563	256	253	1.01	0.0000153	2987
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.665

Intolerance Scores

LoFtool: 0.843
RVIS EVS: 0.71
RVIS percentile EVS: 85.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.226

Gene Damage Prediction

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