EPHX3

Summary

EPHX3 (epoxide hydrolase 3, HGNC:23760) is a protein-coding gene on chromosome 19p13.12, encoding Epoxide hydrolase 3 (Q9H6B9). Catalyzes the hydrolysis of epoxide-containing fatty acids.

Enables epoxide hydrolase activity. Involved in epoxide metabolic process. Located in intracellular membrane-bounded organelle and membrane.

Source: NCBI Gene 79852 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_024794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23760
Approved symbol	EPHX3
Name	epoxide hydrolase 3
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22408
Ensembl gene	ENSG00000105131
Ensembl biotype	protein_coding
OMIM	617400
Entrez	79852

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000221730, ENST00000435261, ENST00000594042, ENST00000602233, ENST00000851186, ENST00000851188, ENST00000915320, ENST00000915321, ENST00000915322, ENST00000915323, ENST00000915324, ENST00000915325, ENST00000915326, ENST00000915327, ENST00000915328, ENST00000915329, ENST00000915330

RefSeq mRNA: 2 — MANE Select: NM_024794 NM_001142886, NM_024794

CCDS: CCDS12327

Canonical transcript exons

ENST00000221730 — 7 exons

Exon	Start	End
ENSE00000689080	15231776	15231861
ENSE00000689081	15231239	15231396
ENSE00000689082	15230962	15231090
ENSE00000689083	15227997	15228100
ENSE00000689084	15227771	15227907
ENSE00000873270	15231969	15232448
ENSE00001695678	15226919	15227662

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 96.23.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2341 / max 51.2899, expressed in 246 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179712	0.7379	149
179714	0.2814	128
179713	0.1849	86
179711	0.0299	9

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.23	gold quality
cervix squamous epithelium	UBERON:0006922	93.66	silver quality
skin of abdomen	UBERON:0001416	93.65	gold quality
skin of leg	UBERON:0001511	93.45	gold quality
esophagus mucosa	UBERON:0002469	93.15	gold quality
penis	UBERON:0000989	92.34	gold quality
zone of skin	UBERON:0000014	92.13	gold quality
upper leg skin	UBERON:0004262	91.58	gold quality
mammalian vulva	UBERON:0000997	90.97	gold quality
upper arm skin	UBERON:0004263	90.67	gold quality
epithelium of esophagus	UBERON:0001976	88.02	gold quality
squamous epithelium	UBERON:0006914	87.90	gold quality
gingiva	UBERON:0001828	87.72	gold quality
esophagus squamous epithelium	UBERON:0006920	87.39	gold quality
cervix epithelium	UBERON:0004801	87.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.79	gold quality
gingival epithelium	UBERON:0001949	85.99	gold quality
oral cavity	UBERON:0000167	85.82	gold quality
pharyngeal mucosa	UBERON:0000355	84.43	gold quality
vagina	UBERON:0000996	83.06	gold quality
buccal mucosa cell	CL:0002336	82.97	silver quality
amniotic fluid	UBERON:0000173	82.78	gold quality
skin of hip	UBERON:0001554	81.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.54	gold quality
tongue squamous epithelium	UBERON:0006919	81.46	silver quality
nipple	UBERON:0002030	81.34	gold quality
palpebral conjunctiva	UBERON:0001812	79.34	gold quality
esophagus	UBERON:0001043	72.20	gold quality
uterine cervix	UBERON:0000002	71.37	gold quality
body of tongue	UBERON:0011876	70.84	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting EPHX3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-6872-3P	97.08	66.99	750
HSA-MIR-6823-5P	96.26	65.69	919
HSA-MIR-5708	90.54	64.01	66

Literature-anchored findings (GeneRIF, showing 4)

• methylation of the ABHD9 is significantly associated with prostate cancer prognosis. (PMID:17437806)
• The identification of two human epoxide hydrolases: EH3 and EH4. (PMID:22798687)
• These results validate the association between promoter hypermethylation of ABHD9 and HOXD3 and prostate cancer recurrence (PMID:24718283)
• Relative Importance of Soluble and Microsomal Epoxide Hydrolases for the Hydrolysis of Epoxy-Fatty Acids in Human Tissues. (PMID:34066758)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-122a22.2	ENSDARG00000095821
mus_musculus	Ephx3	ENSMUSG00000037577
rattus_norvegicus	Ephx3	ENSRNOG00000027319
drosophila_melanogaster	CG5704	FBGN0026570
drosophila_melanogaster	CG5707	FBGN0026593
drosophila_melanogaster	CG15879	FBGN0035309
drosophila_melanogaster	CG15820	FBGN0035312
drosophila_melanogaster	CG11309	FBGN0037070
drosophila_melanogaster	CG7632	FBGN0037071
caenorhabditis_elegans	C31H5.1	WBGENE00007854
caenorhabditis_elegans		WBGENE00010628
caenorhabditis_elegans		WBGENE00017335
caenorhabditis_elegans		WBGENE00018077
caenorhabditis_elegans		WBGENE00019525
caenorhabditis_elegans		WBGENE00022258
caenorhabditis_elegans		WBGENE00022259
caenorhabditis_elegans		WBGENE00022260

Paralogs (12): ABHD5 (ENSG00000011198), ABHD4 (ENSG00000100439), ABHD11 (ENSG00000106077), MEST (ENSG00000106484), ABHD14B (ENSG00000114779), EPHX2 (ENSG00000120915), ABHD8 (ENSG00000127220), BPHL (ENSG00000137274), ABHD6 (ENSG00000163686), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

Epoxide hydrolase 3 — Q9H6B9 (reviewed: Q9H6B9)

Alternative names: Abhydrolase domain-containing protein 9

All UniProt accessions (2): Q9H6B9, M0QX48

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of epoxide-containing fatty acids. Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.

Subcellular location. Microsome membrane.

Activity regulation. Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA).

Similarity. Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.

RefSeq proteins (2): NP_001136358, NP_079070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR000639	Epox_hydrolase-like	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF00561

Enzyme classification (BRENDA):

• EC 3.3.2.10 — soluble epoxide hydrolase (BRENDA: 48 organisms, 343 substrates, 1613 inhibitors, 109 Km, 60 kcat entries)

Substrate kinetics (BRENDA)

40 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TRANS-STILBENE OXIDE	0.0017–0.011	12
14,15-EPOXYEICOSATRIENOIC ACID	0.007–0.076	7
TRANS-1,3-DIPHENYLPROPENE OXIDE	0.0033–0.0253	6
(R)-STYRENE OXIDE	0.001–21.8	5
(S)-STYRENE OXIDE	0.07–8.33	5
1-MYRISTOYL-SN-GLYCEROL 3-PHOSPHATE	0.006–0.019	5
2,3-EPOXY-1,3-DIPHENYL-PROPANE	0.0043–0.0083	5
ATTOPHOS	0.0074–0.017	5
EPOXY FLUOR 7	0.0058–0.0151	5
CIS-STILBENE OXIDE	0.027–0.076	4
STYRENE OXIDE	1.36–3.4	3
TRANS-DIPHENYLPROPENE OXIDE	0.0078–0.01	3
(10R)-HYDROXY-(11S,12S)-EPOXY-(5Z,8Z,14Z)-EICOSA	0.0108–0.0147	2
(8R)-HYDROXY-(11S,12S)-EPOXY-(5Z,9E,14Z)-EICOSAT	0.0046–0.0073	2
(R)-P-NITROSTYRENE OXIDE	0.009–0.6	2

Catalyzed reactions (Rhea), 6 shown:

• an epoxide + H2O = an ethanediol (RHEA:19037)
• 9,10-epoxy-(12Z)-octadecenoate + H2O = 9,10-dihydroxy-(12Z)-octadecenoate (RHEA:44032)
• 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H2O = 14,15-dihydroxy-(5Z,8Z,11Z)-eicosatrienoate (RHEA:44040)
• 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H2O = 11,12-dihydroxy-(5Z,8Z,14Z)-eicosatrienoate (RHEA:44044)
• 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H2O = 8,9-dihydroxy-(5Z,11Z,14Z)-eicosatrienoate (RHEA:44048)
• 9,10-epoxyoctadecanoate + H2O = 9,10-dihydroxyoctadecanoate (RHEA:45352)

UniProt features (12 total): mutagenesis site 7, active site 3, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6B9-F1	94.38	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 173 (nucleophile); 281 (proton donor); 337 (proton acceptor)

Mutagenesis-validated functional residues (7):

Position	Phenotype
307	loss of catalytic activity.
337	loss of catalytic activity.
173	loss of catalytic activity.
173	no effect on catalytic activity.
220	loss of catalytic activity.
280	no effect on catalytic activity.
281	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, JAEGER_METASTASIS_DN, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_LIPID_METABOLIC_PROCESS, chr19p13, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ETHER_BONDS, RICKMAN_HEAD_AND_NECK_CANCER_E, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, ANDERSEN_CHOLANGIOCARCINOMA_CLASS2, GOMF_EPOXIDE_HYDROLASE_ACTIVITY, SMID_BREAST_CANCER_RELAPSE_IN_BONE_DN, KRAS.600.LUNG.BREAST_UP.V1_DN, SETD7_TARGET_GENES, MIR10395_3P

GO Biological Process (2): lipid metabolic process (GO:0006629), epoxide metabolic process (GO:0097176)

GO Molecular Function (3): epoxide hydrolase activity (GO:0004301), hydrolase activity (GO:0016787), catalytic activity (GO:0003824)

GO Cellular Component (3): membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
metabolic process	1
ether hydrolase activity	1
catalytic activity	1
molecular_function	1
cellular anatomical structure	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHX3	EPHX1	P07099	666
EPHX3	HACL2	A1L0T0	527
EPHX3	TRIR	Q9BQ61	510
EPHX3	NPBWR1	P48145	504
EPHX3	H4C7	Q99525	481
EPHX3	H4C16	P02304	480
EPHX3	HSP90AB1	P08238	449
EPHX3	GOLGA8S	H3BPF8	447
EPHX3	ABHD16B	Q9H3Z7	411
EPHX3	SYDE1	Q6ZW31	410
EPHX3	SUCO	Q9UBS9	410
EPHX3	ABHD15	Q6UXT9	403
EPHX3	ZNF134	P52741	391
EPHX3	ABHD13	Q7L211	382
EPHX3	TSPYL4	Q9UJ04	380

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): EPHX3 (Affinity Capture-MS)

ESM2 similar proteins: A0A193KX02, A0A5F8AH41, A1Y9I9, A4FUH1, A6NM43, A7YY46, B6CZ46, B6CZ56, B6CZ62, D3ZBP4, D3ZX08, E9QAM5, H9TB19, O43542, P10937, P11086, P40935, P41226, P55205, P86243, Q14CH7, Q2M296, Q32Q92, Q3URQ7, Q3V1F8, Q3ZBE0, Q53S58, Q5E9L5, Q5JTZ9, Q5JU69, Q5M936, Q5SS80, Q5XIL6, Q69ZP3, Q6AYR4, Q6NZB1, Q6ZSI9, Q80YU0, Q8N490, Q8R1J9

Diamond homologs: A0A126P745, A0A1L5BTC1, A0A242M8J4, A7MFY0, A8IAD8, B0SY51, B2HJU9, B4RF90, B8H3S9, C5CN82, D4Z2G1, G5EDL5, I6YC03, I6YGS0, O31158, O52866, P0A3G2, P0A3G3, P0A3G4, P0A573, P0DO68, P0DO69, P0DO70, P19076, P22643, P22862, P23106, P23133, P25026, P34913, P34914, P46542, P46544, P49323, P59336, P64302, P64304, P80299, P95276, P9WMS0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1023 predictions. Top by Δscore:

Variant	Effect	Δscore
19:15227908:C:CC	acceptor_gain	1.0000
19:15227992:TGTA:T	donor_loss	1.0000
19:15227993:GTACC:G	donor_loss	1.0000
19:15227996:C:A	donor_loss	1.0000
19:15228055:A:C	acceptor_gain	1.0000
19:15228097:TAGT:T	acceptor_gain	1.0000
19:15228099:GT:G	acceptor_gain	1.0000
19:15228099:GTC:G	acceptor_loss	1.0000
19:15228100:TC:T	acceptor_loss	1.0000
19:15228101:C:CC	acceptor_gain	1.0000
19:15228101:CT:C	acceptor_loss	1.0000
19:15228102:T:G	acceptor_loss	1.0000
19:15231241:AGG:A	donor_gain	1.0000
19:15231256:T:TA	donor_gain	1.0000
19:15231401:C:CT	acceptor_gain	1.0000
19:15231402:A:T	acceptor_gain	1.0000
19:15227663:C:CG	acceptor_loss	0.9900
19:15227670:C:CT	acceptor_gain	0.9900
19:15227765:TCTCA:T	donor_loss	0.9900
19:15227766:CTCA:C	donor_loss	0.9900
19:15227767:TCAC:T	donor_loss	0.9900
19:15227770:C:CG	donor_loss	0.9900
19:15227907:TCT:T	acceptor_loss	0.9900
19:15228096:ATAGT:A	acceptor_gain	0.9900
19:15228098:AGT:A	acceptor_gain	0.9900
19:15228106:G:C	acceptor_gain	0.9900
19:15228106:G:GC	acceptor_gain	0.9900
19:15231254:CAT:C	donor_gain	0.9900
19:15231256:T:C	donor_gain	0.9900
19:15231301:T:TA	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000363868 (19:15238736 G>A,C), RS1000431304 (19:15233421 G>A,C), RS1000499144 (19:15230816 G>A), RS1000812217 (19:15236550 G>A,C,T), RS1000843564 (19:15236720 G>C), RS1001153722 (19:15238514 C>A,T), RS1001268775 (19:15232931 G>A,T), RS1001421351 (19:15226500 G>A), RS1001641633 (19:15232524 G>A), RS1002216536 (19:15233996 G>A,C), RS1002650754 (19:15231681 C>G,T), RS1002673781 (19:15234355 T>G), RS1002814281 (19:15237500 G>A), RS1002971021 (19:15231689 A>T), RS1003329202 (19:15231374 G>A)

Disease associations

OMIM: gene MIM:617400 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004602_265	Mean corpuscular volume	5.000000e-10
GCST90002390_531	Mean corpuscular hemoglobin	6.000000e-19
GCST90002392_70	Mean corpuscular volume	5.000000e-22
GCST90002397_191	Mean spheric corpuscular volume	4.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	8
entinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
fluorene-9-bisphenol	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
mono-(2-ethylhexyl)phthalate	increases abundance, decreases methylation	1
avobenzone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
Decitabine	increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	increases abundance, decreases methylation	1
Lead	affects methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.