CYP2E1

Summary

CYP2E1 (cytochrome P450 family 2 subfamily E member 1, HGNC:2631) is a protein-coding gene on chromosome 10q26.3, encoding Cytochrome P450 2E1 (P05181). A cytochrome P450 monooxygenase involved in the metabolism of fatty acids.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer.

Source: NCBI Gene 1571 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 143 total — 1 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000773

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2631
Approved symbol	CYP2E1
Name	cytochrome P450 family 2 subfamily E member 1
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000130649
Ensembl biotype	protein_coding
OMIM	124040
Entrez	1571

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 14 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000252945, ENST00000368520, ENST00000418356, ENST00000421586, ENST00000463117, ENST00000469258, ENST00000477500, ENST00000480558, ENST00000541080, ENST00000541261, ENST00000883802, ENST00000883803, ENST00000883804, ENST00000883805, ENST00000883806, ENST00000883807, ENST00000883808, ENST00000883809, ENST00000883810

RefSeq mRNA: 1 — MANE Select: NM_000773 NM_000773

CCDS: CCDS7686

Canonical transcript exons

ENST00000252945 — 9 exons

Exon	Start	End
ENSE00000896717	133527363	133527572
ENSE00002236194	133538780	133539123
ENSE00003470843	133532692	133532868
ENSE00003495287	133528481	133528640
ENSE00003518669	133537063	133537250
ENSE00003566623	133537751	133537892
ENSE00003610978	133533756	133533897
ENSE00003657609	133531585	133531734
ENSE00003888883	133532124	133532284

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 99.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 30.3660 / max 11983.2253, expressed in 97 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107807	29.1900	35
107827	0.3474	7
107812	0.1783	6
107809	0.1214	38
107814	0.0959	7
107828	0.0898	11
107813	0.0722	6
107808	0.0676	31
107826	0.0476	7
107831	0.0442	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.93	gold quality
liver	UBERON:0002107	98.43	gold quality
lower esophagus mucosa	UBERON:0035834	92.02	gold quality
esophagus squamous epithelium	UBERON:0006920	90.53	gold quality
epithelium of esophagus	UBERON:0001976	89.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.50	gold quality
cerebellar hemisphere	UBERON:0002245	88.24	gold quality
cerebellar cortex	UBERON:0002129	88.03	gold quality
body of pancreas	UBERON:0001150	86.20	gold quality
esophagus mucosa	UBERON:0002469	86.18	gold quality
cerebellum	UBERON:0002037	85.77	gold quality
cortical plate	UBERON:0005343	85.70	gold quality
right frontal lobe	UBERON:0002810	84.82	gold quality
right uterine tube	UBERON:0001302	84.40	gold quality
skin of leg	UBERON:0001511	83.82	gold quality
skin of abdomen	UBERON:0001416	82.80	gold quality
endothelial cell	CL:0000115	82.43	gold quality
middle temporal gyrus	UBERON:0002771	82.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.38	gold quality
prefrontal cortex	UBERON:0000451	82.19	gold quality
upper leg skin	UBERON:0004262	82.01	gold quality
oral cavity	UBERON:0000167	81.55	gold quality
zone of skin	UBERON:0000014	81.24	gold quality
esophagus	UBERON:0001043	81.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.93	gold quality
tonsil	UBERON:0002372	80.55	gold quality
primary visual cortex	UBERON:0002436	80.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.35	gold quality
body of stomach	UBERON:0001161	80.28	gold quality
buccal mucosa cell	CL:0002336	80.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	12013.10
E-HCAD-9	yes	3735.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, CEBPB, CREB1, DBP, HNF1A, HNF1B, NFAT5, NFATC1, NFE2L2, NFKB1, NR2F1, RELA, REST, SP1, STAT6

miRNA regulators (miRDB)

9 targeting CYP2E1, 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-607	99.97	73.62	5593
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-96-3P	97.47	68.03	839

Literature-anchored findings (GeneRIF, showing 40)

• There is a correlation between the RsaI polymorphism homozygous uncut genotype in the CYP2E1 gene and a higher relative risk of nasopharyngeal carcinoma development in the Thai or Chinese populations in Thailand. (PMID:11389775)
• increased translation of collagen mRNA by CYP2E1-derived reactive oxygen species is responsible for the increase in collagen protein (PMID:11782477)
• Damage to mitochondria may be a critical step for cellular toxicity by CYP2E1-derived reactive oxygen species (PMID:11907164)
• CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism (PMID:11960914)
• Individuals possessing more susceptible CYP2E1 c2c2 genotypes were more likely to reveal p53 overexpression. Susceptible CYP2E1 genotypes may modulate the mutation of the p53 gene among VCM-exposed workers. (PMID:12010862)
• In the CYP2E1 gene 5’-flanking region polymorphism, patients with esophageal cancer showed significantly higher frequency of the A4/A4 genotype compared with the control subjects (p = 0.02), but no difference was found in patients with lung cancer. (PMID:12198369)
• expression of human cytochrome P450 2E1 gene in embryonic nasopharynx, nasopharyngeal cancer cell lines and tissue (PMID:12452057)
• Overexpression of this enzyme overexpression up-regulates both non-specific delta-aminolevulinate synthase and heme oxygenase-1 in a human hepatoma cell line. (PMID:12469218)
• substitution of residue 363 in cyp2e1 resulted in significant alterations of the metabolite profile for the side chain hydroxylation of 7-butoxycoumarin (PMID:12490624)
• The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. (PMID:12552594)
• Polymorphisms of alcohol-metabolizing enzymes: analyses of mutations on the CYP2E1, ADH2, ADH3 and ALDH2 genes in a Mexican-American population living in the Los Angeles area. (PMID:12554615)
• CYP2E1 genetic polymorphism may be associated with susceptibility to breast cancer in alcohol-consuming women. (PMID:12563175)
• hepatic cytochrome P450 2E1 activity and lymphocyte cytochrome P450 2E1 expression are enhanced in nondiabetic nonalcoholic steatohepatitis (PMID:12601351)
• CYP 2E1 genetic polymorphism may be associated with susceptibility to antituberculosis drug-induced hepatitis. (PMID:12668988)
• This study shown that the genotypes of CYP2E1 are associated with clinical features of alcoholics. (PMID:12707490)
• Down-regulation of cytochrome P450 CYP2E1 is associated with breast cancer (PMID:12738724)
• Proteasome activity plays an important role in modulating CYP2E1-mediated toxicity in HepG2 cells by regulating CYP2E1 levels and by removal of oxidized proteins. (PMID:12774019)
• HO-1 induction was observed in the livers of chronic alcohol-fed mice or pyrazole-treated rats, conditions known to elevate CYP2E1 levels. (PMID:12777398)
• P450 2E1 has a role in inducing heme oxygenase-1 through ERK MAPK pathway (PMID:12777398)
• association of CYP2E1*1D with alcohol and nicotine dependence suggests that CYP2E1 may contribute to the development of these dependencies (PMID:12777962)
• CYP2E1 and NQO1 genotypes may play an important role in development of smoking related bladder cancer among Korean men (PMID:12777965)
• CYP2E1 has a role in oxidative stress causing mitochondrial damage along with phospholipase A2 (PMID:12813050)
• Arg76 is closely associated with the function of CYP2E1, and that the genetic polymorphism of cytochrome p450 2E1 is one cause of interindividual differences in the toxicity of xenobiotics (PMID:12851035)
• These results show that CYP2E1 protein is expressed in both tumour and normal breast tissue with an increased expression in breast tumours. (PMID:12860273)
• hepatic CYP2E1 activity is up-regulated in morbidly obese subjects (PMID:12883487)
• Transcriptional activity of the mutant allele of the tandem repeat polymorphism in the 5’-flanking region of the CYP2E1 gene is greater than that of the wild type. (PMID:12960506)
• CYP2E1 was clearly expressed in human fetal liver. (PMID:14500779)
• Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions, and after acute and chronic alcohol treatment. (PMID:14527082)
• biochemical and toxicological properties of CYP2E1(review) (PMID:14527082)
• The genetic polymorphism of CYPIIE1 on the position of Pst I and Rsa I is related to the susceptibility of fatty liver. (PMID:14606109)
• The cDNA of human CYP2E1 can be successfully cloned, and a cell line, HepG2-CYP2E1 can efficiently express mRNA and has CYP2E1 activity. (PMID:14669323)
• enhanced injury in hepatocytes over expressing both Hepatitis C virus core protein and CYP2E1 is mediated by increases in oxidative stress. (PMID:14695664)
• CYP2E1 polymorphisms are associated with incomplete intestinal metaplasia in a high-risk area of stomach cancer (PMID:14696128)
• The objective of this study was to analyze the effect of the green tea flavanol epigallocatechin-3-gallate (EGCG), which has been shown to prevent alcohol-induced liver damage, on CYP2E1-mediated toxicity in HepG2 cells overexpressing CYP2E1 (E47 cells). (PMID:15036355)
• CYP2E1 is a unique gene expressing in liver but did not express in hepatocellular carcinoma (PMID:15162526)
• polymorphism and susceptibility to cirrhosis or pancreatitis in alcoholics (PMID:15215328)
• marked impairment of CYP enzyme activity during allograft rejection which is presumably secondary to an increased intragraft production of proinflammatory cytokines and NO. (PMID:15349722)
• overexpression of human CYP2E1 activates acetaminophen to reactive metabolites which damage mitochondria, form protein adducts, and result in toxicity to HepG2 cells (PMID:15532721)
• increased hepatocyte CYP2E1 expression and the presence of steatohepatitis result in the down-regulation of insulin signaling (PMID:15632182)
• The aim of this study was to determine whether hepatitis C virus core protein and alcohol-inducible cytochrome P450 2E1 contribute to reactive oxygen species production and cytotoxicity in human hepatoma cells. (PMID:15633127)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp2e1	ENSMUSG00000025479
rattus_norvegicus	Cyp2e1	ENSRNOG00000012458

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2E1 — P05181 (reviewed: P05181)

Alternative names: 4-nitrophenol 2-hydroxylase, CYPIIE1, Cytochrome P450-J

All UniProt accessions (5): P05181, F5H694, H0Y593, H0Y7H4, H0YGV5

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH–hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids. May be involved in the oxidative metabolism of xenobiotics.

Subunit / interactions. Interacts with chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane. Mitochondrion inner membrane.

Activity regulation. The omega-1 hydroxylase activity is stimulated by cytochrome b5.

Induction. By ethanol and isoniazid.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008070	Cyt_P450_E_grp-I_CYP2E-like	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Catalyzed reactions (Rhea), 7 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)
• 4-nitrophenol + NADPH + O2 + H(+) = 4-nitrocatechol + NADP(+) + H2O (RHEA:26205)
• dodecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 11-hydroxydodecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39751)
• (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:39787)
• (5Z,8Z,11Z)-eicosatrienoate + reduced [NADPH–hemoprotein reductase] + O2 = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:50076)
• (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH–hemoprotein reductase] + O2 = 21-hydroxy-(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:50088)
• tetradecanoate + reduced [NADPH–hemoprotein reductase] + O2 = 13-hydroxytetradecanoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:50096)

UniProt features (58 total): helix 22, strand 15, sequence conflict 6, turn 6, sequence variant 6, binding site 2, chain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
3E6I	X-RAY DIFFRACTION	2.2
3T3Z	X-RAY DIFFRACTION	2.35
3E4E	X-RAY DIFFRACTION	2.6
3GPH	X-RAY DIFFRACTION	2.7
3KOH	X-RAY DIFFRACTION	2.9
3LC4	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05181-F1	96.22	0.92

Functional residue map

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

Ligand- & substrate-binding residues (2): 298–303; 437 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions
R-HSA-9027307	Biosynthesis of maresin-like SPMs
R-HSA-9749641	Aspirin ADME
R-HSA-9753281	Paracetamol ADME

MSigDB gene sets: 268 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_LIPID_MODIFICATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, MORF_FLT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_MSH3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GNF2_GSTM1, GNF2_HPN, MORF_BRCA1, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, HNF1_Q6

GO Biological Process (14): long-chain fatty acid metabolic process (GO:0001676), lipid hydroxylation (GO:0002933), xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), response to bacterium (GO:0009617), monoterpenoid metabolic process (GO:0016098), carbon tetrachloride metabolic process (GO:0018885), benzene metabolic process (GO:0018910), 4-nitrophenol metabolic process (GO:0018960), epoxygenase P450 pathway (GO:0019373), halogenated hydrocarbon metabolic process (GO:0042197), long-chain fatty acid biosynthetic process (GO:0042759), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (15): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), arachidonate epoxygenase activity (GO:0008392), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen (GO:0016709), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), 4-nitrophenol 2-monooxygenase activity (GO:0018601), oxygen binding (GO:0019825), enzyme binding (GO:0019899), heme binding (GO:0020037), Hsp70 protein binding (GO:0030544), Hsp90 protein binding (GO:0051879), long-chain fatty acid omega-1 hydroxylase activity (GO:0120319), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), mitochondrial inner membrane (GO:0005743), endoplasmic reticulum membrane (GO:0005789), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Drug ADME	2
Cytochrome P450 - arranged by substrate type	1
Xenobiotics	1
Biosynthesis of maresins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
oxidoreductase activity	2
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
heat shock protein binding	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
fatty acid metabolic process	1
lipid modification	1
metabolic process	1
cellular response to xenobiotic stimulus	1
response to other organism	1
terpenoid metabolic process	1
halogenated hydrocarbon metabolic process	1
benzene-containing compound metabolic process	1
hydrocarbon metabolic process	1
phenol-containing compound metabolic process	1
arachidonate metabolic process	1
xenobiotic metabolic process	1
organohalogen metabolic process	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
primary metabolic process	1
monocarboxylic acid metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	1
small molecule binding	1
protein binding	1
tetrapyrrole binding	1
protein-folding chaperone binding	1
fatty acid omega-1 hydroxylase activity	1
cation binding	1
intracellular anatomical structure	1
organelle inner membrane	1
mitochondrial membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

2666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2E1	FANCG	O15287	952
CYP2E1	CYB5A	P00167	941
CYP2E1	PPIG	Q13427	939
CYP2E1	CYB5B	O43169	894
CYP2E1	B3GAT2	Q9NPZ5	886
CYP2E1	ADH1B	P00325	877
CYP2E1	CYP3A4	P05184	863
CYP2E1	ALDH2	P05091	837
CYP2E1	POR	P16435	827
CYP2E1	UGT1A6	P19224	797
CYP2E1	GSTP1	P09211	784
CYP2E1	GSTM1	P09488	771
CYP2E1	AVP	P01185	770
CYP2E1	CYP1A2	P05177	748
CYP2E1	CYP3A5	P20815	739

IntAct

13 interactions, top by confidence:

A	B	Type	Score
CYP2E1	RMDN1	psi-mi:“MI:0914”(association)	0.530
CYP2E1	CLU	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	ECHS1	psi-mi:“MI:0915”(physical association)	0.370
GATM	CYP2E1	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	MAFG	psi-mi:“MI:0915”(physical association)	0.370
PTN	CYP2E1	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	NMI	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	ABCA5	psi-mi:“MI:0915”(physical association)	0.370
RPL13A	CYP2E1	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	AGXT2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (26): POR (PCA), CYP2E1 (PCA), RMDN1 (Affinity Capture-MS), POLR3E (Affinity Capture-MS), CYP2E1 (Two-hybrid), CYP2E1 (Affinity Capture-RNA), POLR3E (Affinity Capture-MS), CYP2E1 (Reconstituted Complex), RMDN1 (Affinity Capture-MS), CYP2E1 (Biochemical Activity), CYP2E1 (Biochemical Activity), CYP2E1 (Reconstituted Complex), POR (Reconstituted Complex), CYP2E1 (Reconstituted Complex), CYP2E1 (Two-hybrid)

ESM2 similar proteins: E9Q5K4, O55071, O62671, P00179, P00180, P00181, P00182, P05178, P05179, P05180, P05181, P08683, P11371, P11509, P11711, P11712, P12790, P13107, P15123, P15392, P17666, P19225, P20678, P20812, P20814, P20852, P20853, P24454, P24470, P33260, P33261, P33263, P33264, P33265, P33272, P33273, P56593, P56594, P56654, P56655

Diamond homologs: A0A067GFT7, A0A068AA98, A0A084API1, A0A0C3HJL3, A0A0F7U0K0, A0A0P0ZEA9, A0A1B4XBH0, A0A1L7VEQ6, A0A1L9WQK2, A0A1R3RGJ7, A0A1V1FNM9, A0A218NGS0, A0A2P1DPA5, A0A386KZI3, A0A3S9NM20, A0A411KUQ5, A0A455ZIK8, A0A455ZM03, A0A481WPJ6, A0A517FNB9, A0A5B8NBK9, A0A5B8ND26, A0A6S6QPY4, A0A831A9C9, A0A8K1AW54, A1C8C2, A2R6G9, A6YIH8, B5BSX1, B6HFX9, B8NHD9, C0SJS4, C8V0D4, C8V7P3, C9K1X6, D1MX85, F1SY77, G0KYB2, G1XU01, G3Y420

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HBB	“up-regulates activity”	CYP2E1
HBA1	“up-regulates activity”	CYP2E1

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	56
Likely benign	11
Benign	63

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3024574	GRCh37/hg19 10q26.3(chr10:131299771-135441274)x1	Pathogenic
221737	GRCh38/hg38 10q26.3(chr10:133443259-133566207)x1	Likely pathogenic
549627	NC_000010.10:g.135252327_135378761del126435	Likely pathogenic

SpliceAI

3924 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133527356:GGATT:G	acceptor_gain	1.0000
10:133528638:GGG:G	donor_gain	1.0000
10:133528639:GGG:G	donor_gain	1.0000
10:133531724:G:GT	donor_gain	1.0000
10:133531731:CAAGG:C	donor_loss	1.0000
10:133531732:AAGGT:A	donor_loss	1.0000
10:133531734:GGTG:G	donor_loss	1.0000
10:133531735:G:GA	donor_loss	1.0000
10:133531736:T:A	donor_loss	1.0000
10:133532218:G:GT	donor_gain	1.0000
10:133533745:C:CA	acceptor_gain	1.0000
10:133537062:GAGAA:G	acceptor_gain	1.0000
10:133537234:GA:G	donor_gain	1.0000
10:133537250:GGT:G	donor_gain	1.0000
10:133537252:T:G	donor_gain	1.0000
10:133537852:A:T	donor_gain	1.0000
10:133537855:GTT:G	donor_gain	1.0000
10:133537856:TTT:T	donor_gain	1.0000
10:133537857:T:G	donor_gain	1.0000
10:133555345:GCTTA:G	donor_loss	1.0000
10:133555346:CTTAC:C	donor_loss	1.0000
10:133555347:TTA:T	donor_loss	1.0000
10:133555348:TA:T	donor_loss	1.0000
10:133555350:C:A	donor_loss	1.0000
10:133555434:TCAGC:T	acceptor_gain	1.0000
10:133555435:CAGC:C	acceptor_gain	1.0000
10:133555435:CAGCC:C	acceptor_gain	1.0000
10:133555436:AGC:A	acceptor_gain	1.0000
10:133555437:GC:G	acceptor_gain	1.0000
10:133555438:CC:C	acceptor_gain	1.0000

AlphaMissense

3274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133537883:T:C	F430L	0.998
10:133537885:T:A	F430L	0.998
10:133537885:T:G	F430L	0.998
10:133537171:G:C	R359P	0.995
10:133537835:T:C	F414L	0.995
10:133537837:C:A	F414L	0.995
10:133537837:C:G	F414L	0.995
10:133537149:G:C	A352P	0.994
10:133538780:G:A	G433E	0.994
10:133537162:A:T	E356V	0.993
10:133537802:T:C	F403L	0.993
10:133537804:T:A	F403L	0.993
10:133537804:T:G	F403L	0.993
10:133528603:A:C	R100S	0.992
10:133528603:A:T	R100S	0.992
10:133537203:C:G	H370D	0.992
10:133537836:T:C	F414S	0.991
10:133537883:T:A	F430I	0.991
10:133537884:T:G	F430C	0.991
10:133537821:T:C	F409S	0.990
10:133538780:G:T	G433V	0.990
10:133533828:G:T	G300W	0.989
10:133537820:T:C	F409L	0.989
10:133537822:T:A	F409L	0.989
10:133537822:T:G	F409L	0.989
10:133533861:G:A	G311R	0.988
10:133533861:G:C	G311R	0.988
10:133537150:C:A	A352D	0.988
10:133537884:T:C	F430S	0.988
10:133538798:G:A	G439E	0.988

dbSNP variants (sampled 300 via entrez): RS1000422283 (10:133538612 C>T), RS1000612057 (10:133533386 C>A), RS1001045478 (10:133539372 A>G), RS1001770872 (10:133530019 C>A), RS1002032606 (10:133527647 G>A), RS1002291352 (10:133536808 G>T), RS1002296018 (10:133539094 A>G), RS1002432599 (10:133535899 C>G), RS1002560319 (10:133529335 A>C,G), RS1002618872 (10:133536039 A>G), RS1002748437 (10:133530186 C>A,T), RS1003302581 (10:133526326 G>A), RS1003567474 (10:133528246 C>A), RS1003614796 (10:133528123 T>C), RS1003698204 (10:133531933 G>A,T)

Disease associations

OMIM: gene MIM:124040 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (3): preeclampsia (MONDO:0005081), primary ovarian failure (MONDO:0005387), primary amenorrhea (MONDO:1060208)

Orphanet (2): Preeclampsia (Orphanet:275555), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001356_25	Gout	1.000000e-07
GCST001356_26	Gout	1.000000e-07
GCST001524_23	Visceral adipose tissue/subcutaneous adipose tissue ratio	4.000000e-06
GCST001762_586	Obesity-related traits	3.000000e-06
GCST008526_35	Coffee consumption	1.000000e-07
GCST009530_2	Childhood body mass index	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0006781	coffee consumption measurement
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523986 (PROTEIN FAMILY), CHEMBL5281 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 25,123 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL3287379	CONTEZOLID	3	67
CHEMBL961	DITIOCARB	2	9,516

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

PharmGKB clinical annotations

10 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2E11A, CYP2E15B	Toxicity	3	Drugs For Treatment Of Tuberculosis	Tuberculosis
rs2031920	Toxicity	3	ethanol	Alcohol abuse
rs2031920	Toxicity	4	Drugs For Treatment Of Tuberculosis	Tuberculosis
rs2031920	Other	3	sevoflurane
rs2070673	Toxicity	3	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin	Leukemia;Myeloid;Acute
rs2070676	Efficacy,Toxicity	3	cisplatin;cyclophosphamide	Ovarian Neoplasms
rs2515641	Toxicity	3	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin	Leukemia;Myeloid;Acute
rs2515641	Efficacy	3	risperidone	Schizophrenia
rs3813867	Other	3	sevoflurane
rs6413432	Efficacy	3	cisplatin;cyclophosphamide	Ovarian Neoplasms

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2031920	CYP2E1, DUX1	3	1.50	4	Drugs For Treatment Of Tuberculosis;ethanol;sevoflurane
rs2070672	CYP2E1		0.00	0
rs2070673	CYP2E1, DUX1	3	2.75	1	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin
rs2070676	CYP2E1	3	1.25	1	cisplatin;cyclophosphamide
rs2515641	CYP2E1	3	2.75	2	cytarabine;fludarabine;gemtuzumab ozogamicin;idarubicin;risperidone
rs3813867	CYP2E1	3	1.50	2	sevoflurane
rs6413432	CYP2E1, DUX1	3	1.75	1	cisplatin;cyclophosphamide
rs8192766	CYP2E1		0.00	0
rs6413420	CYP2E1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP2 family: drug metabolising subset

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 23 [PMID: 17125252]	Inhibition	7.4	pKi
12-Imidazolyl-1-dodecanol	Inhibition	6.2	pKi

Binding affinities (BindingDB)

1 measured of 16 human assays (17 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(3-Nitro-phenyl)-3-{2-[4-(pyridin-2-ylamino)-butyrylamino]-acetylamino}-propionic acid	IC50	850 nM	US-9173935: Phospholipid drug analogs

ChEMBL bioactivities

71 potent at pChembl≥5 of 144 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Ki	40	nM	CHEMBL215134
7.30	Ki	50	nM	CHEMBL214784
7.05	IC50	90	nM	CHEMBL214784
6.70	Ki	200	nM	CHEMBL386124
6.64	IC50	230	nM	CHEMBL4161819
6.60	IC50	251.2	nM	CHEMBL601428
6.36	IC50	440	nM	CHEMBL386124
6.24	IC50	580	nM	CHEMBL178780
6.22	Ki	600	nM	CHEMBL215174
6.16	IC50	700	nM	CHEMBL3330409
6.10	Ki	800	nM	CHEMBL214859
6.10	Ki	800	nM	CHEMBL214990
6.07	IC50	860	nM	CHEMBL178711
6.07	IC50	850	nM	CHEMBL9737
6.07	IC50	850	nM	DITIOCARB
6.05	IC50	900	nM	CHEMBL3330410
6.04	IC50	920	nM	CHEMBL4173133
5.96	IC50	1100	nM	CHEMBL178708
5.96	IC50	1100	nM	CHEMBL2130955
5.89	IC50	1300	nM	CHEMBL4169324
5.82	IC50	1500	nM	CHEMBL4165249
5.82	IC50	1500	nM	CHEMBL214990
5.72	IC50	1900	nM	CHEMBL4163694
5.72	IC50	1900	nM	CHEMBL4169721
5.72	IC50	1900	nM	CHEMBL2130955
5.70	Ki	2000	nM	CHEMBL360999
5.70	IC50	2000	nM	CHEMBL4176100
5.60	IC50	2500	nM	CHEMBL5612347
5.55	IC50	2800	nM	CHEMBL2130955
5.51	Ki	3100	nM	CHEMBL179704
5.51	IC50	3100	nM	CHEMBL4168669
5.46	Ki	3500	nM	CHEMBL179669
5.43	IC50	3700	nM	CHEMBL5406721
5.43	IC50	3700	nM	CHEMBL46909
5.42	IC50	3800	nM	CHEMBL5418617
5.41	IC50	3900	nM	CHEMBL5429178
5.39	IC50	4100	nM	CHEMBL360999
5.39	IC50	4100	nM	CHEMBL179618
5.39	IC50	4100	nM	CHEMBL179399
5.38	IC50	4200	nM	CHEMBL178534
5.38	IC50	4200	nM	CHEMBL4174365
5.35	IC50	4500	nM	CHEMBL4172462
5.31	IC50	4900	nM	CHEMBL2130955
5.30	IC50	5000	nM	CHEMBL593763
5.28	Ki	5200	nM	CHEMBL218397
5.26	IC50	5500	nM	CHEMBL4160749
5.23	IC50	5900	nM	CHEMBL4162449
5.23	IC50	5900	nM	CHEMBL5406218
5.22	IC50	6053	nM	CHEMBL65590
5.20	IC50	6300	nM	CHEMBL179704

PubChem BioAssay actives

66 with measured affinity, of 854 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
(5-phenylthiophen-2-yl)methanamine	272639: Inhibition of human CYP2E1	ki	0.0400	uM
(5-pyridin-3-ylfuran-2-yl)methanethiol	272639: Inhibition of human CYP2E1	ki	0.0500	uM
S-[(5-pyridin-3-ylfuran-2-yl)methyl] ethanethioate	272639: Inhibition of human CYP2E1	ki	0.2000	uM
[5-(4-ethyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.2300	uM
N-(4-chlorophenyl)-5-ethyl-N-methyl-3-phenyl-1,2-oxazole-4-carboxamide	2108148: Inhibition of CYP450 (unknown origin)	ic50	0.2512	uM
3-(1-benzylimidazol-4-yl)pyridine	241649: Inhibitory concentration value against human cytochrome P-450 2E1	ic50	0.5800	uM
3-[5-(1,3-dithiolan-2-yl)furan-2-yl]pyridine	272639: Inhibition of human CYP2E1	ki	0.6000	uM
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.7000	uM
(5-phenylfuran-2-yl)methanamine	272639: Inhibition of human CYP2E1	ki	0.8000	uM
3-[5-(methylsulfanylmethyl)furan-2-yl]pyridine	272639: Inhibition of human CYP2E1	ki	0.8000	uM
1-(5-pyridin-3-ylthiophen-2-yl)-N-[(5-pyridin-3-ylthiophen-2-yl)methyl]methanamine	241649: Inhibitory concentration value against human cytochrome P-450 2E1	ic50	0.8600	uM
2-pyrrolidin-1-yl-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]-2-thiophen-3-ylacetamide	2119433: Inhibition of CYP450 (unknown origin)	ic50	0.9000	uM
[5-(4-ethyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.9200	uM
2-[4-(trifluoromethyl)phenyl]chromen-4-one	1860369: Inhibition of CYP450 in human HCT-116 cells assessed as 20-HETE formation in presence of arachidonic acid incubated for 15 mins by multi-enzyme assay based LC-MS/MS analysis	ic50	1.1000	uM
[5-[4-(furan-3-yl)-3-pyridinyl]furan-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.3000	uM
[(E)-hex-3-enyl] pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	1.3000	uM
hexyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	1.4000	uM
[5-(4-propyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.5000	uM
cyclopentylmethyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	1.6000	uM
12-imidazol-1-yldodecanoic acid	1799788: Binding Assay from Article 10.1074/jbc.M110.109017: “Human cytochrome P450 2E1 structures with fatty acid analogs reveal a previously unobserved binding mode.”	kd	1.8000	uM
5-methylhexyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	1.8000	uM
[5-(4-propyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.9000	uM
3-[4-(furan-2-yl)-3-pyridinyl]prop-2-yn-1-amine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	1.9000	uM
3-(1-methylimidazol-4-yl)pyridine	272639: Inhibition of human CYP2E1	ki	2.0000	uM
[5-(4-methyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	2.0000	uM
octyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	2.1000	uM
4-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-N-[[(7R)-5,6,7,8-tetrahydro-1,6-naphthyridin-7-yl]methyl]cyclohexane-1,4-diamine	2124397: Inhibition of CYP450 (unknown origin)	ic50	2.5000	uM
3-methylpentyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	2.6000	uM
3-(4-methylthiophen-3-yl)pyridine	272639: Inhibition of human CYP2E1	ki	3.1000	uM
[5-[4-(furan-2-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	3.1000	uM
3-(3-methylthiophen-2-yl)pyridine	272639: Inhibition of human CYP2E1	ki	3.5000	uM
1-[3-(2,4-dimethoxyphenyl)phenyl]-2,4-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
1-[(E)-2-(2,4-dimethoxyphenyl)ethenyl]-3,5-dimethoxybenzene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.7000	uM
2,4-bis(3,5-dimethoxyphenyl)pyrimidine	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.8000	uM
2,5-bis(3,5-dimethoxyphenyl)thiophene	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	3.9000	uM
3-(3-methyl-1H-imidazol-3-ium-4-yl)pyridine	241649: Inhibitory concentration value against human cytochrome P-450 2E1	ic50	4.1000	uM
3-thiophen-2-ylpyridine	241649: Inhibitory concentration value against human cytochrome P-450 2E1	ic50	4.1000	uM
(NE)-N-[(5-pyridin-3-ylthiophen-2-yl)methylidene]hydroxylamine	241649: Inhibitory concentration value against human cytochrome P-450 2E1	ic50	4.2000	uM
3-[4-(furan-3-yl)-3-pyridinyl]prop-2-yn-1-amine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	4.2000	uM
[5-(4-methoxy-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	4.5000	uM
7-[(3-chlorophenyl)methoxy]-4-(methylaminomethyl)chromen-2-one;methanesulfonic acid	439571: Inhibition of human recombinant CYP2E1	ic50	5.0000	uM
3-(1H-pyrazol-5-yl)pyridine	272639: Inhibition of human CYP2E1	ki	5.2000	uM
[5-[4-(furan-3-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	5.5000	uM
[5-(4-methoxy-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	5.9000	uM
4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]phenol	1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysis	ic50	5.9000	uM
pentyl pyridine-3-carboxylate	1799818: Spectral Binding Assay from Article 10.1002/cbic.201200524: “Type II Ligands as Chemical Auxiliaries To Favor Enzymatic Transformations by P450 2E1.”	kd	5.9000	uM
1-pyridin-4-yl-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalen-4-ol	2022025: Inhibition of CYP450 in human liver microsomes	ic50	6.0534	uM
[5-(4-phenyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	6.8000	uM
[5-(4-phenyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356010: Inhibition of CYP2E1 in human liver microsomes using chlorzoxazone as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	7.0000	uM

CTD chemical–gene interactions

405 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Ethanol	affects reaction, decreases phosphorylation, decreases abundance, increases response to substance, affects activity (+15 more)	39
Chlorzoxazone	decreases activity, decreases metabolic processing, decreases reaction, increases metabolic processing, increases chemical synthesis (+6 more)	33
Benzene	increases oxidation, decreases methylation, increases expression, affects chemical synthesis, increases metabolic processing (+4 more)	18
4-nitrophenol	increases reaction, increases hydroxylation, increases chemical synthesis, affects binding, decreases reaction (+2 more)	15
Dimethylnitrosamine	decreases methylation, affects reaction, increases reaction, increases mutagenesis, affects metabolic processing (+9 more)	14
Acetaminophen	increases metabolic processing, affects reaction, decreases reaction, affects cotreatment, decreases expression (+2 more)	13
Styrene	affects oxidation, increases metabolic processing, affects activity, decreases reaction, affects reaction (+7 more)	12
Fomepizole	decreases metabolic processing, increases expression, increases degradation, affects metabolic processing, increases metabolic processing (+5 more)	10
Toluene	affects methylation, affects reaction, affects activity, decreases methylation, increases expression (+3 more)	10
Vinyl Chloride	increases metabolic processing, affects response to substance, increases mutagenesis, affects metabolic processing, increases oxidation (+4 more)	10
aniline	decreases activity, affects cotreatment, affects metabolic processing, increases hydroxylation, increases metabolic processing (+3 more)	8
allyl sulfide	increases response to substance, increases activity, decreases activity, decreases reaction, increases expression (+2 more)	8
Tetrachlorodibenzodioxin	affects cotreatment, affects expression, increases expression, decreases expression, decreases reaction (+1 more)	8
6-hydroxychlorzoxazone	increases chemical synthesis, increases metabolic processing, increases hydroxylation, decreases reaction	7
Ditiocarb	decreases reaction, increases glutathionylation, increases metabolic processing, affects cotreatment, increases response to substance (+1 more)	7
Disulfiram	increases metabolic processing, increases oxidation, increases expression, decreases activity, affects activity (+2 more)	7
Trichloroethylene	increases activity, increases response to substance, affects metabolic processing, affects response to substance, increases metabolic processing (+2 more)	7
Diethylnitrosamine	increases activity, increases reaction, affects metabolic processing, affects cotreatment, increases response to substance	6
Dimethyl Sulfoxide	affects expression, decreases reaction, increases degradation, increases expression, increases reaction	6
Isoniazid	increases metabolic processing, increases response to substance, decreases reaction, decreases activity, increases expression (+2 more)	6
Plant Extracts	decreases activity, decreases expression, decreases reaction, increases abundance, increases expression (+1 more)	6
Arachidonic Acid	decreases reaction, increases expression, increases reaction, increases response to substance, affects cotreatment (+3 more)	6
Acrylamide	affects cotreatment, affects metabolic processing, affects response to substance, affects expression, increases expression (+2 more)	6
perfluorooctane sulfonic acid	decreases reaction, increases oxidation, decreases activity, decreases expression	5
Benzo(a)pyrene	increases mutagenesis, affects response to substance, affects methylation, decreases expression, increases expression (+1 more)	5
Carbon Tetrachloride	increases degradation, increases reaction, increases activity, decreases activity, increases metabolic processing (+2 more)	5
Dimethylformamide	increases abundance, affects metabolic processing, increases metabolic processing, increases oxidation, increases expression	5
N-nitroso(di-n-propyl)amine	increases activity, increases reaction, affects metabolic processing, affects cotreatment, increases response to substance	4
3-xylene	increases hydrolysis, increases metabolic processing, increases oxidation, decreases reaction, increases expression	4
Glutathione	affects binding, increases reaction, decreases reaction, increases response to substance, affects cotreatment (+3 more)	4

ChEMBL screening assays

393 unique, capped per target: 388 admet, 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060324	ADMET	Inhibition of CYP450	Rapid identification of ETP-46992, orally bioavailable PI3K inhibitor, selective versus mTOR. — Bioorg Med Chem Lett
CHEMBL4614611	Binding	Drug metabolism in human liver microsomes assessed as Cytochrome P450-mediated formation of 12-OHNVP by measuring Kcat/Km ratio in presence of NADPH regenerating reagents by uHPLC-MS/MS analysis	Twelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death. — J Med Chem

Cellosaurus cell lines

19 cell lines: 7 spontaneously immortalized cell line, 7 cancer cell line, 5 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_5332	MCL-5	Transformed cell line	Male
CVCL_5A60	V79MZh2E1/hSULT1A1	Spontaneously immortalized cell line	Male
CVCL_A2GU	V79MZh2E1	Spontaneously immortalized cell line	Male
CVCL_A2HB	Hep G2-MV2E1-9	Cancer cell line	Male
CVCL_A2HF	Hep G2-E43	Cancer cell line	Male
CVCL_A2HG	Hep G2-E47	Cancer cell line	Male
CVCL_A2HH	HepG2-CYP2E1	Cancer cell line	Male
CVCL_A5CT	Hep-G2 VL-17A	Cancer cell line	Male
CVCL_B5W3	Hepc/2E1.3-8	Cancer cell line	Male
CVCL_D9CW	Ubigene HEK293 CYP2E1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial