CYP2A6

Summary

CYP2A6 (cytochrome P450 family 2 subfamily A member 6, HGNC:2610) is a protein-coding gene on chromosome 19q13.2, encoding Cytochrome P450 2A6 (P11509). Exhibits a high coumarin 7-hydroxylase activity.

This gene, CYP2A6, 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 its expression is induced by phenobarbital. The enzyme is known to hydroxylate coumarin, and also metabolizes nicotine, aflatoxin B1, nitrosamines, and some pharmaceuticals. Individuals with certain allelic variants are said to have a poor metabolizer phenotype, meaning they do not efficiently metabolize coumarin or nicotine. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.

Source: NCBI Gene 1548 — RefSeq curated summary.

At a glance

• Gene–disease (curated): coumarin resistance (No Known Disease Relationship, GenCC) — +1 more curated relationship
• GWAS associations: 77
• Clinical variants (ClinVar): 97 total
• Phenotypes (HPO): 6
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000762

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2610
Approved symbol	CYP2A6
Name	cytochrome P450 family 2 subfamily A member 6
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CPA6, CYP2A
Ensembl gene	ENSG00000255974
Ensembl biotype	protein_coding
OMIM	122720
Entrez	1548

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000301141, ENST00000596719, ENST00000599960, ENST00000600495, ENST00000874213, ENST00000874214, ENST00000874215, ENST00000874216, ENST00000874217, ENST00000874218, ENST00000874219, ENST00000874220, ENST00000874221, ENST00000874222, ENST00000874223

RefSeq mRNA: 1 — MANE Select: NM_000762 NM_000762

CCDS: CCDS12568

Canonical transcript exons

ENST00000301141 — 9 exons

Exon	Start	End
ENSE00001789088	40850247	40850447
ENSE00002436864	40845294	40845481
ENSE00002489819	40844631	40844772
ENSE00003006113	40843541	40843977
ENSE00003462957	40849818	40849980
ENSE00003490034	40845956	40846097
ENSE00003545561	40846875	40847051
ENSE00003565479	40848614	40848763
ENSE00003685949	40848219	40848379

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 98.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4302 / max 548.1739, expressed in 14 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181016	1.4143	14
181015	0.0159	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.57	gold quality
liver	UBERON:0002107	96.64	gold quality
paraflocculus	UBERON:0005351	95.08	gold quality
middle frontal gyrus	UBERON:0002702	94.84	gold quality
frontal pole	UBERON:0002795	94.48	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.49	gold quality
nasal cavity epithelium	UBERON:0005384	89.91	gold quality
endometrium epithelium	UBERON:0004811	87.21	gold quality
cerebellar vermis	UBERON:0004720	84.95	silver quality
cervix squamous epithelium	UBERON:0006922	83.36	gold quality
olfactory bulb	UBERON:0002264	83.31	gold quality
type B pancreatic cell	CL:0000169	83.21	gold quality
male germ cell	CL:0000015	80.93	silver quality
tendon of biceps brachii	UBERON:0008188	80.72	gold quality
sperm	CL:0000019	80.56	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.80	gold quality
tongue squamous epithelium	UBERON:0006919	79.57	gold quality
lateral globus pallidus	UBERON:0002476	79.53	gold quality
triceps brachii	UBERON:0001509	78.81	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.09	silver quality
vena cava	UBERON:0004087	77.94	gold quality
endothelial cell	CL:0000115	77.63	gold quality
thymus	UBERON:0002370	77.55	silver quality
gluteal muscle	UBERON:0002000	77.46	silver quality
epithelium of bronchus	UBERON:0002031	77.39	silver quality
layer of synovial tissue	UBERON:0007616	77.34	gold quality
bronchus	UBERON:0002185	77.30	silver quality
trachea	UBERON:0003126	77.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.92	silver quality
globus pallidus	UBERON:0001875	76.79	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, ESR1, HNF4A, NFE2L2, NFIA, NFIC, NFYA, NR1I2, NR3C1, POU2F1, TCF3, UBP1

miRNA regulators (miRDB)

5 targeting CYP2A6, 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-6515-3P	99.82	68.19	1933
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-558	97.50	67.16	977
HSA-MIR-103B	95.51	66.85	441

Literature-anchored findings (GeneRIF, showing 40)

• Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. (PMID:11805739)
• CYP2A6 activity, measured by urinary caffeine metabolite ratio, strongly related to colorectal cancer risk (PMID:11927498)
• CYP2A6 gene deletion reduces oral cancer risk in betel quid chewers in Sri Lanka (PMID:11960911)
• CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism (PMID:11960914)
• CTY2A6 deletion is associated with gastric adenocarcinoma among Japanese populations. (PMID:12115524)
• The metabolism of coumarin via 7-hydroxylation in the human (CYP2A6) and mouse (CYP2A5) enzymes is explained in terms of molecular modelling of the active site interactions. (PMID:12162851)
• D-type is a genotype heterozygous for the CYP2A6*4A and another novel entire CYP2A6 gene-deleted allele, CYP2A6*4B (PMID:12172220)
• genetic variation of CYP2A6 and its resulting effects on metabolism and health consequences [review] (PMID:12406643)
• Despite the possible protection against active smoking behavior in subjects homozygous for the deletion allele, the CYP2A6 polymorphism has only a limited impact on public health because no protective effect was found in heterozygous subjects. (PMID:12749606)
• The mutation in the TATA box (CYP2A6*9 allele) caused the decreased in vivo enzymatic activity; the CYP2A6*9 allele caused the decreased expression level and enzymatic activity of CYP2A6 in human liver. (PMID:12844137)
• For the first time CYP2A6 is reported as a hepatic autoantigen in patients with viral hepatitis caused by flaviviruses and in particular in HCV/anti-LKM-1 positive patients. (PMID:14568264)
• Polymorphism in the promoter region of the CYPA6 reduced the expression levels of CYP2A6 mRNA and protein in liver, resulting in the decrease of coumarin-7-hydroxylase activities. (PMID:14583682)
• In this study it was suggested that the CYP2A6AST;4C allele may prevent the carrier from smoking and the CYP2A6AST;1A/AST;1B heterozygote may be at risk for developing smoking behavior. (PMID:14981342)
• A method that can distinguish between CYP2A6*4A, CYP2A6*4D, and CYP2A6*1F which could otherwise cause a mistyping as CYP2A6*4D. (PMID:15225612)
• CYP2A6 genetic polymorphisms is associated with smoking behavior and tobacco-related lung cancer risk (PMID:15308589)
• Identification of deletion-junction site of CYP2A6*4B allele lacking entire coding region of CYP2A6 in Japanese. (PMID:15454735)
• CYP2A6 has a role in rate of nicotine metabolism in adult Caucasians (PMID:15475735)
• Kinetic analysis of oxidation of coumarins by human cytochrome P450 2A6 (PMID:15665333)
• Constitutive hepatic expression of CYP2A6 is governed by an interplay between the transcription factors HNF-4alpha, C/EBPalpha, C/EBPbeta, and Oct-1. (PMID:15671201)
• CYP2A6 has some genetic influence on nicotine metabolism (PMID:15861035)
• analysis of CYP2A6*7, CYP2A6*8 and CYP2A6*10 assessed with a novel haplotyping method in different ethnic populations (PMID:15861044)
• CYP2A6*1B is associated with the number of cigarettes smoked per day. (PMID:15940289)
• analysis of CYP2A6 phenotype variants in Caucasians (PMID:16041240)
• CYP2A6 structure shows a compact, hydrophobic active site with one hydrogen bond donor, Asn297, that orients coumarin for regioselective oxidation (PMID:16086027)
• In the first CYP2A6 transgenic mouse model, systemic clearance of coumarin is significantly higher in CYP2A6 transgenic mice than in C57BL controls, consistent with the predicted role of CYP2A6 as the major coumarin hydroxylase in human liver. (PMID:16126166)
• Subjects carrying the CYP2A6*4C allele have lower risk of tobacco-related lung cancer; epidemiological studies indicate that smokers homozygous for the CYP2A6*4C allele show much lower odds ratios toward cancer risk. (PMID:16176798)
• analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 (PMID:16207711)
• The CYP2A6*9 allele was significantly more frequent in Maori smokers (70%) compared to Europeans (30%). The Maori smokers also demonstrated a reduced metabolic rate and reduced nicotine intake. (PMID:16372023)
• The 3’-UTR of CYP2A6 has a pronounced effect on gene expression and stability of corresponding mRNA and enzyme expression (PMID:16378601)
• CYP2A6 genotypes are related with nicotine dependence, influencing smoking habits and withdrawal symptoms in quitting smoking. (PMID:16402086)
• Findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, nicotine replacement therapy. (PMID:16402128)
• no substantial differences in nicotine metabolism between those without the variant (CYP2A6*1/*1, n = 163) and those with the variant (CYP2A6*1/*21, n = 9) (PMID:16758265)
• CYP2A6 is induced via PXR and PGC-1alpha through the DR4-like element at the distal response region. (PMID:16857725)
• A statistically significant high frequency of the duplicated CYP2A6*1x2 allele occurred among Chinese. Among Malays and Chinese, the most common allele was CYP2A6*1B, but it was CYP2A6*1A among Indians. (PMID:16891249)
• Results will enhance the interpretation of CYP2A6 genotypic data as used in association studies of smoking behavior and its health consequences. (PMID:17112802)
• comparison of substrate dynamics in CYP2E1 and CYP2A6 (PMID:17156750)
• De novo formation of indican in transgenic tobacco plants hampered indigo formation, it supports the contention that biosynthetic pathways can be efficiently mimicked by metabolic engineering of this protein. (PMID:17207267)
• Results demonstrate that in vivo phenotyping of CYP2A6 using nicotine and coumarin are not metabolically equivalent. (PMID:17220563)
• identification of a novel CYP2A6 gene duplication created through an unequal crossover with the CYP2A7 gene; findings suggest the duplicated allele, which is specific for African Americans, would increase nicotine metabolism & may affect smoking behavior (PMID:17267622)
• study investigated the association of CYP2A6 genotype with smoking topography (PMID:17454707)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cyp2a5	ENSMUSG00000005547
mus_musculus	Cyp2a12	ENSMUSG00000060407
mus_musculus	Cyp2a4	ENSMUSG00000074254
mus_musculus	Cyp2a22	ENSMUSG00000091867
rattus_norvegicus	Cyp2a1	ENSRNOG00000020817
rattus_norvegicus	Cyp2a3	ENSRNOG00000068556
rattus_norvegicus	Cyp2a2	ENSRNOG00000069320

Paralogs (15): CYP2W1 (ENSG00000073067), CYP2D6 (ENSG00000100197), CYP2C18 (ENSG00000108242), CYP2E1 (ENSG00000130649), CYP2J2 (ENSG00000134716), CYP2C9 (ENSG00000138109), CYP2C8 (ENSG00000138115), CYP2U1 (ENSG00000155016), CYP2C19 (ENSG00000165841), CYP2S1 (ENSG00000167600), CYP2R1 (ENSG00000186104), CYP2B6 (ENSG00000197408), CYP2F1 (ENSG00000197446), CYP2A13 (ENSG00000197838), CYP2A7 (ENSG00000198077)

Protein

Protein identifiers

Cytochrome P450 2A6 — P11509 (reviewed: P11509)

Alternative names: 1,4-cineole 2-exo-monooxygenase, CYPIIA6, Coumarin 7-hydroxylase, Cytochrome P450 IIA3, Cytochrome P450(I)

All UniProt accessions (2): P11509, M0R2Z4

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Liver.

Induction. By phenobarbital and dexamethasone.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR008067	Cyt_P450_E_grp-I_CYP2A-like	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050182	Cytochrome_P450_fam2	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.14.1 — unspecific monooxygenase (BRENDA: 53 organisms, 363 substrates, 53 inhibitors, 69 Km, 40 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
FENTHION	0.0016–0.131	18
NADH	0.004–1.43	13
NADPH	0.002–0.13	6
(1R)-CIS-PERMETHRIN	0.055–0.061	2
(1R)-TRANS-PERMETHRIN	0.115–0.131	2
(1S)-CIS-PERMETHRIN	0.057–0.063	2
(1S)-TRANS-PERMETHRIN	0.101–0.106	2
7-ETHOXYRESORUFIN	0.0001–0.0012	2
MYRISTIC ACID	0.023–0.11	2
OLEIC ACID	0.075–0.084	2
OMEGA-(P-NITROPHENYL)DECANOIC ACID	0.0064–0.0245	2
OMEGA-(P-NITROPHENYL)DODECANOIC ACID	0.0065–0.0104	2
OMEGA-(P-NITROPHENYL)OCTANOIC ACID	0.0319–0.0618	2
12-METHYL-TETRADECANOIC ACID	0.0129	1
13-METHYL-TETRADECANOIC ACID	0.0165	1

Catalyzed reactions (Rhea), 1 shown:

• 1,4-cineole + reduced [NADPH–hemoprotein reductase] + O2 = 2-exo-hydroxy-1,4-cineole + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:49160)

UniProt features (75 total): sequence variant 23, helix 20, strand 13, mutagenesis site 6, turn 6, binding site 3, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2FDV	X-RAY DIFFRACTION	1.65
2FDU	X-RAY DIFFRACTION	1.85
1Z10	X-RAY DIFFRACTION	1.9
2FDY	X-RAY DIFFRACTION	1.95
1Z11	X-RAY DIFFRACTION	2.05
2FDW	X-RAY DIFFRACTION	2.05
3T3Q	X-RAY DIFFRACTION	2.1
3EBS	X-RAY DIFFRACTION	2.15
4EJJ	X-RAY DIFFRACTION	2.3
3T3R	X-RAY DIFFRACTION	2.4
4RUI	X-RAY DIFFRACTION	2.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11509-F1	96.70	0.93

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 (3): 107; 297; 439 (axial binding residue)

Mutagenesis-validated functional residues (6):

Position	Phenotype
208	increases phenacetin o-deethylation activity 10 fold; when associated with f-300 and a-301. increases phenacetin o-deeth
213	no effect on phenacetin o-deethylation activity.
300	increases phenacetin o-deethylation activity 3 fold. increases phenacetin o-deethylation activity 8 fold; when associate
301	slightly decreases phenacetin o-deethylation activity. increases phenacetin o-deethylation activity 8 fold; when associa
369	increases phenacetin o-deethylation activity 3 fold. increases phenacetin o-deethylation activity 38 fold; when associat
372	increases phenacetin o-deethylation activity 2 fold.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions

MSigDB gene sets: 274 (showing top): AP1_01, REACTOME_BIOLOGICAL_OXIDATIONS, BENPORATH_ES_WITH_H3K27ME3, GOMF_METALLOPEPTIDASE_ACTIVITY, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GNF2_GSTM1, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GNF2_HPN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, CAGCTG_AP4_Q5, UEDA_PERIFERAL_CLOCK, SMID_BREAST_CANCER_LUMINAL_B_UP, GNF2_LCAT, BACH2_01

GO Biological Process (7): xenobiotic metabolic process (GO:0006805), steroid metabolic process (GO:0008202), coumarin metabolic process (GO:0009804), epoxygenase P450 pathway (GO:0019373), xenobiotic catabolic process (GO:0042178), coumarin catabolic process (GO:0046226), lipid metabolic process (GO:0006629)

GO Molecular Function (11): iron ion binding (GO:0005506), coumarin 7-hydroxylase activity (GO:0008389), arachidonate epoxygenase activity (GO:0008392), 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), enzyme binding (GO:0019899), heme binding (GO:0020037), monooxygenase activity (GO:0004497), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (5): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytoplasmic microtubule (GO:0005881), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	1
Xenobiotics	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
oxidoreductase activity	2
cellular anatomical structure	2
cytoplasm	2
metabolic process	1
cellular response to xenobiotic stimulus	1
lipid metabolic process	1
phenylpropanoid metabolic process	1
arachidonate metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
coumarin metabolic process	1
phenylpropanoid catabolic process	1
primary metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
protein binding	1
tetrapyrrole binding	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
microtubule	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CYP2A6	RABAC1	psi-mi:“MI:0915”(physical association)	0.590
	CYP2A6	psi-mi:“MI:0407”(direct interaction)	0.560
	CYP2A6	psi-mi:“MI:0210”(hydroxylation reaction)	0.560
	CYP2A6	psi-mi:“MI:0945”(oxidoreductase activity electron transfer reaction)	0.440
CYP2A7	CYP2A6	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): CYP2A6 (Affinity Capture-MS), RABAC1 (Affinity Capture-MS), RABAC1 (Affinity Capture-MS), CYP2A6 (Positive Genetic), TRO (Cross-Linking-MS (XL-MS)), EBNA1BP2 (Cross-Linking-MS (XL-MS)), ANXA2 (Cross-Linking-MS (XL-MS)), CYP2A6 (Affinity Capture-MS), CYP2A6 (Affinity Capture-MS), CYP2A6 (Reconstituted Complex), POR (Reconstituted Complex), CYP2A6 (Reconstituted Complex)

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: A0A067DE75, A0A067ELB0, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1I9Q5Z0, A0A2Z5TMB8, A0A3Q7HBJ5, A0A3Q7HS74, A0A517FNC5, A0AAW1JA93, A0AAW1NEA3, A2A974, A2RRT9, A2Z212, A5BFI4, B8QHP3, C0SJS2, E9Q5K4, F5BHA2, F6H9N6, H2DH16, I7C6E8, I7CT85, K4CEE8, K4CI52, O15528, O18993, O35084, O35132, O35728, O42563, O49340, O65785, O65786, O70537, O88833, O93323, P0DXH8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	10
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1452 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40845291:CACC:C	donor_loss	1.0000
19:40845325:T:TA	donor_gain	1.0000
19:40845477:CTTGG:C	acceptor_gain	1.0000
19:40845478:TTGG:T	acceptor_gain	1.0000
19:40845479:TGG:T	acceptor_gain	1.0000
19:40845480:GG:G	acceptor_gain	1.0000
19:40845482:C:CC	acceptor_gain	1.0000
19:40845482:C:CG	acceptor_loss	1.0000
19:40845954:AC:A	donor_gain	1.0000
19:40845955:CC:C	donor_gain	1.0000
19:40845974:T:TA	donor_gain	1.0000
19:40846093:TCCTC:T	acceptor_gain	1.0000
19:40846094:CCTCC:C	acceptor_gain	1.0000
19:40846095:CTC:C	acceptor_gain	1.0000
19:40846096:TC:T	acceptor_gain	1.0000
19:40846097:CC:C	acceptor_gain	1.0000
19:40846098:C:CA	acceptor_loss	1.0000
19:40846098:C:CC	acceptor_gain	1.0000
19:40846870:TGTAC:T	donor_loss	1.0000
19:40846871:GTAC:G	donor_loss	1.0000
19:40846872:TACC:T	donor_loss	1.0000
19:40846873:ACCT:A	donor_gain	1.0000
19:40846873:ACCTC:A	donor_loss	1.0000
19:40846874:CCTC:C	donor_gain	1.0000
19:40846876:T:TA	donor_gain	1.0000
19:40847047:TAGAG:T	acceptor_gain	1.0000
19:40847058:T:C	acceptor_gain	1.0000
19:40847058:T:TC	acceptor_gain	1.0000
19:40848609:CTCA:C	donor_loss	1.0000
19:40848610:TCACC:T	donor_loss	1.0000

AlphaMissense

3281 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40844638:A:C	F432L	0.992
19:40844638:A:T	F432L	0.992
19:40844640:A:G	F432L	0.992
19:40844686:G:C	F416L	0.990
19:40844686:G:T	F416L	0.990
19:40844688:A:G	F416L	0.990
19:40848717:G:C	F130L	0.984
19:40848717:G:T	F130L	0.984
19:40848719:A:G	F130L	0.984
19:40849867:G:C	F98L	0.983
19:40849867:G:T	F98L	0.983
19:40849869:A:G	F98L	0.983
19:40844701:G:C	F411L	0.982
19:40844701:G:T	F411L	0.982
19:40844703:A:G	F411L	0.982
19:40845372:T:A	R361S	0.982
19:40845372:T:G	R361S	0.982
19:40845395:C:G	A354P	0.982
19:40846071:G:C	F286L	0.981
19:40846071:G:T	F286L	0.981
19:40846073:A:G	F286L	0.981
19:40845382:T:A	E358V	0.980
19:40843977:C:T	G435E	0.979
19:40846893:A:C	F271L	0.978
19:40846893:A:T	F271L	0.978
19:40846895:A:G	F271L	0.978
19:40845373:C:G	R361T	0.977
19:40843977:C:A	G435V	0.976
19:40844640:A:T	F432I	0.975
19:40845348:A:C	S369R	0.974

dbSNP variants (sampled 300 via entrez): RS1000639781 (19:40849061 A>C), RS1000975758 (19:40851324 C>T), RS1000991166 (19:40846651 T>C), RS1001006731 (19:40851643 C>A,G), RS1001522596 (19:40850521 C>T), RS1001863125 (19:40851730 G>A,T), RS1002350700 (19:40847268 G>A), RS1002622294 (19:40844106 A>G), RS1002919687 (19:40844409 G>C), RS1003063000 (19:40843720 C>G,T), RS1004131513 (19:40844523 A>T), RS1007119077 (19:40850069 G>A,C), RS1007510552 (19:40846836 C>G,T), RS1008206975 (19:40846626 T>G), RS1008545693 (19:40847606 AG>A)

Disease associations

OMIM: gene MIM:122720 | disease phenotypes: MIM:122700

GenCC curated gene-disease

Disease	Classification	Inheritance
coumarin resistance	No Known Disease Relationship	Unknown
nicotine dependence	No Known Disease Relationship	Unknown

Mondo (2): coumarin resistance (MONDO:0007390), nicotine dependence (MONDO:0008575)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0006519	Alveolar cell carcinoma
HP:0030078	Lung adenocarcinoma
HP:0030358	Non-small cell lung carcinoma

GWAS associations

77 associations (top):

Study	Trait	p-value
GCST000666_5	Smoking behavior	1.000000e-08
GCST000667_2	Smoking behavior	2.000000e-12
GCST001321_2	Chronic obstructive pulmonary disease	3.000000e-09
GCST001696_1	Smoking behavior	4.000000e-42
GCST002525_20	Local histogram emphysema pattern	1.000000e-06
GCST002525_6	Local histogram emphysema pattern	1.000000e-09
GCST003071_3	Cerebrospinal P-tau181p levels	4.000000e-07
GCST003078_3	Cerebrospinal fluid p-Tau181p:AB1-42 ratio	2.000000e-06
GCST003262_426	Post bronchodilator FEV1	2.000000e-08
GCST003262_863	Post bronchodilator FEV1	3.000000e-07
GCST003264_1178	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_741	Post bronchodilator FEV1/FVC ratio	5.000000e-09
GCST003629_1	Nicotine metabolite ratio in current smokers	1.000000e-50
GCST003629_10	Nicotine metabolite ratio in current smokers	4.000000e-11
GCST003629_11	Nicotine metabolite ratio in current smokers	3.000000e-09
GCST003629_13	Nicotine metabolite ratio in current smokers	4.000000e-08
GCST003629_2	Nicotine metabolite ratio in current smokers	1.000000e-41
GCST003629_5	Nicotine metabolite ratio in current smokers	7.000000e-24
GCST003629_6	Nicotine metabolite ratio in current smokers	1.000000e-21
GCST003629_7	Nicotine metabolite ratio in current smokers	4.000000e-14
GCST003847_2	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) level)	6.000000e-08
GCST003849_1	Caffeine metabolism (plasma 3,7-dimethylxanthine (theobromine) level)	4.000000e-06
GCST003851_10	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_11	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	8.000000e-09
GCST003851_12	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-10
GCST003851_13	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST003851_14	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-10
GCST003851_15	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-11
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-11

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0005850	emphysema pattern measurement
EFO:0004763	p-tau measurement
EFO:0007709	p-tau:beta-amyloid 1-42 ratio measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0007794	nicotine metabolite ratio
EFO:0007872	caffeine metabolite measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0007796	parental longevity
EFO:0008328	chronotype measurement
EFO:0006525	cigarettes per day measurement
EFO:0010089	bitter beverage consumption measurement
EFO:0010093	bitter non-alcoholic beverage consumption measurement
EFO:0006781	coffee consumption measurement
EFO:0009282	sodium measurement
EFO:0009115	tobacco smoke exposure measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0010091	tea consumption measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0006527	smoking status measurement
EFO:0004319	smoking cessation

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D014029	Tobacco Use Disorder	C25.775.912; F03.900.912
C563039	Coumarin Resistance (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523986 (PROTEIN FAMILY), CHEMBL5282 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,180,785 (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
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL3	NICOTINE	4	184,969
CHEMBL3989843	TRANYLCYPROMINE	4	70
CHEMBL405	AMPHETAMINE	4	68,439
CHEMBL416	METHOXSALEN	4	19,665
CHEMBL5416410	DASATINIB	4	655
CHEMBL550	PILOCARPINE	4	37,191
CHEMBL64	ISONIAZID	4	145,319
CHEMBL24171	BERGAPTEN	3	3,967
CHEMBL74415	CANNABINOL	3	18,794
CHEMBL16293	NAPHTHALENE	1	492,023
CHEMBL164660	PSORALEN	1	38,921
CHEMBL46730	PHENANTHRENE	1	128,853

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

PharmGKB clinical annotations

45 annotations.

Variant	Type	Level	Drugs	Phenotypes
CYP2A61, CYP2A615, CYP2A621, CYP2A622	Metabolism/PK	3	methoxsalen
CYP2A61, CYP2A61x2, CYP2A6*2	Toxicity	3	nicotine	Tobacco Use Disorder
CYP2A61, CYP2A61x2, CYP2A62, CYP2A64, CYP2A67, CYP2A69, CYP2A610, CYP2A611, CYP2A612, CYP2A613, CYP2A614, CYP2A615, CYP2A617, CYP2A619, CYP2A620, CYP2A623, CYP2A624, CYP2A625, CYP2A626, CYP2A627, CYP2A628, CYP2A635, CYP2A638, CYP2A639, CYP2A641, CYP2A646, CYP2A6*55	Metabolism/PK	1B	nicotine	Tobacco Use Disorder
CYP2A61, CYP2A61x2, CYP2A62, CYP2A64, CYP2A69, CYP2A612, CYP2A617, CYP2A620, CYP2A623, CYP2A624, CYP2A625, CYP2A626, CYP2A627, CYP2A628, CYP2A635, CYP2A646	Toxicity	3	nicotine	Tobacco Use Disorder
CYP2A61, CYP2A62, CYP2A64, CYP2A67, CYP2A69, CYP2A612, CYP2A617, CYP2A620, CYP2A623, CYP2A635, CYP2A6*46	Metabolism/PK	3	letrozole	Breast Neoplasms
CYP2A61, CYP2A62, CYP2A64, CYP2A67, CYP2A69, CYP2A646	Dosage	3	nicotine	Tobacco Use Disorder
CYP2A61, CYP2A62, CYP2A64, CYP2A69, CYP2A6*12	Toxicity	3	nicotine	Tobacco Use Disorder
CYP2A61, CYP2A62, CYP2A69, CYP2A617	Metabolism/PK	3	metronidazole
CYP2A61, CYP2A64, CYP2A65, CYP2A66, CYP2A67, CYP2A69, CYP2A610, CYP2A612, CYP2A617, CYP2A618, CYP2A619, CYP2A620	Metabolism/PK	3	coumarin
CYP2A61, CYP2A64, CYP2A67, CYP2A69, CYP2A610, CYP2A611, CYP2A618, CYP2A619, CYP2A6*46	Metabolism/PK	3	tegafur	Neoplasms
rs111869995	Metabolism/PK	3	nicotine
rs1302192284	Metabolism/PK	3	nicotine
rs1303839356	Metabolism/PK	3	nicotine
rs137904044	Metabolism/PK	3	nicotine
rs145014075	Metabolism/PK	3	nicotine
rs145157460	Metabolism/PK	3	nicotine
rs145308399	Metabolism/PK	3	nicotine
rs148693084	Metabolism/PK	3	nicotine
rs1801272	Other	3	coumarin
rs199515342	Metabolism/PK	3	nicotine
rs200554095	Metabolism/PK	3	nicotine
rs28399433	Other	3	nicotine
rs28399433	Other	3	coumarin
rs28399433	Other	3	tegafur
rs28399433	Toxicity	3	nicotine	Tobacco Use Disorder
rs28399433	Other	3	efavirenz	HIV infectious disease
rs28399454	Other	4	efavirenz	HIV infectious disease
rs28399468	Other	3	nicotine
rs374515279	Metabolism/PK	3	nicotine
rs376817657	Metabolism/PK	3	nicotine
rs4803381	Efficacy	3	bupropion;Drugs used in nicotine dependence	Tobacco Use Disorder
rs4803381	Metabolism/PK	3	nicotine
rs5031016	Metabolism/PK	3	nicotine
rs56113850	Metabolism/PK	3	nicotine	Tobacco Use Disorder
rs571335587	Metabolism/PK	3	nicotine
rs61605570	Metabolism/PK	3	nicotine
rs72549435	Metabolism/PK	3	nicotine
rs758479488	Metabolism/PK	3	nicotine
rs768416963	Metabolism/PK	3	nicotine
rs772964366	Metabolism/PK	3	nicotine

PharmGKB variants

78 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1137115	CYP2A6		0.00	0
rs1801272	CYP2A6	3	0.25	8	coumarin
rs1809810	CYP2A6		0.00	3
rs4803381	CYP2A6	3	1.75	2	nicotine;bupropion;Drugs used in nicotine dependence
rs4986891	CYP2A6		0.00	3
rs5031016	CYP2A6	3	0.12	6	nicotine
rs5031017	CYP2A6		0.00	1
rs6413474	CYP2A6		0.00	1
rs8192720	CYP2A6	3	1.00	1	tegafur
rs8192725	CYP2A6	3	0.12	1	tegafur
rs8192726	CYP2A6	4	-0.50	1	efavirenz
rs8192730	CYP2A6		0.00	2
rs12460590	CYP2A6, CYP2A7		0.00	0
rs28399433	CYP2A6	3	5.38	14	efavirenz;nicotine;coumarin;tegafur
rs28399434	CYP2A6		0.00	1
rs28399435	CYP2A6		0.00	1
rs28399445	CYP2A6		0.00	2
rs28399454	CYP2A6	4	-6.00	6	efavirenz
rs28399463	CYP2A6		0.00	2
rs28399468	CYP2A6	3	0.12	4	nicotine
rs56113850	CYP2A6	3	1.25	1	nicotine
rs56256500	CYP2A6		0.00	3
rs59552350	CYP2A6		0.00	2
rs60563539	CYP2A6		0.00	1
rs60605885	CYP2A6		0.00	1
rs72549435	CYP2A6	3	0.00	3	nicotine
rs140471703	CYP2A6		0.00	1
rs143690364	CYP2A6		0.00	1
rs143731390	CYP2A6		0.00	3
rs148166815	CYP2A6		0.00	1
rs376817657	CYP2A6	3	2.50	1	nicotine
rs28399447	CYP2A6		0.00	2
rs57837628	CYP2A6		0.00	0
rs7260629	CYP2A6		0.00	0
rs7259706	CYP2A6		0.00	0
rs28399453	CYP2A6		0.00	0
rs8192733	CYP2A6		0.00	0
rs145014075	CYP2A6	3	1.25	1	nicotine
rs571335587	CYP2A6	3	0.00	1	nicotine
rs768416963	CYP2A6	3	0.00	1	nicotine

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP2 family: drug metabolising subset

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 38a [PMID: 15634016]	Inhibition	7.7	pKi
compound 39a [PMID: 15634016]	Inhibition	7.4	pKi
esculetin	Inhibition	6.41	pIC50
compound 23 [PMID: 17125252]	Inhibition	6.22	pKi

Binding affinities (BindingDB)

23 measured of 146 human assays (147 total across all organisms); most potent 23 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-bromo-2-(1-methylpyrazol-4-yl)-7-[4-(pyridin-3-ylmethyl)piperazin-1-yl]-1H-imidazo[4,5-b]pyridine	IC50	32 nM	US-9447092: Pharmaceutically active compounds
6-chloro-7-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridine	IC50	38 nM	US-9447092: Pharmaceutically active compounds
3-[[4-[6-chloro-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-1,2,4-oxadiazole	IC50	40 nM	US-9447092: Pharmaceutically active compounds
3-[[4-[6-chloro-2-(1,3-dimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]piperazin-1-yl]methyl]-5-methyl-1,2,4-oxadiazole	IC50	52 nM	US-9447092: Pharmaceutically active compounds
(5-pyridin-3-ylthiophen-2-yl)methanamine	IC50	160 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
1-(4-Chlorobenzyl)-1H-imidazole	IC50	160 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
3-(3-methylthiophen-2-yl)pyridine	IC50	200 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
6-bromo-7-[4-(pyridin-3-ylmethyl)piperazin-1-yl]-2-(1,3,5-trimethylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridine	IC50	300 nM	US-9447092: Pharmaceutically active compounds
2-[1-({6-chloroimidazo[2,1-b][1,3]thiazole-5-}sulfonyl)-1H-indol-3-yl]ethan-1-amine	KI	458 nM
3-(5-methyl-1H-imidazol-1-yl)pyridine	KI	500 nM
3-pyridin-3-ylprop-2-yn-1-amine	IC50	514 nM	US-8609708: Synthetic compounds and derivatives as modulators of smoking or nicotine ingestion and lung cancer
(5-Phenylfuran-2-yl)methanamine	KI	600 nM
(5-Phenylthiophen-2-yl)methanamine	KI	600 nM
1-({[5-(pyridin-3-yl)furan-2-yl]methyl}sulfanyl)ethan-1-one	KI	800 nM
3-{5-[(methylsulfanyl)methyl]furan-2-yl}pyridine	KI	800 nM
3-Phenylthiophene	KI	3300 nM
4-methyl-2-(pyridin-3-yl)-1,3-thiazole	KI	4100 nM
Tranylcypromine,(+)	KI	5960 nM
3-Methyl-4-phenylthiophene	KI	6200 nM
3-(Pyridin-3-yl)propan-1-amine	KI	6600 nM
3-[5-(1,3-dithiolan-2-yl)furan-2-yl]pyridine	KI	13900 nM
1-Cyclohexylmethyl-1H-imidazole	IC50	170000 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration
1-(2-phenylethyl)imidazole	IC50	618000 nM	US-8906943: Synthetic compounds and methods to decrease nicotine self-administration

ChEMBL bioactivities

402 potent at pChembl≥5 of 530 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.24	Ki	0.057	nM	CHEMBL3740883
8.81	Ki	1.54	nM	CHEMBL3740902
8.76	Ki	1.73	nM	CHEMBL3741757
8.71	Ki	1.93	nM	CHEMBL3739596
8.59	Ki	2.58	nM	CHEMBL3742383
8.59	Ki	2.57	nM	CHEMBL3742224
8.57	Ki	2.7	nM	CHEMBL3741819
8.51	Ki	3.07	nM	CHEMBL3740871
8.48	Ki	3.27	nM	CHEMBL3740860
8.47	Ki	3.41	nM	CHEMBL3740335
8.22	Ki	6.02	nM	CHEMBL3742302
8.00	Ki	10	nM	CHEMBL1770735
8.00	Ki	10	nM	CHEMBL5289073
7.96	Ki	10.97	nM	CHEMBL3740529
7.89	Ki	12.96	nM	CHEMBL3739579
7.88	Ki	13.2	nM	CHEMBL3739672
7.78	Ki	16.62	nM	CHEMBL3740695
7.77	IC50	17	nM	CHEMBL4161819
7.70	Ki	20	nM	CHEMBL359657
7.70	IC50	20	nM	CHEMBL3640770
7.52	Ki	30	nM	CHEMBL450963
7.40	Ki	40	nM	CHEMBL178090
7.40	Ki	40	nM	CHEMBL360541
7.40	Ki	40	nM	CHEMBL149808
7.40	Ki	40	nM	CHEMBL180270
7.40	IC50	40	nM	CHEMBL5289073
7.38	IC50	42	nM	CHEMBL4165249
7.30	IC50	50	nM	CHEMBL3358215
7.30	IC50	50	nM	CHEMBL450963
7.30	Ki	50	nM	CHEMBL502746
7.30	IC50	50	nM	CHEMBL596015
7.29	IC50	51	nM	CHEMBL4173133
7.26	IC50	55	nM	CHEMBL4173088
7.22	Ki	60	nM	CHEMBL3358193
7.16	Ki	70	nM	CHEMBL3358223
7.16	Ki	70	nM	CHEMBL3358215
7.16	Ki	70	nM	CHEMBL3358192
7.12	IC50	76	nM	CHEMBL4160749
7.10	Ki	80	nM	CHEMBL359657
7.10	IC50	80	nM	TRANYLCYPROMINE
7.10	Ki	80	nM	CHEMBL448936
7.05	Ki	90	nM	CHEMBL360541
7.05	Ki	90	nM	CHEMBL3358194
7.05	Ki	90	nM	METHOXSALEN
7.00	Ki	100	nM	CHEMBL179669
7.00	Ki	100	nM	CHEMBL3358216
7.00	IC50	100	nM	CHEMBL1770735
7.00	Ki	100	nM	CHEMBL178090
6.96	IC50	110	nM	CHEMBL4169324
6.89	Ki	130	nM	CHEMBL360999

PubChem BioAssay actives

326 with measured affinity, of 1226 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
1-[4-(3-oxobenzo[f]chromen-2-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0001	uM
1-[4-(6-bromo-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-methylphenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0015	uM
1-[4-(6,8-dibromo-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-methylphenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0017	uM
1-[4-(8-methoxy-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-methylphenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0019	uM
1-[4-(6-chloro-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0026	uM
1-[4-(6,8-dichloro-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-methylphenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0026	uM
3-(4-chlorophenyl)-1-[4-(6,8-dichloro-2-oxochromen-3-yl)-1,3-thiazol-2-yl]pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0027	uM
1-[4-(6,8-dichloro-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0031	uM
3-(4-chlorophenyl)-1-[4-(8-methoxy-2-oxochromen-3-yl)-1,3-thiazol-2-yl]pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0033	uM
1-[4-(6,8-dibromo-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0034	uM
1-[4-(6-bromo-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0060	uM
5-prop-2-ynoxychromen-2-one	1951561: Competitive inhibition of CYP2A6 (unknown origin)	ki	0.0100	uM
1-benzothiophen-2-ylmethanamine	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.0100	uM
3-(4-methylphenyl)-1-[4-(2-oxochromen-3-yl)-1,3-thiazol-2-yl]pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0110	uM
1-[4-(2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-phenylpyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0130	uM
1-[4-(6-bromo-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-chlorophenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0132	uM
1-[4-(6-chloro-2-oxochromen-3-yl)-1,3-thiazol-2-yl]-3-(4-chlorophenyl)pyrazole-4-carbaldehyde	1265206: Inhibition of human microsomal CYP2A6	ki	0.0166	uM
[5-(4-ethyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0170	uM
(5-pyridin-3-ylthiophen-2-yl)methanamine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.0200	uM
5-prop-2-enoxychromen-2-one	1951561: Competitive inhibition of CYP2A6 (unknown origin)	ki	0.0300	uM
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline	2022035: Inhibition of CYP450 (unknown origin)	ic50	0.0335	uM
(5-pyridin-3-ylfuran-2-yl)methanamine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.0400	uM
[5-(4-propyl-3-pyridinyl)thiophen-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0420	uM
5-methoxychromen-2-one	1951560: Mixed type inhibition of CYP2A6 (unknown origin)	ki	0.0500	uM
1-benzothiophene-3-carbaldehyde	632144: Inhibition of CYP2A6 in human liver microsomes assessed as inhibition of coumarin 7-hydroxylation after 30 mins preincubation by plate reader	ic50	0.0500	uM
1-benzofuran-5-carbaldehyde	1174076: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate incubated for 30 mins prior to substrate addition measured after 10 mins by fluorescence assay	ic50	0.0500	uM
[5-(4-ethyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0510	uM
3-(4-methyl-3-pyridinyl)prop-2-yn-1-amine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0550	uM
thieno[2,3-c]pyridine-2-carbaldehyde	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.0600	uM
thieno[3,2-c]pyridine-2-carbaldehyde	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.0700	uM
1H-indole-5-carbaldehyde	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.0700	uM
[5-[4-(furan-3-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.0760	uM
5-ethoxychromen-2-one	1951561: Competitive inhibition of CYP2A6 (unknown origin)	ki	0.0800	uM
3-pyridin-3-ylprop-2-yn-1-amine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.0900	uM
(5-chloro-1-benzothiophen-3-yl)methanamine	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.0900	uM
methoxsalen	1951560: Mixed type inhibition of CYP2A6 (unknown origin)	ki	0.0900	uM
3-(3-methylthiophen-2-yl)pyridine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1000	uM
1-benzofuran-5-carbonitrile	1174075: Inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate preincubated for 10 mins by fluorescence assay	ki	0.1000	uM
[5-[4-(furan-3-yl)-3-pyridinyl]furan-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1100	uM
3-(1-methylimidazol-4-yl)pyridine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1300	uM
3-(4-phenyl-3-pyridinyl)prop-2-yn-1-amine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1300	uM
3-(3-methyl-1H-imidazol-3-ium-4-yl)pyridine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1300	uM
trans-(1S,2R)-2-phenylcyclopropan-1-amine;trans-(1R,2S)-2-phenylcyclopropan-1-amine	1209284: Mixed inhibition of CYP2A6 (unknown origin)	ki	0.1300	uM
1-benzothiophene-2-carbaldehyde	1174077: Irreversible inhibition of human CYP2A6 in baculovirus-infected insect cell system using coumarin 7 as substrate incubated for 10 mins by fluorescence assay	ki	0.1300	uM
[5-(4-propyl-3-pyridinyl)furan-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1400	uM
3-pyridin-3-ylprop-2-yn-1-amine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1600	uM
[5-[4-(furan-2-yl)-3-pyridinyl]thiophen-2-yl]methanamine;dihydrochloride	1356003: Inhibition of CYP2A6 in human liver microsomes using coumarin as substrate preincubated for 5 mins followed by addition of NADPH-regenerating system and measured after 15 mins by UPLC-MS analysis	ic50	0.1600	uM
3-(4-methylimidazol-1-yl)pyridine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1700	uM
3-methyl-5-(4-methylthiophen-3-yl)pyridine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1700	uM
N-methyl-1-(5-pyridin-3-ylthiophen-2-yl)methanamine	238615: Effect on coumarin 7-hydroxylation by human Cytochrome P-450 2A6	ki	0.1800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nicotine	increases expression, decreases reaction, decreases abundance, decreases metabolic processing, affects abundance (+8 more)	52
coumarin	decreases activity, decreases metabolic processing, affects binding, decreases reaction, increases glutathionylation (+5 more)	39
Cotinine	decreases abundance, affects chemical synthesis, affects metabolic processing, increases abundance, increases chemical synthesis (+2 more)	24
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases activity, increases reaction, affects metabolic processing, increases metabolic processing, increases hydroxylation	12
Tranylcypromine	decreases reaction, increases abundance, increases chemical synthesis, increases glutathionylation, increases metabolic processing (+4 more)	12
Methoxsalen	decreases activity, decreases reaction, increases chemical synthesis, increases metabolic processing	9
Rifampin	affects binding, increases reaction, increases expression, affects cotreatment	9
7-hydroxycoumarin	increases chemical synthesis, increases metabolic processing, decreases reaction	8
Phenobarbital	increases expression, increases activity, affects cotreatment	8
N’-nitrosonornicotine	affects metabolic processing, increases activity, increases hydroxylation, increases metabolic processing	5
Diethylnitrosamine	increases activity, increases reaction, affects metabolic processing, increases metabolic processing, affects localization (+1 more)	5
Tobacco Smoke Pollution	increases expression, affects activity, affects expression, decreases expression	5
hydroxycotinine	affects metabolic processing, increases chemical synthesis	4
1,7-dimethylxanthine	increases metabolic processing, increases chemical synthesis, affects metabolic processing, increases activity, increases hydroxylation	4
Acetaminophen	increases metabolic processing, affects cotreatment, decreases expression, increases expression	4
Tegafur	affects metabolic processing, increases activity, decreases activity, increases metabolic processing, increases response to substance	4
N-nitroso(di-n-propyl)amine	increases activity, increases reaction, affects metabolic processing	3
Benzo(a)pyrene	increases expression, increases reaction, decreases expression	3
DEET	increases metabolic processing, increases expression, affects cotreatment	3
Halothane	affects metabolic processing, increases metabolic processing	3
Methoxychlor	decreases methylation	3
N-Nitrosopyrrolidine	affects metabolic processing, increases activity, increases metabolic processing, decreases expression	3
Nitrosamines	increases metabolic processing, affects metabolic processing, increases activity	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Valproic Acid	increases metabolic processing, decreases methylation, increases expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases response to substance, affects expression	3
Fadrozole	affects metabolic processing, increases metabolic processing	3
N-nitrosopiperidine	affects metabolic processing, increases activity, increases metabolic processing	2
2,4,5,2’,5’-pentachlorobiphenyl	increases hydroxylation, increases metabolic processing	2
N’-nitrosoanabasine	affects metabolic processing, increases activity, increases metabolic processing	2

ChEMBL screening assays

414 unique, capped per target: 387 admet, 27 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

10 cell lines: 8 transformed cell line, 1 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5332	MCL-5	Transformed cell line	Male
CVCL_B5VX	Hepc/2A6L.14	Cancer cell line	Male
CVCL_F0FX	V79MZh2A6	Spontaneously immortalized cell line	Male
CVCL_F1MX	HyCyte BEAS-2B KO-hCYP2A6	Transformed cell line	Male
CVCL_IQ14	THLE-5B-2A6	Transformed cell line	Sex unspecified
CVCL_UG84	HEK293 CYP2A6*1A	Transformed cell line	Female
CVCL_UG85	HEK293 CYP2A6*1A-V5	Transformed cell line	Female
CVCL_UU63	MCL-1	Transformed cell line	Male
CVCL_UU64	MCL-2	Transformed cell line	Male
CVCL_WZ49	BEAS-2B/CYP2A6	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006170	PHASE4	COMPLETED	Bupropion and Weight Control for Smoking Cessation - 1
NCT00046813	PHASE4	TERMINATED	Nicotine Patch for Nicotine Dependence in Individuals With Schizophrenia or Schizoaffective Disorder - 1
NCT00061061	PHASE4	COMPLETED	Tobacco Cessation in Postmenopausal Women (Part I) - 1
NCT00119210	PHASE4	TERMINATED	Pilot Study of Bupropion for Smoking Cessation in Postpartum Non-breastfeeding Women
NCT00142831	PHASE4	COMPLETED	Bupropion as an Adjunct to the Nicotine Patch Plus CBT
NCT00176449	PHASE4	COMPLETED	A Comparison of Bupropion SR and Placebo for Smoking Cessation
NCT00178685	PHASE4	COMPLETED	Smokers’ Health Project: Self-Determination and Maintaining Tobacco Abstinence
NCT00186446	PHASE4	COMPLETED	Treatment of Nicotine Dependence and Acute Depression
NCT00307203	PHASE4	COMPLETED	Safety and Effectiveness of Sustained Release Bupropion in Treating Individuals With Schizophrenia Who Smoke
NCT00332644	PHASE4	COMPLETED	Smoking Cessation Medications: Efficacy, Mechanisms and Algorithms
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00484692	PHASE4	COMPLETED	Randomized Trial of Ultrashort Psychotherapy vs Sustained-Release Bupropion for Smoking Cessation
NCT00511134	PHASE4	TERMINATED	Study of Lunesta Versus Placebo for Sleep Problems Related to Smoking Cessation and Zyban
NCT00548470	PHASE4	COMPLETED	Varenicline Effects In Schizophrenic Smokers
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00727103	PHASE4	COMPLETED	Varenicline Treatment in Alcohol and Nicotine Dependent Patients With Schizophrenia
NCT00781755	PHASE4	WITHDRAWN	Treating Schizophrenic Smokers: Effects on Craving, Cues and Withdrawal
NCT00936299	PHASE4	COMPLETED	Bupropion for ADHD in Adolescents With Substance Use Disorder
NCT00948155	PHASE4	COMPLETED	Measuring Smoking Behaviors While Using Varenicline
NCT00948649	PHASE4	COMPLETED	Effects of Chantix on Relapse Prevention for Smoking Cessation
NCT01015170	PHASE4	COMPLETED	STOP Study: Effectiveness of Zyban in a Clinical Population
NCT01023659	PHASE4	COMPLETED	Distribution of Bupropion and Varenicline to Increase Smoking Cessation Attempts
NCT01047527	PHASE4	COMPLETED	An Effectiveness Trial of Maintenance Therapy for Nicotine Dependence
NCT01048944	PHASE4	COMPLETED	Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers
NCT01116986	PHASE4	COMPLETED	Identifying Optimal Smoking Cessation Intervention Components (Cessation)
NCT01120704	PHASE4	COMPLETED	Evaluation of Treatments to Improve Smoking Cessation Medication Adherence
NCT01122238	PHASE4	COMPLETED	Identifying Treatments to Motivate Smokers to Quit
NCT01342523	PHASE4	COMPLETED	Evaluation of National Cancer Institute (NCI) Smoking Intervention Resources
NCT01390246	PHASE4	COMPLETED	Bupropion for Smoking Cessation During Pregnancy
NCT01553084	PHASE4	COMPLETED	A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
NCT01554436	PHASE4	COMPLETED	Neuropsychological Prognosis Factors of Smoking Cessation
NCT01576640	PHASE4	TERMINATED	Extended Duration Nicotine Replacement Therapy and Bupropion in Smokers With Schizophrenia
NCT01656733	PHASE4	COMPLETED	Nicotine Replacement for Smoking Cessation During Pregnancy
NCT01664741	PHASE4	COMPLETED	Nicotine Dependence, Withdrawal and Replacement Therapy Assessed by PET Imaging
NCT01772641	PHASE4	TERMINATED	A Smoking Intervention Study Using Scheduled Gradual Reduction With Varenicline to Help With Cessation
NCT01783912	PHASE4	COMPLETED	Helping Those With Mental Illness Quit Smoking
NCT01925781	PHASE4	TERMINATED	e-Cigarettes Versus NRT Gum for Smoking Cessation
NCT01954966	PHASE4	COMPLETED	Progesterone and Brain Imaging Study
NCT01980550	PHASE4	COMPLETED	Association of Functional COMT Val108/Met Polymorphism With Smoking Cessation in Nicotine Replacement Therapy
NCT02108626	PHASE4	COMPLETED	Electronic Cigarettes in Daily Dependent Smokers