CYP2A13

Summary

CYP2A13 (cytochrome P450 family 2 subfamily A member 13, HGNC:2608) is a protein-coding gene on chromosome 19q13.2, encoding Cytochrome P450 2A13 (Q16696). Exhibits a coumarin 7-hydroxylase activity.

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. Although its endogenous substrate has not been determined, it is known to metabolize 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a major nitrosamine specific to tobacco. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q.

Source: NCBI Gene 1553 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 92 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2608
Approved symbol	CYP2A13
Name	cytochrome P450 family 2 subfamily A member 13
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CPAD, CYP2A
Ensembl gene	ENSG00000197838
Ensembl biotype	protein_coding
OMIM	608055
Entrez	1553

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000330436, ENST00000874269

RefSeq mRNA: 1 — MANE Select: NM_000766 NM_000766

CCDS: CCDS12571

Canonical transcript exons

ENST00000330436 — 9 exons

Exon	Start	End
ENSE00001385067	41095760	41096195
ENSE00002437768	41094959	41095100
ENSE00002485162	41090404	41090564
ENSE00002499709	41088929	41089091
ENSE00002510522	41093630	41093771
ENSE00002512004	41091732	41091908
ENSE00002521943	41094245	41094432
ENSE00002536556	41090047	41090196
ENSE00003043328	41088451	41088651

Expression profiles

Bgee: expression breadth broad, 33 present calls, max score 93.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1015 / max 80.3735, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
208818	0.1015	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	93.71	gold quality
diaphragm	UBERON:0001103	93.10	gold quality
type B pancreatic cell	CL:0000169	92.85	gold quality
olfactory bulb	UBERON:0002264	92.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.33	gold quality
nasal cavity mucosa	UBERON:0001826	87.69	gold quality
Brodmann (1909) area 10	UBERON:0013541	86.54	gold quality
quadriceps femoris	UBERON:0001377	83.61	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.60	gold quality
gluteal muscle	UBERON:0002000	82.50	gold quality
heart right ventricle	UBERON:0002080	82.45	gold quality
triceps brachii	UBERON:0001509	81.95	gold quality
tongue squamous epithelium	UBERON:0006919	81.26	gold quality
hair follicle	UBERON:0002073	81.14	gold quality
paraflocculus	UBERON:0005351	80.95	silver quality
mucosa of paranasal sinus	UBERON:0005030	80.89	silver quality
middle frontal gyrus	UBERON:0002702	79.99	gold quality
frontal pole	UBERON:0002795	79.46	silver quality
biceps brachii	UBERON:0001507	79.22	gold quality
epithelium of bronchus	UBERON:0002031	79.04	silver quality
bronchus	UBERON:0002185	78.72	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	78.62	gold quality
thymus	UBERON:0002370	78.27	gold quality
upper arm skin	UBERON:0004263	77.36	gold quality
vena cava	UBERON:0004087	76.16	gold quality
bronchial epithelial cell	CL:0002328	76.11	silver quality
CA1 field of hippocampus	UBERON:0003881	75.32	gold quality
epithelial cell of pancreas	CL:0000083	75.23	gold quality
mucosa of urinary bladder	UBERON:0001259	73.75	gold quality
secondary oocyte	CL:0000655	73.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AIRE, CEBPD, CEBPG, DBP, FOXA2, HNF4A, IRF6, NFIC, NFKB, NFKBID, USF1

miRNA regulators (miRDB)

5 targeting CYP2A13, 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-4761-5P	99.51	66.69	804
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-558	97.50	67.16	977
HSA-MIR-1225-3P	97.29	64.60	876

Literature-anchored findings (GeneRIF, showing 37)

• genetic polymorphism: identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant (PMID:12130698)
• CYP2A13 allele is associated with reduced risk of lung adenocarcinoma, suggesting the role of NNK-CYP2A13 interaction as a causative factor for the cancer. (PMID:14633739)
• In order to investigate the extent of CYP2A13 genetic polymorphism in a French Caucasian population of 102 individuals, a screening for sequence variations in the 5’-untranslated and protein encoding regions of its gene was performed. (PMID:15063809)
• The CYP2A13 Arg257Cys variant represents a common polymorphism in Chinese, with the 257Cys allele frequency being similar to the Hispanic and Asian groups, but significantly lower than in blacks (PMID:15115698)
• CYP2A13 mutant proteins showed a significant decrease in the catalytic efficiency for NNK alpha-hydroxylation (PMID:15333516)
• structure of CYP2A13 was determined to 2.35A by x-ray crystallography and compared with structures of CYP2A6. (PMID:17428784)
• the reported association of the CYP2A13(*)2 allele with decreased incidences of lung adenocarcinoma in smokers can be at least partly explained by a decrease in CYP2A13 function (PMID:18669584)
• Observed clear prevalence of the variant CYP2A13 alelle causing premature stop at codon 101 (knockout allele *7) among the controls in comparison with the pancreatic cancer patients. (PMID:19812523)
• The mechanisms underlying the decreased allelic expression of a common CYP2A13 allele (7520C>G) in the human lung, were investigated. (PMID:20431511)
• 2 novel polymorphisms T478C and T494C in CYP2A13 gene were associated with significantly reduced risk of cancer. CYP2A13 haplotype carrying variant alleles of T478C/T494C found associated with reduced risk of head/neck cancer. (PMID:20534012)
• single nucleotide polymorphisms within the CYP2A13 gene affect metabolism of 5-methoxypsoralen in humans. (PMID:20798279)
• significant interaction between smoking and methylation status of CYP2A13 in head and neck cancer. (PMID:20846153)
• present results provide the first direct in vitro evidence demonstrating the predominant roles of CYP2A13 in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mutagenesis, possibly via metabolic activation of NNK alpha-hydroxylation (PMID:21473878)
• The distribution frequencies of all eight known CYP2A13 missense alleles were examined in a Chinese Han population. (PMID:22315333)
• Tissue distribution of transgenic mRNA expression agrees well with the known respiratory tract-selective expression of CYP2A13 and CYP2F1 and hepatic expression of CYP2B6 in humans. (PMID:22397853)
• Report CYP2A-selective inhibitors to accurately distinguish between CYP2A6 and CYP2A13 activity. (PMID:22696418)
• Although both the hepatic CYP2A6 and respiratory CYP2A13 enzymes metabolize these compounds, CYP2A13 does so with much higher catalytic efficiency, but the structural basis for this has been unclear (PMID:22700965)
• Report selective expression of CYP2A13 in human pancreatic alpha-islet cells. (PMID:22798551)
• The differential distribution pattern of CYP2A13 in the respiratory tract, which is of importance in considering the pulmonary susceptibility to carcinogens and the following lung cancer development, is detailed. (PMID:22890016)
• an efficient approach for expressing functionally characterized, highly active and homogeneous CYP2A13 proteins. (PMID:23463547)
• CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in the human respiratory system. (PMID:23583631)
• Findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. (PMID:23602888)
• Findings suggest the potential involvement of pulmonary CYP2A13 in the early occurrence of NSCLC as well as in the development of EGFR gene mutations. (PMID:23752126)
• Data suggest important role of CYP2A13 in AFG1- (aflatoxin G1)-induced cytotoxicity, DNA damage, and activation of signal pathways in bronchial epithelium; data suggest similarities in CYP2A13-catalyzed bioactivation of AFG1 and AFB1 (aflatoxin B1). (PMID:23907605)
• CYP2A13 is efficient in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation in vivo and it can mediate 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis. (PMID:23917075)
• CYP2A13 played a critical role in AFB1-induced neoplastic transformation. (PMID:24114584)
• The transgenic CYP2A13 is active. (PMID:24907355)
• an etiologically relevant interaction between CYP2A13 and ABCB1 associated with lung cancer was analysed (PMID:25667220)
• CYP2A13 levels in human lungs can be suppressed by disease-associated inflammation in tissue donors. (PMID:25710941)
• CYP2A13 is the most efficient enzyme to metabolize N’-Nitrosonornicotine in vitro. (PMID:27567546)
• The results of this case-control study suggested that the CYP2A13*1/*2 genotype decreased the risk of susceptibility to bladder cancer in Japanese smokers (PMID:27725446)
• Oxidation of 1-chloropyrene by human CYP1 family and CYP2A subfamily cytochrome P450 enzymes: catalytic roles of two CYP1B1 and five CYP2A13 allelic variants (PMID:28648140)
• Functional analysis of variations in P450 2A13 allelic variants may help to understand the consequences of P450 2A13 polymorphism in bioactivation of many tobacco-derived carcinogens. (PMID:29652224)
• Study provides evidence that CYP2A13 gene polymorphisms may be candidate biomarkers of lung cancer susceptibility in Chinese. (PMID:30807688)
• Association between CYP2A13 polymorphisms and lung cancer: A protocol for systematic review and meta-analysis. (PMID:33327254)
• Molecular docking and oxidation kinetics of 3-phenyl coumarin derivatives by human CYP2A13. (PMID:33703988)
• Genetic and Enzymatic Characteristics of CYP2A13 in Relation to Lung Damage. (PMID:34830188)

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), CYP2A7 (ENSG00000198077), CYP2A6 (ENSG00000255974)

Protein

Protein identifiers

Cytochrome P450 2A13 — Q16696 (reviewed: Q16696)

Alternative names: CYPIIA13

All UniProt accessions (1): Q16696

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2’-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Expressed in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle.

Polymorphism. The frequencies of the Cys-257 allele in white, black, Hispanic, and Asian individuals are 1.9%, 14.4%, 5.8%, and 7.7%, respectively. The Cys-257 variant is 37 to 56% less active than the wild-type Arg-257 protein toward all substrates tested.

Similarity. Belongs to the cytochrome P450 family.

RefSeq proteins (1): NP_000757* (*=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

Catalyzed reactions (Rhea), 1 shown:

• an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)

UniProt features (64 total): helix 20, strand 11, mutagenesis site 10, sequence variant 8, turn 7, sequence conflict 5, binding site 2, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2PG5	X-RAY DIFFRACTION	1.95
4EJI	X-RAY DIFFRACTION	2.1
2P85	X-RAY DIFFRACTION	2.35
4EJH	X-RAY DIFFRACTION	2.35
4EJG	X-RAY DIFFRACTION	2.5
2PG6	X-RAY DIFFRACTION	2.53
2PG7	X-RAY DIFFRACTION	2.8
3T3S	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16696-F1	96.27	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 (2): 297; 439 (axial binding residue)

Mutagenesis-validated functional residues (10):

Position	Phenotype
110	decreases phenacetin o-deethylation activity 8 fold.
117	increases phenacetin o-deethylation activity 5 fold.
208	decreases phenacetin o-deethylation activity 10 fold.
213	decreases phenacetin o-deethylation activity 2 fold.
300	decreases phenacetin o-deethylation activity 40 fold.
301	decreases phenacetin o-deethylation activity 20 fold.
365	decreases phenacetin o-deethylation activity 7 fold.
366	increases phenacetin o-deethylation activity 3 fold.
369	decreases phenacetin o-deethylation activity 9 fold.
372	decreases phenacetin o-deethylation activity 3 fold.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-211935	Fatty acids
R-HSA-211981	Xenobiotics
R-HSA-211999	CYP2E1 reactions
R-HSA-5423646	Aflatoxin activation and detoxification

MSigDB gene sets: 66 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, BENPORATH_ES_WITH_H3K27ME3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, MAHAJAN_RESPONSE_TO_IL1A_DN, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_TOXIN_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_UNSATURATED_FATTY_ACID_METABOLIC_PROCESS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_OK_VS_DONOR_DN, GOBP_ARACHIDONATE_METABOLIC_PROCESS, GOBP_EPOXYGENASE_P450_PATHWAY, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (4): xenobiotic metabolic process (GO:0006805), coumarin metabolic process (GO:0009804), epoxygenase P450 pathway (GO:0019373), aflatoxin metabolic process (GO:0046222)

GO Molecular Function (9): monooxygenase activity (GO:0004497), 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), heme binding (GO:0020037), 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 (4): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	2
Xenobiotics	1
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity	2
monooxygenase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
cellular anatomical structure	2
metabolic process	1
cellular response to xenobiotic stimulus	1
phenylpropanoid metabolic process	1
arachidonate metabolic process	1
mycotoxin metabolic process	1
transition metal ion binding	1
arachidonate monooxygenase activity	1
tetrapyrrole 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
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP2A13	PPIG	Q13427	895
CYP2A13	APOC2	P02655	730
CYP2A13	NR1I2	O75469	632
CYP2A13	CYB5B	O43169	593
CYP2A13	CYB5A	P00167	593
CYP2A13	CEACAM7	Q14002	544
CYP2A13	PEPD	P12955	526
CYP2A13	GPI	P06744	522
CYP2A13	CEACAM4	O75871	521
CYP2A13	CKM	P06732	506
CYP2A13	RYR1	P21817	467
CYP2A13	CEACAM3	P40198	459
CYP2A13	APOC1	P02654	451
CYP2A13	NR1I3	Q14994	441
CYP2A13	PIGQ	Q9BRB3	436

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CYP2A7	CYP2A6	psi-mi:“MI:0914”(association)	0.350
CYP2A13	CD63	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): CYP2A13 (Affinity Capture-MS), TIMM10 (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), CD63 (Affinity Capture-MS), EBNA1BP2 (Cross-Linking-MS (XL-MS))

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: A0A087X1C5, E9Q5K4, F1Q8C3, O18809, O18992, O35293, O46658, O54749, O54750, O55071, O62671, O93297, P00176, P00178, P00179, P00180, P00181, P00182, P04167, P05178, P05179, P05180, P05181, P08682, P08683, P10610, P10632, P10633, P10634, P10635, P11371, P11712, P11714, P12789, P12790, P12791, P12938, P12939, P15123, P17666

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

940 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41088630:GAT:G	donor_gain	1.0000
19:41088648:G:GT	donor_gain	1.0000
19:41088649:A:T	donor_gain	1.0000
19:41088928:GATCA:G	acceptor_gain	1.0000
19:41089086:GC:G	donor_gain	1.0000
19:41089087:C:G	donor_gain	1.0000
19:41089089:ATGGT:A	donor_loss	1.0000
19:41089093:T:A	donor_loss	1.0000
19:41089097:G:GT	donor_gain	1.0000
19:41090032:C:CA	acceptor_gain	1.0000
19:41090037:A:AG	acceptor_gain	1.0000
19:41090038:C:G	acceptor_gain	1.0000
19:41090042:CCCA:C	acceptor_loss	1.0000
19:41090045:A:AG	acceptor_gain	1.0000
19:41090045:AG:A	acceptor_gain	1.0000
19:41090045:AGGC:A	acceptor_gain	1.0000
19:41090046:G:GG	acceptor_gain	1.0000
19:41090046:GG:G	acceptor_gain	1.0000
19:41090046:GGC:G	acceptor_gain	1.0000
19:41090046:GGCG:G	acceptor_gain	1.0000
19:41090046:GGCGT:G	acceptor_gain	1.0000
19:41090192:GCACG:G	donor_gain	1.0000
19:41090193:CACG:C	donor_gain	1.0000
19:41090194:ACG:A	donor_gain	1.0000
19:41090195:CG:C	donor_gain	1.0000
19:41090196:GG:G	donor_gain	1.0000
19:41090197:G:GA	donor_loss	1.0000
19:41090197:G:GG	donor_gain	1.0000
19:41090397:C:G	acceptor_gain	1.0000
19:41091721:T:TA	acceptor_gain	1.0000

AlphaMissense

3282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41095091:T:C	F432L	0.993
19:41095093:T:A	F432L	0.993
19:41095093:T:G	F432L	0.993
19:41095043:T:C	F416L	0.986
19:41095045:C:A	F416L	0.986
19:41095045:C:G	F416L	0.986
19:41093717:A:C	S307R	0.985
19:41093719:C:A	S307R	0.985
19:41093719:C:G	S307R	0.985
19:41094331:G:C	A354P	0.982
19:41094344:A:T	E358V	0.981
19:41093654:T:C	F286L	0.978
19:41093656:C:A	F286L	0.978
19:41093656:C:G	F286L	0.978
19:41095028:T:C	F411L	0.978
19:41095030:C:A	F411L	0.978
19:41095030:C:G	F411L	0.978
19:41088606:C:A	N45K	0.976
19:41088606:C:G	N45K	0.976
19:41093730:G:C	R311P	0.976
19:41094354:A:C	R361S	0.976
19:41094354:A:T	R361S	0.976
19:41095760:G:A	G435E	0.975
19:41093727:T:C	L310P	0.974
19:41095029:T:C	F411S	0.974
19:41089008:T:A	V87D	0.973
19:41089040:T:C	F98L	0.973
19:41089042:C:A	F98L	0.973
19:41089042:C:G	F98L	0.973
19:41090457:A:C	S183R	0.973

dbSNP variants (sampled 300 via entrez): RS1000381655 (19:41092180 G>A), RS1000445929 (19:41087534 G>A), RS1000622862 (19:41087872 T>C), RS1000880106 (19:41087351 G>A), RS1001156770 (19:41088754 G>A), RS1001382572 (19:41092203 C>A), RS1002129003 (19:41088176 T>A,C), RS1003393647 (19:41094843 C>T), RS1004182564 (19:41089482 C>T), RS1004276385 (19:41089763 C>A,G,T), RS1004705578 (19:41095407 G>A,C), RS1004718486 (19:41090298 G>A), RS1005246973 (19:41095688 C>CG), RS1005403263 (19:41086855 CA>C), RS1006163229 (19:41091504 A>T)

Disease associations

OMIM: gene MIM:608055 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003629_12	Nicotine metabolite ratio in current smokers	2.000000e-08
GCST010867_48	Coronary artery disease	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007794	nicotine metabolite ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3542436 (SINGLE PROTEIN), CHEMBL4523986 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 257,435 (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
CHEMBL3	NICOTINE	4	184,969
CHEMBL3989843	TRANYLCYPROMINE	4	70
CHEMBL416	METHOXSALEN	4	19,665
CHEMBL550	PILOCARPINE	4	37,191
CHEMBL477772	PAZOPANIB	4	15,540

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1709083	Toxicity	3	nicotine	Tobacco Use Disorder
rs72552266	Toxicity	3	nicotine	Tobacco Use Disorder

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8192789	CYP2A13		0.00	0
rs72552266	CYP2A13	3	2.50	1	nicotine
rs148044792	CYP2A13		0.00	0
rs1709083	CYP2A13	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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
kaempferol	Inhibition	6.92	pKi

ChEMBL bioactivities

34 potent at pChembl≥5 of 46 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	Ki	40	nM	METHOXSALEN
6.60	IC50	251.2	nM	CHEMBL601428
6.37	Kd	430	nM	PHENETHYLISOTHIOCYANATE
6.24	Kd	580	nM	CHEMBL3526658
6.19	Kd	650	nM	CHEMBL3188333
6.16	IC50	700	nM	CHEMBL3330409
6.05	IC50	900	nM	CHEMBL3330410
5.96	IC50	1100	nM	CHEMBL2130955
5.85	Ki	1400	nM	PILOCARPINE
5.80	Kd	1600	nM	METHOXSALEN
5.72	Kd	1900	nM	CHEMBL4437617
5.72	IC50	1900	nM	CHEMBL2130955
5.64	Kd	2300	nM	TRANYLCYPROMINE
5.60	IC50	2500	nM	CHEMBL5612347
5.55	IC50	2800	nM	CHEMBL2130955
5.52	Kd	3000	nM	PILOCARPINE
5.43	IC50	3700	nM	CHEMBL5406721
5.43	IC50	3700	nM	CHEMBL46909
5.42	Ki	3800	nM	PHENETHYLISOTHIOCYANATE
5.42	IC50	3800	nM	CHEMBL5418617
5.41	IC50	3900	nM	CHEMBL5429178
5.31	IC50	4900	nM	CHEMBL2130955
5.28	Kd	5200	nM	TRYPTAMINE
5.25	Ki	5600	nM	NICOTYRINE
5.24	Kd	5800	nM	CHEMBL4575324
5.23	IC50	5900	nM	CHEMBL5406218
5.22	IC50	6053	nM	CHEMBL65590
5.19	Ki	6500	nM	TRANYLCYPROMINE
5.16	Kd	7000	nM	CHEMBL4452645
5.14	Kd	7300	nM	CHEMBL2262739
5.10	IC50	7900	nM	PAZOPANIB
5.09	Kd	8200	nM	NICOTYRINE
5.00	Kd	1e+04	nM	CHEMBL1479903
5.00	IC50	1e+04	nM	CHEMBL5395150

PubChem BioAssay actives

41 with measured affinity, of 518 total; 32 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
methoxsalen	1209283: Mixed inhibition of CYP2A13 (unknown origin)	ki	0.0400	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
2-isothiocyanatoethylbenzene	1209287: Binding affinity to CYP2A13 (unknown origin) assessed as type 1 interaction as increase in absorbance 379 to 387 nm and decrease in 414 to 420 nm	kd	0.4300	uM
(6R)-3,6-dimethyl-4,5,6,7-tetrahydro-1-benzofuran	1209287: Binding affinity to CYP2A13 (unknown origin) assessed as type 1 interaction as increase in absorbance 379 to 387 nm and decrease in 414 to 420 nm	kd	0.5800	uM
4-(dimethylamino)benzaldehyde	1209287: Binding affinity to CYP2A13 (unknown origin) assessed as type 1 interaction as increase in absorbance 379 to 387 nm and decrease in 414 to 420 nm	kd	0.6500	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
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
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
Pilocarpine	1209281: Competitive inhibition of CYP2A13 (unknown origin)	ki	1.4000	uM
1-hexylimidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	2.1000	uM
trans-(1S,2R)-2-phenylcyclopropan-1-amine;trans-(1R,2S)-2-phenylcyclopropan-1-amine	1209286: Binding affinity to CYP2A13 (unknown origin) assessed as type 2 interaction as increase in absorbance 431 to 432 nm and decrease in 406 to 412 nm	kd	2.3000	uM
1-hex-5-enylimidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	2.4000	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
1-heptylimidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	3.1000	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
1-pentylimidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	4.3000	uM
2-(1H-indol-3-yl)ethanamine	1209286: Binding affinity to CYP2A13 (unknown origin) assessed as type 2 interaction as increase in absorbance 431 to 432 nm and decrease in 406 to 412 nm	kd	5.2000	uM
1-[(E)-hex-3-enyl]imidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	5.5000	uM
3-(1-methylpyrrol-2-yl)pyridine	1209283: Mixed inhibition of CYP2A13 (unknown origin)	ki	5.6000	uM
1-(3-methylbutyl)imidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	5.6000	uM
1-(3-methylbut-2-enyl)imidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	5.7000	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
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
1-[(2Z)-3,7-dimethylocta-2,6-dienyl]imidazole	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	6.5000	uM
(5R)-3-[1-(1H-indol-2-ylmethyl)piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	7.9433	uM
2-hept-6-enylpyrazine	1799628: Inhibition Assay from Article 10.1002/cbic.200800712: “Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.”	ic50	9.8000	uM
3-[1-[(3,4-dimethylphenyl)methyl]piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one	306257: Inhibition of CYP450	ic50	10.0000	uM
1-[3-(3,5-dimethoxyphenyl)phenyl]-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	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases hydroxylation, increases response to substance, increases abundance, increases activity, decreases metabolic processing (+6 more)	11
Methoxsalen	increases activity, increases response to substance, decreases activity, decreases response to substance, decreases reaction (+1 more)	4
Tobacco Smoke Pollution	decreases expression, increases expression	4
Aflatoxin B1	decreases methylation, affects cotreatment, decreases expression, increases phosphorylation, increases cleavage (+6 more)	4
quinomethionate	affects expression, increases expression	2
N’-nitrosonornicotine	increases hydroxylation, increases metabolic processing, increases abundance, decreases reaction	2
sodium arsenite	decreases expression, increases expression	2
aflatoxin G1	increases expression, affects response to substance, increases activity	2
naphthalene	increases abundance, affects reaction, affects cotreatment, affects binding, increases metabolic processing (+1 more)	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nicotine	increases metabolic processing, decreases reaction, increases abundance, increases response to substance, decreases activity	2
Skatole	increases activity, increases metabolic processing, increases chemical synthesis, decreases activity, decreases response to substance	2
helenalin	increases oxidation, decreases activity	1
methyleugenol	decreases expression	1
4-biphenylamine	increases hydroxylation, increases activity	1
senecionine	increases expression	1
N’-nitrosoanabasine	decreases reaction, increases abundance, increases metabolic processing, decreases activity	1
biphenyl	affects binding, increases oxidation	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
N-methyl-N-nitrosoaniline	decreases reaction, increases metabolic processing	1
N,N-dimethylaniline	decreases reaction, increases metabolic processing	1
pyrrolidine dithiocarbamic acid	decreases expression, decreases reaction	1
acenaphthene-1-ol	increases oxidation, increases chemical synthesis	1
1-naphthol	increases abundance, increases oxidation	1
coumarin	decreases hydroxylation, increases hydroxylation	1
phenanthrene	increases oxidation, increases abundance, affects binding	1
N’-nitrosoanatabine	decreases reaction, increases abundance, increases metabolic processing, decreases activity	1
N-nitrosoguvacoline	increases activity	1
acenaphthene	increases oxidation, increases chemical synthesis	1
acenaphthylene	increases oxidation	1

ChEMBL screening assays

190 unique, capped per target: 187 admet, 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1743536	ADMET	Mechanism based inhibition of human cytochrome P450 2A13 measured by coumarin 7-hydroxylation and testosterone 15-hydroxylation	Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. — Curr Drug Metab
CHEMBL4418424	Binding	Binding affinity to full length recombinant truncated non-catalytic N-terminal transmembrane helix containing C-terminal 4xHis tagged human CYP2A13dH expressed in Escherichia coli by HTS assay	Morpholines as selective inhibitors of cytochrome P450 2A13

Cellosaurus cell lines

3 cell lines: 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_UG86	HEK293 CYP2A13*1A	Transformed cell line	Female
CVCL_UG87	HEK293 CYP2A13*1A-V5	Transformed cell line	Female
CVCL_WZ48	BEAS-2B/CYP2A13	Transformed cell line	Male

Clinical trials (associated diseases)

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