CYP2A6

cytochrome P450 family 2 subfamily A member 6, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 19:40843540-40850447

Previous symbols: [ "CYP2A3" ]

Links

ENSG00000255974 ∙ NCBI:1548 ∙ OMIM:122720 ∙ HGNC:2610 ∙ Uniprot:P11509 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• coumarin resistance (No Known Disease Relationship), mode of inheritance: Unknown
• nicotine dependence (No Known Disease Relationship), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CYP2A6-related drug metabolism	AD	Pharmacogenomic	Selection and dosing of medications may be affected by the presence of variants	General	2322567; 9409631; 9827545; 10093988; 12042667; 12325023; 19238117; 23089672

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2A6 gene.

• Inborn genetic diseases (15 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2A6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	2	5
missense			15	2	2	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	5	4

Variants in CYP2A6

This is a list of pathogenic ClinVar variants found in the CYP2A6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-40843841-A-G			Benign (Jul 18, 2018)
19-40843861-A-G		not specified	Uncertain significance (Aug 22, 2022)
19-40843897-G-A		not specified	Likely benign (Oct 27, 2023)
19-40844682-T-C			Benign (Dec 31, 2019)
19-40844695-G-A			Benign (Jul 31, 2018)
19-40844725-A-G			Likely benign (Feb 01, 2024)
19-40845309-A-C		not specified	Uncertain significance (Jul 05, 2022)
19-40845383-C-T		not specified	Uncertain significance (May 24, 2023)
19-40845449-C-T		not specified	Uncertain significance (Oct 24, 2023)
19-40845476-C-T		not specified	Likely benign (Dec 27, 2023)
19-40846030-A-G		not specified	Uncertain significance (Sep 15, 2021)
19-40846051-A-G		not specified	Uncertain significance (Sep 20, 2023)
19-40846092-C-T			Likely benign (Feb 14, 2018)
19-40846879-T-G		not specified	Uncertain significance (Feb 08, 2023)
19-40846886-G-A		not specified	Uncertain significance (Aug 13, 2021)
19-40846913-G-C		not specified	Uncertain significance (Oct 27, 2022)
19-40846953-C-A		not specified	Uncertain significance (Jul 05, 2023)
19-40846979-C-T		not specified	Uncertain significance (Oct 05, 2021)
19-40847036-A-G		Tegafur response	drug response (Jun 01, 2002)
19-40848238-G-A		not specified	Uncertain significance (Sep 26, 2022)
19-40848304-C-A			Likely benign (Apr 10, 2018)
19-40848334-T-C		not specified	Uncertain significance (May 17, 2023)
19-40848628-A-T		Warfarin response • Nicotine, poor metabolism of	drug response (Sep 01, 2000)
19-40848635-C-A		not specified	Uncertain significance (Jun 07, 2023)
19-40848643-A-C		not specified	Uncertain significance (May 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2A6	protein_coding	protein_coding	ENST00000301141	9	6910

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.40e-9	0.401	125122	12	466	125600	0.00190

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.53	375	300	1.25	0.0000173	3241
Missense in Polyphen		123	108.4	1.1346		1182
Synonymous	-3.39	162	116	1.40	0.00000659	940
Loss of Function	0.894	15	19.2	0.780	9.01e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0249	0.0243
Ashkenazi Jewish	0.000695	0.000695
East Asian	0.00127	0.00127
Finnish	0.00	0.00
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.00127	0.00127
South Asian	0.000229	0.000229
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:16086027, ECO:0000269|PubMed:17125252, ECO:0000269|PubMed:18779312, ECO:0000269|PubMed:1889415, ECO:0000269|PubMed:1944238}.
• Pathway: Artemisinin and Derivatives Pathway, Pharmacokinetics;Retinol metabolism - Homo sapiens (human);nicotine degradation III;Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Caffeine metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Fluoropyrimidine Pathway, Pharmacokinetics;Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Caffeine Pathway, Pharmacokinetics;Valproic Acid Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Nicotine Pathway, Pharmacokinetics;Cyclophosphamide Pathway, Pharmacokinetics;Ifosfamide Pathway, Pharmacokinetics;Nicotine Metabolism Pathway;Nicotine Action Pathway;Valproic Acid Metabolism Pathway;Cyclophosphamide Action Pathway;Ifosfamide Action Pathway;Acetaminophen Metabolism Pathway;Vitamin A Deficiency;Caffeine Metabolism;Cyclophosphamide Metabolism Pathway;Ifosfamide Metabolism Pathway;Retinol Metabolism;Nicotine Metabolism;Fluoropyrimidine Activity;Fatty Acid Omega Oxidation;Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Caffeine and Theobromine metabolism;Valproic acid pathway;Liver steatosis AOP;Oxidation by Cytochrome P450;Tamoxifen metabolism;Phase I - Functionalization of compounds;bupropion degradation;acetone degradation I (to methylglyoxal);Xenobiotics;Tyrosine metabolism;Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;superpathway of tryptophan utilization;CYP2E1 reactions;melatonin degradation I;superpathway of melatonin degradation;estradiol biosynthesis II;estradiol biosynthesis I;Arachidonic acid metabolism;superpathway of steroid hormone biosynthesis;nicotine degradation IV (Consensus)

Recessive Scores

• pRec: 0.521

Intolerance Scores

• loftool: 0.916
• rvis_EVS: 0.3
• rvis_percentile_EVS: 71.64

Haploinsufficiency Scores

• pHI: 0.232
• hipred: N
• hipred_score: 0.139

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.830

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp2a5
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;coumarin metabolic process;drug metabolic process;epoxygenase P450 pathway;exogenous drug catabolic process;coumarin catabolic process;oxidation-reduction process
• Cellular component: cytoplasm;endoplasmic reticulum membrane;cytoplasmic microtubule;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: iron ion binding;coumarin 7-hydroxylase activity;arachidonic acid epoxygenase activity;steroid hydroxylase activity;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;enzyme binding;heme binding