CYP1A2

cytochrome P450 family 1 subfamily A member 2, the group of Cytochrome P450 family 1

Basic information

Region (hg38): 15:74748844-74756607

Links

ENSG00000140505 ∙ NCBI:1544 ∙ OMIM:124060 ∙ HGNC:2596 ∙ Uniprot:P05177 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
CYP1A2-related drug metabolism	AD	Pharmacogenomic	Variants may also be related to subclinical metabolism of a number of agents (including medications), as well as related as a susceptibility factor; Porphyria cutanea tarda, severity of refersto a susceptibility locus and/or evidence or clinical applicability unclear	General	8035341; 10101295; 10233211; 10376760; 11153915; 12172216; 16522833; 17971810; 20881513; 20955109; 20147896; 19636338; 21121774; 19682433; 21989077

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP1A2 gene.

• Inborn genetic diseases (14 variants)
• not provided (6 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP1A2 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				2	1	3
missense			13	2	1	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	1	2
Total	0	0	13	5	3

Variants in CYP1A2

This is a list of pathogenic ClinVar variants found in the CYP1A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-74749576-C-A		not specified	Likely benign (Mar 09, 2018)
15-74749760-C-T		not specified	Uncertain significance (Jun 30, 2022)
15-74749880-T-G		not specified	Uncertain significance (Jul 06, 2021)
15-74749942-G-A		not specified	Uncertain significance (Aug 29, 2022)
15-74749958-G-A		not specified	Uncertain significance (Feb 16, 2023)
15-74750016-C-T		not specified	Uncertain significance (Jan 23, 2024)
15-74750044-C-T			Likely benign (Jun 28, 2018)
15-74750131-G-A			Likely benign (Jun 13, 2018)
15-74750139-C-T		not specified	Uncertain significance (Apr 18, 2023)
15-74750297-G-A		not specified	Likely benign (Jan 26, 2022)
15-74750381-G-A		not specified	Uncertain significance (Jun 21, 2022)
15-74750426-G-C		not specified	Uncertain significance (Dec 21, 2022)
15-74750516-T-C		not specified	Uncertain significance (Dec 21, 2022)
15-74751198-C-T			Likely benign (Aug 10, 2018)
15-74751226-A-G		not specified	Uncertain significance (Jun 07, 2023)
15-74751253-G-T		not specified	Uncertain significance (Nov 09, 2023)
15-74751805-G-A		not specified	Uncertain significance (Mar 01, 2024)
15-74752235-C-A		not specified	Uncertain significance (Dec 21, 2023)
15-74754820-G-T		not specified	Uncertain significance (Sep 16, 2021)
15-74754937-A-G		not specified	Uncertain significance (May 22, 2023)
15-74754939-A-C		not specified	Uncertain significance (Oct 04, 2022)
15-74754996-G-A			Benign (Jun 15, 2018)
15-74755066-G-T		not specified	Uncertain significance (Jul 13, 2022)
15-74755085-T-C			Benign (Dec 31, 2019)
15-74755085-T-T			Benign (Mar 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP1A2	protein_coding	protein_coding	ENST00000343932	6	7359

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.48e-10	0.146	125592	0	156	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.417	338	317	1.07	0.0000204	3372
Missense in Polyphen		112	106.13	1.0553		1201
Synonymous	-0.605	145	136	1.07	0.00000887	1076
Loss of Function	0.460	16	18.1	0.883	9.63e-7	191

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000351	0.000351
Ashkenazi Jewish	0.00387	0.00388
East Asian	0.00136	0.00136
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000484	0.000457
Middle Eastern	0.00136	0.00136
South Asian	0.000788	0.000784
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O- deethylation of phenacetin. {ECO:0000269|PubMed:14725854}.
• Pathway: Benzodiazepine Pathway, Pharmacokinetics;Tryptophan metabolism - Homo sapiens (human);Retinol metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Caffeine metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Imipramine/Desipramine Pathway, Pharmacokinetics;Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Warfarin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Estrogen Metabolism Pathway;Tamoxifen Pathway, Pharmacokinetics;Clopidogrel Pathway, Pharmacokinetics;Erlotinib Pathway, Pharmacokinetics;Caffeine Pathway, Pharmacokinetics;Theophylline Pathway, Pharmacokinetics;Clomipramine Pathway, Pharmacokinetics;Doxepin Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Phenytoin (Antiarrhythmic) Action Pathway;Imipramine Action Pathway;Clopidogrel Metabolism Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Imipramine Metabolism Pathway;Lidocaine (Local Anaesthetic) Metabolism Pathway;Clopidogrel Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Clomipramine Metabolism Pathway;Acetaminophen Metabolism Pathway;Doxepin Metabolism Pathway;Caffeine Metabolism;Fatty Acid Omega Oxidation;Sulindac Metabolic Pathway;Aryl Hydrocarbon Receptor;Lidocaine metabolism;Aryl Hydrocarbon Receptor Pathway;Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Melatonin metabolism and effects;Caffeine and Theobromine metabolism;Liver steatosis AOP;Oxidation by Cytochrome P450;Tryptophan metabolism;Tamoxifen metabolism;Arylamine metabolism;Estrogen metabolism;Aflatoxin B1 metabolism;Metapathway biotransformation Phase I and II;mechanism of acetaminophen activity and toxicity;Phase I - Functionalization of compounds;Methylation;Metabolism of lipids;Phase II - Conjugation of compounds;Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE);Arachidonic acid metabolism;Aromatic amines can be N-hydroxylated or N-dealkylated by CYP1A2;Xenobiotics;Tyrosine metabolism;Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET);Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Biosynthesis of protectins;Biosynthesis of maresin-like SPMs;Biosynthesis of maresins;Biosynthesis of DHA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Vitamin A (retinol) metabolism;Xenobiotics metabolism;Tryptophan degradation;superpathway of tryptophan utilization;Aflatoxin activation and detoxification;melatonin degradation I;superpathway of melatonin degradation;Arachidonic acid metabolism (Consensus)

Recessive Scores

• pRec: 0.722

Intolerance Scores

• loftool: 0.560
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.19

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.112
• ghis: 0.419

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp1a2
• Phenotype: homeostasis/metabolism phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm

Gene ontology

• Biological process: steroid catabolic process;porphyrin-containing compound metabolic process;xenobiotic metabolic process;toxin biosynthetic process;post-embryonic development;alkaloid metabolic process;regulation of gene expression;monoterpenoid metabolic process;drug metabolic process;dibenzo-p-dioxin metabolic process;epoxygenase P450 pathway;electron transport chain;lung development;methylation;response to estradiol;response to lipopolysaccharide;monocarboxylic acid metabolic process;response to immobilization stress;drug catabolic process;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;cellular respiration;heterocycle metabolic process;hydrogen peroxide biosynthetic process;oxidation-reduction process;oxidative demethylation;cellular response to cadmium ion;cellular response to copper ion;oxidative deethylation;omega-hydroxylase P450 pathway
• Cellular component: endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;iron ion binding;electron transfer activity;oxidoreductase 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;demethylase activity;caffeine oxidase activity;aromatase activity