CYP1A2
cytochrome P450 family 1 subfamily A member 2, the group of Cytochrome P450 family 1
Basic information
Region (hg38): 15:74748845-74756607
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| 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
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 | 3 | |||||
| missense | 17 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 2 | |||||
| Total | 0 | 0 | 17 | 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) | ||
| 15-74751284-C-A | not specified | Uncertain significance (Apr 01, 2024) | ||
| 15-74751805-G-A | not specified | Uncertain significance (Mar 01, 2024) | ||
| 15-74752168-C-A | not specified | Uncertain significance (Mar 15, 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) |
GnomAD
Source:
| 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:
- 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