CYP3A4
cytochrome P450 family 3 subfamily A member 4, the group of Cytochrome P450 family 3
Basic information
Region (hg38): 7:99756960-99784248
Previous symbols: [ "CYP3A3" ]
Links
Phenotypes
GenCC
Source:
- vitamin D-dependent rickets, type 3 (Limited), mode of inheritance: AD
- vitamin D-dependent rickets, type 3 (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Vitamin D-dependent rickets, type 3; Drug metabolism, CYP3A4-related | AD | Pharmacogenomic | In Vitamin D-dependent rickets, medical management (eg, with high-dose calcitriol or vitamin D3) has been reporteed as beneficial; For Drug metabolism, CYP3A4-related, selection and dosing of medications (eg,colchicine) may be affected by the presence of variants | General | 9789061; 18973929; 19337788; 19802823; 19907160; 20386561; 21047202; 20437462; 20440227; 21902501; 21902502; 21903774; 21946898; 29461981 |
ClinVar
This is a list of variants' phenotypes submitted to
- Vitamin D-dependent rickets, type 3 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP3A4 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 | |||||
| missense | 10 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 1 | 0 | 8 | 3 | 2 |
Variants in CYP3A4
This is a list of pathogenic ClinVar variants found in the CYP3A4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-99758182-G-T | not specified | Uncertain significance (Aug 25, 2015) | ||
| 7-99758183-G-GT | Likely benign (Oct 31, 2018) | |||
| 7-99760908-T-C | not specified | Uncertain significance (Jan 08, 2024) | ||
| 7-99762032-G-A | Benign (Jun 28, 2018) | |||
| 7-99762140-C-T | not specified | Uncertain significance (Jan 08, 2024) | ||
| 7-99762206-G-A | Likely benign (Apr 19, 2018) | |||
| 7-99762254-T-C | not specified | Uncertain significance (Nov 15, 2021) | ||
| 7-99763843-C-T | tacrolimus response - Metabolism/PK • fentanyl response - Dosage | drug response (Jan 20, 2023) | ||
| 7-99763979-A-G | Vitamin D-dependent rickets, type 3 | Pathogenic (May 04, 2022) | ||
| 7-99767460-G-A | tacrolimus response - Metabolism/PK | drug response (Mar 24, 2021) | ||
| 7-99768384-C-A | not specified | Uncertain significance (May 14, 2024) | ||
| 7-99768410-T-C | Uncertain significance (Sep 01, 2023) | |||
| 7-99768424-T-C | CYP3A4-related disorder | Likely benign (Nov 10, 2023) | ||
| 7-99768445-G-A | Benign (Jun 12, 2018) | |||
| 7-99768448-G-C | not specified | Uncertain significance (Jun 18, 2021) | ||
| 7-99770179-T-A | not specified | Uncertain significance (Mar 28, 2023) | ||
| 7-99780084-A-G | not specified | Uncertain significance (Jun 05, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CYP3A4 | protein_coding | protein_coding | ENST00000336411 | 13 | 27285 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.80e-11 | 0.386 | 125514 | 0 | 233 | 125747 | 0.000927 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.352 | 281 | 265 | 1.06 | 0.0000129 | 3320 |
| Missense in Polyphen | 78 | 89.404 | 0.87244 | 1160 | ||
| Synonymous | 0.382 | 89 | 93.7 | 0.950 | 0.00000461 | 944 |
| Loss of Function | 1.09 | 19 | 24.8 | 0.765 | 0.00000123 | 314 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00113 | 0.00113 |
| Ashkenazi Jewish | 0.00357 | 0.00358 |
| East Asian | 0.00256 | 0.00256 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.000317 | 0.000316 |
| Middle Eastern | 0.00256 | 0.00256 |
| South Asian | 0.00258 | 0.00258 |
| Other | 0.000654 | 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 performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2- exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599). {ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:21576599}.;
- Pathway
- Citalopram Pathway, Pharmacokinetics;Artemisinin and Derivatives Pathway, Pharmacokinetics;Celecoxib Pathway, Pharmacokinetics;Benzodiazepine Pathway, Pharmacokinetics;Retinol metabolism - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Bile secretion - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Linoleic acid metabolism - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Carbamazepine Pathway, Pharmacokinetics;Imipramine/Desipramine Pathway, Pharmacokinetics;Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Losartan Pathway, Pharmacokinetics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Warfarin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Tamoxifen Pathway, Pharmacokinetics;Codeine and Morphine Pathway, Pharmacokinetics;Vinka Alkaloid Pathway, Pharmacokinetics;Gefitinib Pathway, Pharmacokinetics;Proton Pump Inhibitor Pathway, Pharmacokinetics;Anti-diabetic Drug Repaglinide Pathway, Pharmacokinetics;Anti-diabetic Drug Nateglinide Pathway, Pharmacokinetics;Clopidogrel Pathway, Pharmacokinetics;Taxane Pathway, Pharmacokinetics;Erlotinib Pathway, Pharmacokinetics;Fluoxetine Pathway, Pharmacokinetics;Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Caffeine Pathway, Pharmacokinetics;Tramadol Pharmacokinetics;Metformin Pathway, Pharmacodynamic;Nevirapine Pathway, Pharmacokinetics;Theophylline Pathway, Pharmacokinetics;Sorafenib Pharmacokinetics;Clomipramine Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Doxepin Pathway, Pharmacokinetics;Tacrolimus/Cyclosporine Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Venlafaxine Pathway, Pharmacokinetics;Ibuprofen Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacokinetics;Etoposide Pathway, Pharmacokinetics/Pharmacodynamics;Cyclophosphamide Pathway, Pharmacokinetics;Ifosfamide Pathway, Pharmacokinetics;Ibuprofen Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Artemether Metabolism Pathway;Mycophenolic Acid Metabolism Pathway;Fluoxetine Action Pathway;Imipramine Action Pathway;Ibuprofen Metabolism Pathway;Clopidogrel Metabolism Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Celecoxib Action Pathway;Methadone Metabolism Pathway;Imipramine Metabolism Pathway;Lidocaine (Local Anaesthetic) Metabolism Pathway;Codeine Metabolism Pathway;Clopidogrel Action Pathway;Irinotecan Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Tamoxifen Action Pathway;Methadone Action Pathway;Codeine Action Pathway;Tramadol Metabolism Pathway;Venlafaxine Metabolism Pathway;Carbamazepine Metabolism Pathway;Felbamate Metabolism Pathway;Prednisone Metabolism Pathway;Clomipramine Metabolism Pathway;Cyclophosphamide Action Pathway;Prednisone Action Pathway;Etoposide Action Pathway;Teniposide Action Pathway;Ifosfamide Action Pathway;Sorafenib Metabolism Pathway;Acetaminophen Metabolism Pathway;Doxepin Metabolism Pathway;Vitamin A Deficiency;Fluoxetine Metabolism Pathway;Celecoxib Metabolism Pathway;Nevirapine Metabolism Pathway;Caffeine Metabolism;Teniposide Metabolism Pathway;Irinotecan Metabolism Pathway;Etoposide Metabolism Pathway;Tamoxifen Metabolism Pathway;Cyclophosphamide Metabolism Pathway;Ifosfamide Metabolism Pathway;Retinol Metabolism;Codeine and Morphine Metabolism;Fatty Acid Omega Oxidation;Drug Induction of Bile Acid Pathway;Irinotecan Pathway;Nifedipine Activity;Lidocaine metabolism;Felbamate Metabolism;Cocaine metabolism;Liver X Receptor Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Vitamin D Receptor Pathway;Farnesoid X Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Cannabinoid receptor signaling;Angiopoietin Like Protein 8 Regulatory Pathway;Liver steatosis AOP;Oxidation by Cytochrome P450;Tryptophan metabolism;Tamoxifen metabolism;Benzo(a)pyrene metabolism;Estrogen metabolism;Aflatoxin B1 metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Xenobiotics;Tyrosine metabolism;Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Biosynthesis of maresin-like SPMs;Biosynthesis of maresins;Biosynthesis of DHA-derived SPMs;Biosynthesis of specialized proresolving mediators (SPMs);Fatty acid metabolism;Linoleate metabolism;Bile acid biosynthesis;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;Aflatoxin activation and detoxification;Arachidonic acid metabolism
(Consensus)
Recessive Scores
- pRec
- 0.582
Intolerance Scores
- loftool
- 0.930
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.65
Haploinsufficiency Scores
- pHI
- 0.0695
- hipred
- N
- hipred_score
- 0.209
- ghis
- 0.473
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.00151
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Gene ontology
- Biological process
- lipid hydroxylation;lipid metabolic process;steroid catabolic process;xenobiotic metabolic process;steroid metabolic process;androgen metabolic process;alkaloid catabolic process;monoterpenoid metabolic process;drug metabolic process;calcitriol biosynthetic process from calciol;vitamin D metabolic process;drug catabolic process;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;heterocycle metabolic process;oxidation-reduction process;oxidative demethylation
- Cellular component
- cytoplasm;endoplasmic reticulum membrane;integral component of membrane;organelle membrane;intracellular membrane-bounded organelle
- Molecular function
- monooxygenase activity;steroid binding;iron ion binding;steroid hydroxylase 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;oxygen binding;enzyme binding;heme binding;vitamin D3 25-hydroxylase activity;caffeine oxidase activity;testosterone 6-beta-hydroxylase activity;vitamin D 24-hydroxylase activity;estrogen 16-alpha-hydroxylase activity