CYP3A4
Cytochrome P450 Family 3 Subfamily A Member 4
Gene Information Card
| Symbol | CYP3A4 |
|---|---|
| Full Name | Cytochrome P450 Family 3 Subfamily A Member 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 1576 ncbi.nlm.nih.gov/gene/1576 |
| Ensembl ID | ENSG00000160868 |
| UniProt ID | P08684 |
| OMIM ID | 124010 |
| HGNC ID | 2637 |
| Aliases | CYP3A4, CYP3A, CYPIIIA4, P450C3, P450PCN1, NF-25, CP33, CYP3A4*1B |
Description
CYP3A4 encodes a member of the cytochrome P450 superfamily of enzymes, which are heme-thiolate monooxygenases involved in the metabolism of endogenous compounds and xenobiotics. CYP3A4 is the most abundant cytochrome P450 in the human liver and intestine, responsible for the oxidative metabolism of approximately 50% of clinically used drugs, including statins, calcium channel blockers, immunosuppressants, and many chemotherapeutic agents. The gene exhibits significant interindividual variability in expression and activity due to genetic polymorphisms, environmental factors, and drug interactions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Drug-induced liver injury | CYP3A4 metabolizes numerous drugs; reduced activity can lead to accumulation and hepatotoxicity. | ClinVar |
| Prostate cancer | Polymorphisms in CYP3A4 may alter androgen metabolism and influence cancer risk. | OMIM |
| Acute myeloid leukemia | CYP3A4 expression affects the metabolism of chemotherapeutic agents like etoposide. | COSMIC |
| Hypertension | CYP3A4 metabolizes calcium channel blockers; variants may affect drug response. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 100.0 | High |
| Small intestine | 60.0 | High |
| Kidney | 20.0 | Medium |
| Colon | 15.0 | Medium |
| Lung | 5.0 | Low |
| Prostate | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 80.0 | Hepatocellular carcinoma cell line; moderate CYP3A4 expression |
| Caco-2 | 45.0 | Colorectal adenocarcinoma; intestinal-like expression |
| MCF7 | 2.0 | Breast cancer; low expression |
| A549 | 1.5 | Lung carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CYP3A4*1B (rs2740574) | SNP (promoter) | 2-5% in Caucasians | Increased transcriptional activity; altered drug metabolism |
| CYP3A4*2 (rs55785340) | Missense (S222P) | <1% | Reduced enzyme activity |
| CYP3A4*3 (rs4986910) | Missense (M445T) | <1% | Reduced enzyme activity |
| CYP3A4*17 (rs4987161) | Missense (F189S) | <1% | Reduced enzyme activity |
| CYP3A4*20 | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
CYP3A4*20 (frameshift) and certain missense variants (e.g., *2, *3, *17) result in reduced or absent enzyme activity, leading to impaired drug metabolism.
Gain of Function (GOF)
CYP3A4*1B (promoter SNP) is associated with increased transcriptional activity and enhanced drug clearance.
Dominant Negative (DN)
No dominant-negative variants have been reported for CYP3A4.
View complete mutation data：
Gene Ontology (GO)
| • monooxygenase activity (GO:0004497) | • iron ion binding (GO:0005506) |
| • steroid hydroxylase activity (GO:0008395) | • oxidoreductase activity (GO:0016491) |
| • heme binding (GO:0020037) | • oxidation-reduction process (GO:0055114) |
Pathways
• Drug metabolism - cytochrome P450 (KEGG: hsa00982)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
• Chemical carcinogenesis (KEGG: hsa05204)
• Retinol metabolism (KEGG: hsa00830)
• Linoleic acid metabolism (KEGG: hsa00591)
Protein Summary
CYP3A4 is a 502-amino acid microsomal heme protein (UniProt P08684) localized to the endoplasmic reticulum. It catalyzes the NADPH-dependent oxidative metabolism of a wide range of substrates, including steroids, bile acids, and drugs. The protein contains a conserved heme-binding domain and a substrate recognition site that accommodates structurally diverse molecules. Post-translational modifications include phosphorylation, which may modulate activity. CYP3A4 expression is regulated by nuclear receptors such as PXR and CAR.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP3A4 Knockout HEK293 Cell Line | EDJ-KQ1389 | Human | 1576 | Details Get a Quote |
| CYP3A43 Knockout HEK293 Cell Line | EDJ-KQ13073 | Human | 64816 | Details Get a Quote |
| CYP3A4 Knockout HeLa Cell Line | EDJ-KQ53053 | Human | 1576 | Details Get a Quote |
| CYP3A43 Knockout HeLa Cell Line | EDJ-KQ57085 | Human | 64816 | Details Get a Quote |
| CYP3A4 Knockout A-549 Cell Line | EDJ-KQ61518 | Human | 1576 | Details Get a Quote |
| CYP3A43 Knockout A-549 Cell Line | EDJ-KQ65597 | Human | 64816 | Details Get a Quote |
| CYP3A4 Knockout HCT 116 Cell Line | EDJ-KQ70010 | Human | 1576 | Details Get a Quote |
| CYP3A43 Knockout HCT 116 Cell Line | EDJ-KQ74026 | Human | 64816 | Details Get a Quote |
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