CYP2D6
Cytochrome P450 Family 2 Subfamily D Member 6
Gene Information Card
| Symbol | CYP2D6 |
|---|---|
| Full Name | Cytochrome P450 Family 2 Subfamily D Member 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.2 |
| NCBI Gene ID | 1565 ncbi.nlm.nih.gov/gene/1565 |
| Ensembl ID | ENSG00000100197 |
| UniProt ID | P10635 |
| OMIM ID | 124030 |
| HGNC ID | 2625 |
| Aliases | CYP2D, CYP2D7, CYP2D8, P450-DB1, P450C2D |
Description
CYP2D6 encodes a member of the cytochrome P450 superfamily of enzymes, which are involved in the metabolism of many endogenous compounds and xenobiotics. This enzyme is responsible for the oxidative metabolism of approximately 25% of clinically used drugs, including antidepressants, antipsychotics, beta-blockers, and opioids. CYP2D6 is highly polymorphic, with over 100 known allelic variants that result in four major metabolizer phenotypes: poor, intermediate, extensive (normal), and ultrarapid. These phenotypes significantly influence drug efficacy and toxicity, making CYP2D6 a key gene in pharmacogenomics.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Drug-induced liver injury | Impaired CYP2D6 activity leads to accumulation of toxic drug metabolites | ClinVar, PMID: 25741868 |
| Parkinson's disease | CYP2D6 poor metabolizer status associated with increased risk | OMIM, PMID: 10408771 |
| Breast cancer (tamoxifen response) | CYP2D6*4 variant reduces conversion of tamoxifen to active endoxifen, affecting treatment outcome | ClinVar, PMID: 19858482 |
| Opioid dependence (codeine toxicity) | Ultrarapid metabolizers convert codeine to morphine excessively, risking respiratory depression | ClinVar, PMID: 16772608 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Small intestine | 3.2 | Medium |
| Kidney | 1.8 | Low |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 8.1 | Hepatocellular carcinoma cell line |
| Caco-2 | 2.4 | Colorectal adenocarcinoma cell line |
| HEK293 | 0.3 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CYP2D6*4 (1846G>A) | SNP | ~20% in Caucasians | Splicing defect, loss of function |
| CYP2D6*10 (100C>T) | SNP | ~50% in East Asians | Reduced enzyme activity |
| CYP2D6*17 (1023C>T) | SNP | ~34% in Africans | Reduced substrate affinity |
| CYP2D6*2xN | Gene duplication | 1-10% in various populations | Increased enzyme activity (ultrarapid metabolizer) |
Mutation functional classification
Loss of Function (LOF)
CYP2D6*4, *5 (gene deletion), *6, *7, *8, *11, *12, *14, *15, *18, *19, *20, *21, *38, *40, *42, *44, *56, *62 result in absent or severely reduced enzyme activity.
Gain of Function (GOF)
CYP2D6*1xN, *2xN (gene duplications or multiplications) lead to increased enzyme activity, classified as ultrarapid metabolizer phenotype.
Dominant Negative (DN)
No well-established dominant-negative variants reported for CYP2D6.
View complete mutation data：
Gene Ontology (GO)
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
CYP2D6 is a 497-amino acid microsomal hemoprotein that functions as a monooxygenase. It is primarily expressed in the liver and catalyzes the oxidative metabolism of a wide range of drugs and endogenous substrates. The enzyme contains a heme-binding domain and a conserved P450 cysteine heme-iron ligand signature. Its three-dimensional structure has been resolved, revealing a flexible active site that accommodates diverse substrates. CYP2D6 activity is highly variable due to genetic polymorphisms, which are a major cause of interindividual differences in drug response.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP2D6 Knockout HEK293 Cell Line | EDJ-KQ4406 | Human | 1565 | Details Get a Quote |
| CYP2D6 Knockout HeLa Cell Line | EDJ-KQ26931 | Human | 1565 | Details Get a Quote |
| CYP2D6 Knockout A-549 Cell Line | EDJ-KQ61514 | Human | 1565 | Details Get a Quote |
| CYP2D6 Knockout HCT 116 Cell Line | EDJ-KQ70007 | Human | 1565 | Details Get a Quote |
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