Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57).
Article Details
- CitationCopy to clipboard
Sakuyama K, Sasaki T, Ujiie S, Obata K, Mizugaki M, Ishikawa M, Hiratsuka M
Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57).
Drug Metab Dispos. 2008 Dec;36(12):2460-7. doi: 10.1124/dmd.108.023242. Epub 2008 Sep 10.
- PubMed ID
- 18784265 [ View in PubMed]
- Abstract
Cytochrome P450 2D6 (CYP2D6) is an enzyme of potential importance for the metabolism of drugs used clinically, and it exhibits genetic polymorphism with interindividual differences in metabolic activity. To date, 21 CYP2D6 allelic variants have been identified in the Japanese population. The aim of this study was to investigate the functional characterization of CYP2D6 variants identified in Japanese subjects. Wild-type CYP2D6 and its variants, namely, CYP2D6.2, CYP2D6.10, CYP2D6.14A, CYP2D6.14B, CYP2D6.18, CYP2D6.27, CYP2D6.36, CYP2D6.39, CYP2D6.47, CYP2D6.48, CYP2D6.49, CYP2D6.50, CYP2D6.51, CYP2D6.53, CYP2D6.54, CYP2D6.55, and CYP2D6.57 were transiently expressed in COS-7 cells, and enzymatic activities of the CYP2D6 variant proteins were characterized using bufuralol and dextromethorphan. Functional characterization of 17 CYP2D6 variants revealed an absence of enzyme activity in four (CYP2D6.14A, CYP2D6.36, CYP2D6.47, and CYP2D6.57), low activity in eight (CYP2D6.10, CYP2D6.14B, CYP2D6.18, CYP2D6.49, CYP2D6.50, CYP2D6.51, CYP2D6.54, and CYP2D6.55), and high activity in one (CYP2D6.53) compared with the wild type. Analysis of CYP2D6 variant proteins can be useful for predicting CYP2D6 phenotypes and could be applied to personalized drug therapy.
DrugBank Data that Cites this Article
- Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Metoprolol Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
ADR Inferred Increased risk of slow heart rate (bradycardia) Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Venlafaxine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements Details Codeine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Amitriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Imipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements Details Dextromethorphan Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Nortriptyline Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Tamoxifen Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor response to drug treatment, shorter time to relapse Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Desipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Clomipramine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*14A Not Available - 1758G>A (rs5030865)
Effect Inferred Poor drug metabolizer, increased side effects. Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*36 Not Available - 100C>T (rs1065852)
- -1426C>T
- variable number of A’s in the region -1258 to -1237a
Effect Inferred Poor drug metabolizer, increased side effects. Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*47 Not Available - 100C>T (rs1065852)
- -1426C>T
- -1235A>G
Effect Inferred Poor drug metabolizer, increased side effects. Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*51 Not Available - -1584C>G
- -1235A>G
- -740C>T
Effect Inferred Poor drug metabolizer, increased side effects. Details Atomoxetine Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635CYP2D6*57 Not Available - 100C>T
- 310G>T
- 843T>G
Effect Inferred Poor drug metabolizer, increased side effects. Details