| HGNC Family | Cytochrome P450s (CYP) |
| Name | cytochrome P450, family 2, subfamily D, polypeptide 6 |
| Description | This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCytochrome P450 2D6 (CYP2D6) is a heme‐containing enzyme that plays a central role in the oxidative metabolism of a wide range of drugs. Structural studies have defined its characteristic P450 fold and pinpointed key active‐site residues that govern substrate recognition and binding. In addition, extensive population‐based investigations have revealed striking interindividual and interethnic differences in CYP2D6 allele frequencies and gene‐copy number variations that underlie its considerable functional variability. These broad differences not only affect the overall metabolic capacity of the enzyme but also have important implications for personalized drug therapy in diverse clinical settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA particularly well‐documented aspect of CYP2D6’s function is its role in the biotransformation of prodrugs into active metabolites. For example, CYP2D6 converts tamoxifen into its potent antiestrogenic metabolites—most notably endoxifen—a process that is crucial for tamoxifen’s therapeutic efficacy in breast cancer. Genetic polymorphisms in CYP2D6, as well as co‐administration of enzyme inhibitors, have been shown to significantly modulate plasma levels of these active compounds, thus affecting clinical outcomes. Such findings have made CYP2D6 one of the most extensively studied enzymes in pharmacogenetics, with studies demonstrating its impact on multiple aspects of drug response and treatment efficacy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in anticancer therapy, CYP2D6 is critically involved in the metabolism of drugs used in pain management and psychiatric care. It is responsible for converting opioids such as codeine into morphine and activating tramadol via O‑demethylation, with genetic differences leading to markedly altered analgesic responses and adverse event profiles. Variants that result in poor or ultra‐rapid metabolism may predispose patients to therapeutic failure or drug toxicity when standard dosages are applied. Moreover, CYP2D6-mediated metabolism extends to several antidepressants and antipsychotics, thereby influencing both efficacy and tolerability, and even contributing (as observed in novel animal models) to immune-mediated phenomena. Collectively, these studies underscore how CYP2D6 function serves as a linchpin in determining individual drug response across multiple therapeutic areas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "33", "end_ref": "50"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "U M Zanger, J Fischer, S Raimundo, et al. 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| Synonyms | CYP2D7BP, CYP2D7P2, CYPIID6, CYP2D8P2, CYP2DL1, CPD6, P450-DB1 |
| Proteins | CP2D6_HUMAN |
| NCBI Gene ID | 1565 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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CYP2D6 has 6,681 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 81 datasets.
Click the + buttons to view associations for CYP2D6 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by CYP2D6 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of CYP2D6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq | tissue samples with high or low expression of CYP2D6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of CYP2D6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of CYP2D6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of CYP2D6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of CYP2D6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of CYP2D6 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of CYP2D6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ClinVar Gene-Phenotype Associations | phenotypes associated with CYP2D6 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of CYP2D6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing CYP2D6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores | cellular components containing CYP2D6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with CYP2D6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of CYP2D6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with CYP2D6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with CYP2D6 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with CYP2D6 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by CYP2D6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with CYP2D6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with CYP2D6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with CYP2D6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with CYP2D6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with CYP2D6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| DrugBank Drug Targets | interacting drugs for CYP2D6 protein from the curated DrugBank Drug Targets dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at CYP2D6 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of CYP2D6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of CYP2D6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GAD Gene-Disease Associations | diseases associated with CYP2D6 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with CYP2D6 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of CYP2D6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with CYP2D6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing CYP2D6 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of CYP2D6 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving CYP2D6 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing CYP2D6 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by CYP2D6 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of CYP2D6 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CYP2D6 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of CYP2D6 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| HMDB Metabolites of Enzymes | interacting metabolites for CYP2D6 protein from the curated HMDB Metabolites of Enzymes dataset. | |
| HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of CYP2D6 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of CYP2D6 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of CYP2D6 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuBMAP ASCT+B Annotations | cell types associated with CYP2D6 gene from the HuBMAP ASCT+B dataset. | |
| HuBMAP ASCT+B Augmented with RNA-seq Coexpression | cell types associated with CYP2D6 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with CYP2D6 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for CYP2D6 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of CYP2D6 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways | pathways involving CYP2D6 protein from the KEGG Pathways dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of CYP2D6 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles | cell lines with high or low expression of CYP2D6 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of CYP2D6 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing CYP2D6 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain CYP2D6 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MiRTarBase microRNA Targets | microRNAs targeting CYP2D6 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of CYP2D6 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MSigDB Cancer Gene Co-expression Modules | co-expressed genes for CYP2D6 from the MSigDB Cancer Gene Co-expression Modules dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of CYP2D6 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| NURSA Protein Complexes | protein complexs containing CYP2D6 protein recovered by IP-MS from the NURSA Protein Complexes dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with CYP2D6 gene from the curated OMIM Gene-Disease Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for CYP2D6 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving CYP2D6 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving CYP2D6 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2014 | pathways involving CYP2D6 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving CYP2D6 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of CYP2D6 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of CYP2D6 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at CYP2D6 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of CYP2D6 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of CYP2D6 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of CYP2D6 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of CYP2D6 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with CYP2D6 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| WikiPathways Pathways 2014 | pathways involving CYP2D6 protein from the Wikipathways Pathways 2014 dataset. | |
| WikiPathways Pathways 2024 | pathways involving CYP2D6 protein from the WikiPathways Pathways 2024 dataset. | |
