CYP2D6

cytochrome P450 family 2 subfamily D member 6, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 22:42126498-42130865

Previous symbols: [ "CYP2DL1", "CYP2D7P2", "CYP2D7BP", "CYP2D8P2", "CYP2D7AP" ]

Links

ENSG00000100197 ∙ NCBI:1565 ∙ OMIM:124030 ∙ HGNC:2625 ∙ Uniprot:P10635 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Drug metabolism, CYP2CD6-related	AD	Pharmacogenomic	Variants may affect the metabolism of mulitple drugs including debrosoquine, sparteine, nortriptyline, codeine, tamoxifen	General	4082245; 1978251; 1673290; 8093319; 7903454; 9012401; 11940091; 15625333; 19809024 ; 22406651; 22733239; 22775532

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2D6 gene.

• not provided (24 variants)
• Inborn genetic diseases (20 variants)
• Tramadol response (8 variants)
• not specified (7 variants)
• Debrisoquine, poor metabolism of (5 variants)
• Tamoxifen response (4 variants)
• Deutetrabenazine response (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2D6 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				3		3
missense			19	12	1	32
nonsense				1		1
start loss						0
frameshift				3		3
inframe indel				1		1
splice donor/acceptor (+/-2bp)				2		2
splice region						0
non coding				4		4
Total	0	0	19	26	1

Variants in CYP2D6

This is a list of pathogenic ClinVar variants found in the CYP2D6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-42126532-A-G		Tramadol response	drug response (Apr 28, 2018)
22-42126536-T-C		Tramadol response	drug response (Apr 28, 2018)
22-42126597-C-T		not specified	Uncertain significance (Mar 23, 2022)
22-42126611-C-G		not specified	Benign; other (Jan 17, 2024)
22-42126611-C-C		not specified • Tramadol response	Benign/Likely benign (Dec 30, 2023)
22-42126627-A-G		Tramadol response	drug response (Apr 28, 2018)
22-42126667-C-T		Tramadol response	drug response (Apr 28, 2018)
22-42126682-C-G		not specified	Uncertain significance (Dec 19, 2023)
22-42126736-G-A			Likely benign (Dec 01, 2022)
22-42126744-C-T		not specified	Uncertain significance (Jun 22, 2023)
22-42126747-G-A			drug response (-)
22-42126749-C-T			drug response (-)
22-42126753-C-T		Tramadol response	drug response (Apr 28, 2018)
22-42126803-T-C		Tramadol response	drug response (Apr 28, 2018)
22-42126813-C-T		Tramadol response	drug response (Apr 28, 2018)
22-42126819-A-G		Tramadol response	drug response (Apr 28, 2018)
22-42126865-A-T		Tramadol response	drug response (Apr 28, 2018)
22-42126881-T-C		Tramadol response	drug response (Apr 28, 2018)
22-42126925-C-T		not specified	Uncertain significance (Jan 02, 2024)
22-42126931-G-A		Tramadol response	drug response (Apr 28, 2018)
22-42126944-C-T		Tramadol response	drug response (Apr 28, 2018)
22-42126963-C-T			Likely benign (Apr 01, 2023)
22-42127001-G-G		Tramadol response	drug response (Apr 28, 2018)
22-42127027-G-A		Tramadol response	drug response (Apr 28, 2018)
22-42127169-C-T		Tramadol response	drug response (Apr 28, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2D6	protein_coding	protein_coding	ENST00000360608	9	4408

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.08e-25	0.00000257	120562	166	4989	125717	0.0207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.00	403	305	1.32	0.0000219	3074
Missense in Polyphen		130	101.19	1.2847		1069
Synonymous	-3.99	200	140	1.43	0.0000108	1037
Loss of Function	-2.57	31	18.9	1.64	0.00000110	188

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0201	0.0191
Ashkenazi Jewish	0.0131	0.0127
East Asian	0.00298	0.00283
Finnish	0.0572	0.0559
European (Non-Finnish)	0.0288	0.0275
Middle Eastern	0.00298	0.00283
South Asian	0.00496	0.00478
Other	0.0172	0.0164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. {ECO:0000269|PubMed:16352597}.
• Pathway: Citalopram Pathway, Pharmacokinetics;Celecoxib Pathway, Pharmacokinetics;Benzodiazepine Pathway, Pharmacokinetics;Serotonergic synapse - Homo sapiens (human);Metabolism of xenobiotics by cytochrome P450 - Homo sapiens (human);Drug metabolism - cytochrome P450 - Homo sapiens (human);Imipramine/Desipramine Pathway, Pharmacokinetics;Imatinib Pathway, Pharmacokinetics/Pharmacodynamics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Fluvastatin Pathway, Pharmacokinetics;Phenytoin Pathway, Pharmacokinetics;Tamoxifen Pathway, Pharmacokinetics;Codeine and Morphine Pathway, Pharmacokinetics;Gefitinib Pathway, Pharmacokinetics;Fluoxetine Pathway, Pharmacokinetics;Tramadol Pharmacokinetics;Nevirapine Pathway, Pharmacokinetics;Clomipramine Pathway, Pharmacokinetics;Doxepin Pathway, Pharmacokinetics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Venlafaxine Pathway, Pharmacokinetics;Fluoxetine Action Pathway;Citalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Celecoxib Action Pathway;Methadone Metabolism Pathway;Imipramine Metabolism Pathway;Desipramine Metabolism Pathway;Citalopram Metabolism Pathway;Codeine Metabolism Pathway;Tamoxifen Action Pathway;Methadone Action Pathway;Codeine Action Pathway;Tramadol Metabolism Pathway;Venlafaxine Metabolism Pathway;Clomipramine Metabolism Pathway;Acetaminophen Metabolism Pathway;Doxepin Metabolism Pathway;Fluoxetine Metabolism Pathway;Celecoxib Metabolism Pathway;Nevirapine Metabolism Pathway;Tamoxifen Metabolism Pathway;Codeine and Morphine Metabolism;Fatty Acid Omega Oxidation;Aripiprazole Metabolic Pathway;Vitamin D Receptor Pathway;Melatonin metabolism and effects;Oxidation by Cytochrome P450;Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Xenobiotics;Tyrosine metabolism;Fatty acids;Androgen and estrogen biosynthesis and metabolism;Miscellaneous substrates;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;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;CYP2E1 reactions;Arachidonic acid metabolism (Consensus)

Intolerance Scores

• rvis_EVS: 1.77
• rvis_percentile_EVS: 96.77

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.146
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.149

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: organic acid metabolic process;xenobiotic metabolic process;steroid metabolic process;coumarin metabolic process;alkaloid metabolic process;alkaloid catabolic process;monoterpenoid metabolic process;drug metabolic process;arachidonic acid metabolic process;isoquinoline alkaloid metabolic process;drug catabolic process;exogenous drug catabolic process;long-chain fatty acid biosynthetic process;heterocycle metabolic process;negative regulation of binding;oxidation-reduction process;oxidative demethylation;negative regulation of cellular organofluorine metabolic process
• Cellular component: cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;iron ion binding;drug 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;heme binding;aromatase activity