Pharmacogenomics. Knowledge. Implementation.

Haplotype
CYP2D6 *6
part of CYP2D6 Cytochrome P450 Nomenclature DB Haplotype Set

Clinical PGx
Overview
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Clinical Annotations

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Clinical Annotation for CYP2D61, CYP2D610, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D6*6, paroxetine, Depressive Disorder, Major, Mental Disorders and Obsessive-Compulsive Disorder (level 1A Efficacy, Toxicity/ADR, Metabolism/PK)

Level of Evidence: Level 1A
Type: Efficacy, Toxicity/ADR, Metabolism/PK
Variant: *1, *10, *1xN, *2, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major, Mental Disorders, Obsessive-Compulsive Disorder
OMB Race: Mixed Population
Race Notes: Asian, White and Unknown

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D63, CYP2D64, CYP2D65, CYP2D66, fluvoxamine, Depressive Disorder, Depressive Disorder, Major, Mental Disorders and Obsessive-Compulsive Disorder (level 1A Efficacy, Toxicity/ADR, Metabolism/PK)

Level of Evidence: Level 1A
Type: Efficacy, Toxicity/ADR, Metabolism/PK
Variant: *1, *10, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Depressive Disorder, Major, Mental Disorders, Obsessive-Compulsive Disorder
OMB Race: Mixed Population
Race Notes: Asian, White, Unknown

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D641, CYP2D65, CYP2D66, amitriptyline, Depressive Disorder, Major, Mental Disorders and Mood Disorders (level 1A Efficacy, Toxicity/ADR)

Level of Evidence: Level 1A
Type: Efficacy, Toxicity/ADR
Variant: *1, *10, *1xN, *2, *2xN, *3, *4, *41, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major, Mental Disorders, Mood Disorders
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D6*6, nortriptyline and Depressive Disorder, Major (level 1A Efficacy, Toxicity/ADR, Metabolism/PK)

Level of Evidence: Level 1A
Type: Efficacy, Toxicity/ADR, Metabolism/PK
Variant: *1, *10, *1xN, *2, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major
OMB Race: Mixed Population
Race Notes: Asian, Mixed, and White

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D617, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D640, CYP2D641, CYP2D65, CYP2D66, codeine and Pain (level 1A Efficacy, Toxicity/ADR)

Level of Evidence: Level 1A
Type: Efficacy, Toxicity/ADR
Variant: *1, *10, *17, *1xN, *2, *2xN, *3, *4, *40, *41, *5, *6
Genes: CYP2D6
Phenotypes: Pain
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D6*6, tramadol and Pain (level 1B Dosage, Efficacy, Toxicity/ADR)

Level of Evidence: Level 1B
Type: Dosage, Efficacy, Toxicity/ADR
Variant: *1, *10, *1xN, *2, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Pain
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, oxycodone and Pain (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: *1, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Pain
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D6*6, mirtazapine (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: *1, *1xN, *2xN, *3, *4, *5, *6
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D63, CYP2D64, CYP2D641, CYP2D65, CYP2D6*6, venlafaxine, Depressive Disorder and Obsessive-Compulsive Disorder (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: *1, *10, *3, *4, *41, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Obsessive-Compulsive Disorder
OMB Race: Mixed Population
Race Notes: White, Asian, Unknown

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Clinical Annotation for CYP2D61, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, trimipramine (level 2A)

Level of Evidence: Level 2A
Type: Other
Variant: *1, *2xN, *3, *4, *5, *6
Genes: CYP2D6
OMB Race: Unknown

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, clomipramine, Depressive Disorder, Major and Obsessive-Compulsive Disorder (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: *1, *1xN, *2, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major, Obsessive-Compulsive Disorder
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, imipramine and Depressive Disorder, Major (level 2A Dosage)

Level of Evidence: Level 2A
Type: Dosage
Variant: *1, *1xN, *2, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major
OMB Race: Mixed Population
Race Notes: Asian, White, Unknown

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D614, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, risperidone, Psychotic Disorders and Schizophrenia (level 2A)

Level of Evidence: Level 2A
Type: Other
Variant: *1, *10, *14, *1xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Psychotic Disorders, Schizophrenia
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D617, CYP2D629, CYP2D63, CYP2D631, CYP2D635, CYP2D64, CYP2D641, CYP2D65, CYP2D66, CYP2D69, metoprolol and Hypertension (level 2A Efficacy, Metabolism/PK)

Level of Evidence: Level 2A
Type: Efficacy, Metabolism/PK
Variant: *1, *10, *17, *29, *3, *31, *35, *4, *41, *5, *6, *9
Genes: CYP2D6
Phenotypes: Hypertension
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D63, CYP2D64, CYP2D641, CYP2D65, CYP2D6*6, tamoxifen and Breast Neoplasms (level 2A Efficacy, Metabolism/PK)

Level of Evidence: Level 2A
Type: Efficacy, Metabolism/PK
Variant: *1, *10, *3, *4, *41, *5, *6
Genes: CYP2D6
Phenotypes: Breast Neoplasms
OMB Race: Mixed Population
Race Notes: White, Mixed, Unknown, Asian

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Clinical Annotation for rs5030655 (CYP2D6), metoprolol (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs5030655
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for rs5030655 (CYP2D6), venlafaxine, Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea and Vomiting (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: rs5030655
Genes: CYP2D6
Phenotypes: Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting
OMB Race: White

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Clinical Annotation for rs5030655 (CYP2D6), antipsychotics (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: rs5030655
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D63, CYP2D64, CYP2D65, CYP2D66, risperidone and Schizophrenia (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *10, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Schizophrenia
OMB Race: Unknown

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D641, CYP2D65, CYP2D6*6, galantamine and Dementia (level 3 Metabolism/PK)

Level of Evidence: Level 3
Type: Metabolism/PK
Variant: *1, *1xN, *3, *4, *41, *5, *6
Genes: CYP2D6
Phenotypes: Dementia
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D62, CYP2D63, CYP2D64, CYP2D641, CYP2D65, CYP2D66, citalopram, escitalopram and Depressive Disorder, Major (level 3 Efficacy, Toxicity/ADR)

Level of Evidence: Level 3
Type: Efficacy, Toxicity/ADR
Variant: *1, *10, *2, *3, *4, *41, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62xN, CYP2D63, CYP2D64, CYP2D65, CYP2D6*6, fluoxetine, Depressive Disorder, Major, Mental Disorders, Mood Disorders and Obsessive-Compulsive Disorder (level 3 Metabolism/PK)

Level of Evidence: Level 3
Type: Metabolism/PK
Variant: *1, *1xN, *2xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major, Mental Disorders, Mood Disorders, Obsessive-Compulsive Disorder
OMB Race: Mixed Population
Race Notes: White and unknown

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Clinical Annotation for CYP2D610, CYP2D614, CYP2D63, CYP2D64, CYP2D65, CYP2D66, CYP2D6*7, antipsychotics and Dystonia (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: *10, *14, *3, *4, *5, *6, *7
Genes: CYP2D6
Phenotypes: Dystonia
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D62, CYP2D64, CYP2D641, CYP2D65, CYP2D6*6, aripiprazole (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *10, *2, *4, *41, *5, *6
Genes: CYP2D6
OMB Race: Unknown

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D614, CYP2D62, CYP2D63, CYP2D64, CYP2D641, CYP2D64xN, CYP2D65, CYP2D66, gefitinib, Adenocarcinoma and Carcinoma, Non-Small-Cell Lung (level 3 Toxicity/ADR, Metabolism/PK)

Level of Evidence: Level 3
Type: Toxicity/ADR, Metabolism/PK
Variant: *1, *10, *14, *2, *3, *4, *41, *4xN, *5, *6
Genes: CYP2D6
Phenotypes: Adenocarcinoma, Carcinoma, Non-Small-Cell Lung
OMB Race: Mixed Population

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D63, CYP2D64, CYP2D65, CYP2D66, donepezil and Alzheimer Disease (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *1xN, *3, *4, *5, *6
Genes: CYP2D6
Phenotypes: Alzheimer Disease
OMB Race: Mixed Population
Race Notes: n=1 Arabian, n=127 Caucasian.

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Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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Overview

HGVS representation	NC_000022.10:g.[42525086_42525086delA]
Translation Table	This haplotype is part of the set "CYP2D6 Cytochrome P450 Nomenclature DB Haplotype Set". There is a full translation table for CYP2D6 Cytochrome P450 Nomenclature DB Haplotype Set Download Translation Table

Alleles

Any chromosomal positions listed below are assumed to be on the GRCh38 assembly. Be aware, the assembly may differ for variants elsewhere on the PharmGKB site.

Variant Location	Allele	Reference Allele
rs5030655	delA	A

Variant Annotations

Haplotype Annotations

PharmGKB haplotype annotations provide information about haplotype-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.

Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.

List of all variant annotations for CYP2D6*6

There are direct annotations for this haplotype. Register or sign in to see them.

VIP Annotation

CYP2D6*6 [Article:7951238] is yet another non-functional haplotype of CYP2D6. Similar to CYP2D6*3, CYP2D6*6 is caused by a frameshift mutation that results in a truncated and non-functional CYP2D6 protein [Article:7951238]. CYP2D6*6 is found primarily in Caucasian populations, although with a low allele frequency when compared with the more common CYP2D6*4 and CYP2D6*5 [Articles:11972444, 17301689] (see allele frequency table).

Allele frequency table

Population	\*1	\*2	\*3	\*4	\*5	\*6	\*9	\*10	\*17	\*29	\*41	UM	References
European Caucasian	.33-.36	.22-.33	.01-.04	.12-.21	.02-.07	.01	0-.02	.01-.02	0	N/D	N/D	.02	[Articles:9241659, 9012401, 1681816, 7909282, 7697944, 9511177]
US Caucasian	.36-.40	.26-.37	.01-.02	.18-.23	.02-.05	.01	.02-.03	.02-.08	0	N/D	N/D	.01	[Articles:8098046, 9918137, 10634130, 11505219]
African American	.29-.35	.18-.27	0	.06-.08	.06-.07	0	0	.03-.08	.15-.23	N/D	N/D	.01-.05	[Articles:9918137, 11505219, 12152006, 8098046]
Chinese	.23	.2	.01	.01	.06	N/D	N/D	.5-.7	N/D	N/D	N/D	.01	[Article:8097442]
Japanese	.42-.43	.09-.12	N/D	.01	.05-.06	N/D	N/D	.38-.41	N/D	N/D	N/D	N/D	[Articles:10886115, 10975611, 10340923]
Malay	.36	N/D	N/D	.03	.05	N/D	.03	.50	.01	N/D	N/D	N/D	[Article:11422605]
Inuit	N/D	N/D	0	.08	N/D	N/D	N/D	.02	N/D	N/D	N/D	.01	[Article:9164697]
Mexican	.57	.23	.01	.10	.02	N/D	N/D	.07	.01	N/D	N/D	.02	[Article:11753272]
Ghanaian	.44	.11	0	.07	.01	0	0	.03	.28	N/D	N/D	N/D	[Article:10634134]
Gabonese	.32	.44	N/D	N/D	.01	N/D	N/D	N/D	.24	N/D	N/D	.03	[Article:10073750]
Zimbabwean	N/D	N/D	0	.02-.03	.04	N/D	0	.06	.34	N/D	N/D	N/D	[Articles:7908586, 8911874]
Tanzanian	.28	.2	0	.01	.06	0	0	.04	.17	N/D	N/D	.14	[Articles:10634133, 11470994, 11372584]
Ethiopean	N/D	N/D	0	.01	.03	N/D	N/D	.09	.1	N/D	N/D	N/D	[Article:8764380]
Amerindian	.66	.19	0	.04-.17	.04	.01	0	.02-.18	N/D	N/D	N/D	.03	[Articles:10376769, 9731721]
Subsaharan Africa	.24	.33	0	.03	.06	0	0	.04	.12	.07	.03	.28	[Article:17301689]
North Africa	.12	.28	0	.12	.03	0	0	0	.08	0	.08	.07	[Article:17301689]
Middle Eastern	.35	.25	0	.07	.04	.01	0	.01	.02	0	.17	.02	[Article:17301689]
Europe	.34	.29	0	.17	.03	.01	.03	.03	0	0	.07	.01	[Article:17301689]
Central/South Asia	.43	.29	0	.08	.04	0	0	.04	0	0	.11	.01	[Article:17301689]
East Asia	.31	.16	0	.03	.06	0	0	.4	0	0	.02	.12	[Article:17301689]
Oceania	.72	0	0	0	.01	0	0	.03	0	0	0	.05	[Article:17301689]
Native American	.60	.30	0	.03	.01	0	0	0	.01	0	0	.05	[Article:17301689]

Key Publications:	CYP2D6 worldwide genetic variation shows high frequency of altered activity variants and no continental structure. Pharmacogenetics and genomics. 2007. Sistonen Johanna, Sajantila Antti, Lao Oscar, Corander Jukka, Barbujani Guido, Fuselli Silvia. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002. Bradford L DiAnne. Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype. Human molecular genetics. 1994. Saxena R, Shaw G L, Relling M V, Frame J N, Moir D T, Evans W E, Caporaso N, Weiffenbach B.
Drugs / Other Molecules	Drug (38) amitriptyline ¹ atomoxetine ² carvedilol ³ chlorpheniramine ⁴ chlorpromazine ⁵ citalopram ⁶ clomipramine ⁷ clozapine ⁸ codeine ⁹ debrisoquine ¹⁰ desipramine ¹¹ dextromethorphan ¹² doxepin ¹³ flecainide ¹⁴ fluoxetine ¹⁵ fluvoxamine ¹⁶ gefitinib ¹⁷ haloperidol ¹⁸ imipramine ¹⁹ maprotiline ²⁰ metoprolol ²¹ mexiletine ²² mianserin ²³ morphine ²⁴ nortriptyline ²⁵ paroxetine ²⁶ perhexiline ²⁷ perphenazine ²⁸ propafenone ²⁹ risperidone ³⁰ sparteine ³¹ tamoxifen ³² thioridazine ³³ timolol ³⁴ tolterodine ³⁵ tramadol ³⁶ yohimbine ³⁷ zuclopenthixol ³⁸
Diseases	Cystic Fibrosis Depression Hypertension Neoplasms Pain Parkinson Disease Schizophrenia

Appendix

How many SNPs, indels, repeats define this haplotype?	CYP2D6 haplotypes are typically determined by a genotyping algorithm. For the purposes of this VIP, we will define the SNPs that make up a haplotype from those SNPs which have variant pages. For fully defined CYP2D6 haplotypes, please see http://www.cypalleles.ki.se/cyp2d6.htm CYP2D6*6 includes CYP2D6 1707 del T (rs5030655)