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Haplotype
CYP2D6 *4
part of CYP2D6 Cytochrome P450 Nomenclature DB Haplotype Set

Clinical PGx
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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 rs3892097 (CYP2D6), amitriptyline, antidepressants, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine and Depression (level 1A Dosage, Toxicity/ADR)

Level of Evidence: Level 1A
Type: Dosage, Toxicity/ADR
Variant: rs3892097
Genes: CYP2D6
Phenotypes: Depression
OMB Race: White

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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 rs3892097 (CYP2D6), tamoxifen and Breast Neoplasms (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: rs3892097
Genes: CYP2D6
Phenotypes: Breast Neoplasms
OMB Race: Mixed Population
Race Notes: mostly white (and variant is more prevalent in whites) but large study is unknown

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Clinical Annotation for CYP2D61, CYP2D610, CYP2D614, CYP2D621, CYP2D636, CYP2D64, CYP2D6*5, flecainide and Arrhythmias, Cardiac (level 2A)

Level of Evidence: Level 2A
Type: Other
Variant: *1, *10, *14, *21, *36, *4, *5
Genes: CYP2D6
Phenotypes: Arrhythmias, Cardiac
OMB Race: Asian

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D6*5, doxepin (level 2A Efficacy)

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

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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, CYP2D610, CYP2D63, CYP2D64, tolterodine (level 2A)

Level of Evidence: Level 2A
Type: Other
Variant: *1, *10, *3, *4
Genes: CYP2D6
OMB Race: Mixed Population
Race Notes: Asian, White and Unknown

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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, CYP2D617, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D641, CYP2D65, desipramine and Mental Disorders (level 2A)

Level of Evidence: Level 2A
Type: Other
Variant: *1, *10, *17, *1xN, *2, *2xN, *3, *4, *41, *5
Genes: CYP2D6
Phenotypes: Mental Disorders
OMB Race: Mixed Population
Race Notes: Asian, White and 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, CYP2D62, CYP2D63, CYP2D64, CYP2D65, atomoxetine and Attention Deficit Disorder with Hyperactivity (level 2A Efficacy, Toxicity/ADR)

Level of Evidence: Level 2A
Type: Efficacy, Toxicity/ADR
Variant: *1, *10, *2, *3, *4, *5
Genes: CYP2D6
Phenotypes: Attention Deficit Disorder with Hyperactivity
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 rs3892097 (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: rs3892097
Genes: CYP2D6
Phenotypes: Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting
OMB Race: Mixed Population

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Clinical Annotation for rs3892097 (CYP2D6), metoprolol (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs3892097
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for rs3892097 (CYP2D6), citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and Depression (level 3 Dosage)

Level of Evidence: Level 3
Type: Dosage
Variant: rs3892097
Genes: CYP2D6
Phenotypes: Depression
OMB Race: White

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Clinical Annotation for rs1065852 (CYP2D6), iloperidone and Schizophrenia (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: rs1065852
Genes: CYP2D6
Phenotypes: Schizophrenia
OMB Race: Unknown

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Clinical Annotation for rs1065852 (CYP2D6), escitalopram and Depressive Disorder, Major (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs1065852
Genes: CYP2D6
Phenotypes: Depressive Disorder, Major
OMB Race: Asian

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Clinical Annotation for CYP2D61, CYP2D63, CYP2D6*4, zuclopenthixol and Schizophrenia (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *3, *4
Genes: CYP2D6
Phenotypes: Schizophrenia
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D63, CYP2D6*4, olanzapine and Schizophrenia (level 3 Toxicity/ADR)

Level of Evidence: Level 3
Type: Toxicity/ADR
Variant: *1, *3, *4
Genes: CYP2D6
Phenotypes: Schizophrenia
OMB Race: Mixed Population
Race Notes: Asian, White, Unknown

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Clinical Annotation for CYP2D61, CYP2D63, CYP2D64, CYP2D65, timolol (level 3)

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

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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, CYP2D64, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and Depression (level 3 Dosage)

Level of Evidence: Level 3
Type: Dosage
Variant: *1, *4
Genes: CYP2D6
Phenotypes: Depression
OMB Race: White

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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, CYP2D64, vortioxetine (level 3 Metabolism/PK)

Level of Evidence: Level 3
Type: Metabolism/PK
Variant: *1, *4
Genes: CYP2D6
OMB Race: Mixed Population

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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 CYP2D61, CYP2D64, maprotiline, opipramol and Depression (level 3 Dosage, Toxicity/ADR)

Level of Evidence: Level 3
Type: Dosage, Toxicity/ADR
Variant: *1, *4
Genes: CYP2D6
Phenotypes: Depression
OMB Race: White

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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, CYP2D617, CYP2D62, CYP2D63, CYP2D64, CYP2D6*5, haloperidol and Schizophrenia (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *10, *17, *2, *3, *4, *5
Genes: CYP2D6
Phenotypes: Schizophrenia
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, CYP2D64, CYP2D6*5, tolperisone (level 3 Metabolism/PK)

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

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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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Clinical Annotation for CYP2D61, CYP2D610, CYP2D62, CYP2D64, CYP2D6*5, carvedilol and Heart Diseases (level 3)

Level of Evidence: Level 3
Type: Other
Variant: *1, *10, *2, *4, *5
Genes: CYP2D6
Phenotypes: Heart Diseases
OMB Race: Asian
Race Notes: Japanese

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Clinical Annotation for CYP2D61, CYP2D64, pimozide (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *4
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D615, CYP2D6*4, debrisoquine and dextromethorphan (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *15, *4
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D638, CYP2D64, CYP2D65, CYP2D6*9, debrisoquine (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *38, *4, *5, *9
Genes: CYP2D6
OMB Race: Unknown
Race Notes: Unknown and White

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Clinical Annotation for CYP2D620, CYP2D64, metoprolol (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *20, *4
Genes: CYP2D6
OMB Race: Unknown

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Clinical Annotation for CYP2D61, CYP2D611, CYP2D612, CYP2D64, CYP2D641, CYP2D65, CYP2D659, CYP2D662, CYP2D67, CYP2D68, sparteine (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *11, *12, *4, *41, *5, *59, *62, *7, *8
Genes: CYP2D6
OMB Race: Mixed Population
Race Notes: Unknown and White

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Clinical Annotation for CYP2D61, CYP2D6100, CYP2D6101, CYP2D613, CYP2D62, CYP2D631, CYP2D64, CYP2D65, CYP2D6*69, dextromethorphan (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *100, *101, *13, *2, *31, *4, *5, *69
Genes: CYP2D6
OMB Race: Mixed Population
Race Notes: White and Indo-Trinidadian

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Clinical Annotation for CYP2D61, CYP2D63, CYP2D636, CYP2D64, CYP2D640, CYP2D642, CYP2D64xN, CYP2D656, dextromethorphan (level 4)

Level of Evidence: Level 4
Type: Other
Variant: *1, *3, *36, *4, *40, *42, *4xN, *56
Genes: CYP2D6
OMB Race: Black or African American

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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.[42522613C>G;42524947C>T;42525132C>G;42525798G>C;42525811T>C;42525821G>T;42526694G>A]
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
rs1065852	A	G
rs28371703	T	G
rs28371704	C	T
rs28371705	C	G
rs1058164	G	C
rs3892097	T	C
rs1135840	G	C

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*4

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VIP Annotation

CYP2D6*4 [Articles:2211621, 1978251, 1978565] is a non-functional haplotype that contributes to the majority of PMs observed in Caucasian populations [Article:17301689]. This allele has achieved a very high frequency (see allele frequency table), and homozygous individuals are common [Article:17301689]. These individuals are at increased risk when compared to their EM counterparts for toxicities or lack of efficacy due to CYP2D6 inactivity [Article:16968950]. For example, in situations in which the drug that is given needs to be converted to an active metabolite before some phenotypic effect is observed (such as the conversion of codeine to morphine by CYP2D6 [Article:9352573]), individuals possesing a PM phenotype (most commonly caused by CYP2D6*4, although also caused by CYP2D6*3, CYP2D6*5, and CYP2D6*6) will face a lack of efficacy. Another potential adverse effect can result from high concentrations of parent drug that may build up in individuals who are PMs that is not seen in their EM counterparts, who are quickly able to reduce concentrations of parent drug by CYP2D6 metabolism [Articles:16958828, 16968950].

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. Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacological reviews. 2006. Gardiner Sharon J, Begg Evan J. CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. Journal of clinical pharmacy and therapeutics. 2006. Shams M E E, Arneth B, Hiemke C, Dragicevic A, Müller M J, Kaiser R, Lackner K, Härtter S. Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence. Pharmacogenetics. 1997. Tyndale R F, Droll K P, Sellers E M. The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934----A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. American journal of human genetics. 1990. Hanioka N, Kimura S, Meyer U A, Gonzalez F J. Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature. 1990. Gough A C, Miles J S, Spurr N K, Moss J E, Gaedigk A, Eichelbaum M, Wolf C R. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. The Journal of biological chemistry. 1990. Kagimoto M, Heim M, Kagimoto K, Zeugin T, Meyer U A.
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*4 includes CYP2D6 100C>T (rs1065852) and CYP2D6 1846G>A (rs3892097)