Gene:

CYP2D6

cytochrome P450, family 2, subfamily D, polypeptide 6

Overview

Details

Introduction

View Full VIP Annotation

Introduction 
The cytochrome P450 2D6 (CYP2D6) is an enzyme of great historical importance for pharmacogenetics and is now thought to be involved in the metabolism of up to 25% of the drugs that are in common use in the clinic [18001838]. Several years before the gene was cloned, researchers observed that Caucasian subjects responded in a bimodal pattern to certain drugs such as debrisoquine and sparteine [71400, 499318], with most patients exhibiting "normal" pharmacokinetics, whereas others seemed to have great difficulty in metabolizing debrisoquine or sparteine. Debrisoquine and sparteine became examples of so-called probe drugs, and were used to phenotype patients [6644761]. This finding led researchers to conclude that there were common polymorphisms in an as yet unidentified metabolic gene that contributed to the variable pharmacokinetics of these drugs. The protein responsible for the altered metabolism was later purified from human liver microsomes by Distlerath et al. [4019462]. The gene encoding this protein was initially localized to chromosome 22 by Eichelbaum et al. [3472585]. The cDNA was cloned by Gonzalez et al. [3123997, 3410476] from human liver cDNA libraries using an antibody against the rat ortholog. The deduced human protein revealed 73% sequence similarity with the rat protein and by use of human-rodent somatic cell hybrids the gene was localized to human chromosome 22 [3410476], confirming the earlier study [3472585]. This gene came to be called CYP2D6, and is part of the cytochrome P450 gene family - a group of enzymes that is responsible for Phase I metabolism and elimination of numerous endogenous substrates and a diverse array of drugs. Among the drug-metabolizing CYPs, CYP2D6 is the only non-inducible enzyme, which results in a large contribution of genetic variation to the interindividual variation in enzyme activity [18001838]. CYP2D6 is highly polymorphic, with over 90 known allelic variants [8807658]. A selection of these variants and haplotypes is described in this summary, and the full list of all named alleles can be found at: http://www.cypalleles.ki.se/cyp2d6.htm.

CYP2D6 metabolizer classes
CYP2D6 became an object of intense research following its identification as the gene responsible for the altered activity observed with debrisoquine and other drugs. It soon became apparent that there were many different polymorphisms in all parts of the world that impacted CYP2D6 activity [17301689]. There were alleles that led to a complete loss of CYP2D6 activity, which were common in the initially studied Caucasian populations [12959412]; however, studies in populations of other ethnic origins revealed reduced function and even hyperfunctional CYP2D6 alleles [7903454, 3410476]. A system of assigned patients into four categories based on their ability to metabolize CYP2D6 substrates began to emerge. They are, listed in order of highest functioning to lowest: ultrarapid metabolizers (UM), extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM) [16968950, 14618296]. An individual's highest functioning CYP2D6 allele predicts his/her phenotypic activity [16968950, 14618296] (e.g. EM allele and PM allele results in an EM phenotype, UM allele and EM allele results in UM phenotype, IM allele and PM allele results in IM phenotype, etc.). EMs possess at least one fully functional CYP2D6 allele, and are thought of as phenotypically normal. IMs (two reduced function or one reduced and one non-functional allele) and PMs (two non-functional alleles) are not able to metabolize CYP2D6 substrates as well as their EM counterparts, and may be at increased risk for adverse effects resulting from higher plasma levels of the parent drug, or lack of efficacy resulting from an inability to form an active metabolite [16968950]. UMs, or ultrarapid metabolizers, possess multiple functional copies of a single CYP2D6 gene [12571261]. The CYP2D6 copy number has been found to be from 2-13 [12571261]. Each functional copy of CYP2D6 that is present increases the rate of metabolism of CYP2D6 substrates significantly [12571261]. CYP2D6 allele distributions exhibit significant interethnic differences. According to a review by Ingelman-Sundberg et al. [18001838], PMs are mainly found in Europe, and UMs are mainly found in North Africa and Oceania. Due to the high Asian prevalence of the CYP2D6*10 allele, IMs are located to a great extent in Asia [18001838, 15492763].

CYP2D6 substrates and therapeutic implications
CYP2D6 polymorphisms have implications across many different therapeutic areas, as a diverse array of clinically used drugs are metabolized by CYP2D6 [16968950] (see Drugs/Substrates section for references). Examples of CYP2D6 substrates can be found in antidepressants (amitriptyline, citalopram, clomipramine, desipramine, doxepin, fluvoxamine, imipramine, maprotiline, mianserin, nortriptyline, fluoxetine, paroxetine), antipsychotics (chlorpromazine, clozapine, haloperidol, perphenazine, risperidone, thioridazine, zuclopenthixol), antiarrhythmics (flecainide, mexiletine, propafenone), beta-blockers (carvedilol, metoprolol, yohimbine, timolol), opioid analgesics (codeine, dihydrocodeine, morphine, tramadol), anticancer agents (debrisoquine, gefitinib, sparteine, tamoxifen), and assorted other drugs (atomoxetine, dextromethorphan, perhexilline, tolterodine). The impact that a CYP2D6 polymorphism has on therapy with any of the aforementioned drugs is related to the resulting metabolizer status that the polymorphism(s) cause in the individual receiving therapy, as well as whether the parent drug is active or if it requires CYP2D6 to metabolize it into an active metabolite. If the parent drug is active, then UMs may suffer from a lack of efficacy whereas IMs and PMs may suffer from complications resulting from higher than desired plasma concentrations of the drug [12571261]. If the parent drug must be converted to an active metabolite in order to relieve symptoms, then IMs and PMs may be deficient in the formation of the metabolite, and therefore not receive symptomatic relief [12571261].

Phenocopying and Autophenocopying
Therapy with CYP2D6 substrates can be complex, not only due to genetic variation, but also due to drug-drug interactions. Many drugs are CYP2D6 inhibitors (such as the statins [8737761]), and taking an inhibitory drug along with a CYP2D6 substrate can alter the apparent phenotype of the patient. This phenomenon is known as phenocopying [16968950 12870705]. When this situation occurs, an EM can appear to be a IM or a PM because most of the available enzyme is being inhibited by a confounding drug. A related phenotype that can occur with chronic dosing of a CYP2D6 drug is called autophenocopying, in which a CYP2D6 substrate can inhibit its own metabolism over time as the concentration of the drug approaches steady state [16968950]. The pharmacokinetic profile of a single dose and of repeated dosing for drugs that exhibit phenocopying can therefore differ markedly [16968950].

CYP2D6 SNPs and Haplotypes 
Traditionally, allele frequency is reported with respect to an individual SNP, and haplotypes are constructed from a collection of those polymorphic sites. However, in the CYP2D6 literature, allele frequencies are usually reported in terms of haplotypes. We have therefore included the CYP2D6 allele frequency table in the haplotype section of this summary. CYP2D6 genotyping has traditionally been done according to an algorithm that appears in Gaedigk et al [10634130] in which several SNPs are tested for, and if none are found, then the algorithm defaults to either CYP2D6*1 or CYP2D6*2. We have classified the SNPs that are used to differentiate the haplotypes that we have summarized, and indicated whether that SNP has any role in the altered function when possible. Since most of the CYP2D6 literature is focused on determining an individual's metabolic status, we have chosen the haplotypes that most commonly result in altered CYP2D6 function, although many more exist. The CYP2D6 variant page should therefore serve mainly as a guide to determining the CYP2D6 haplotype, which should in turn serve as a guide to determining the metabolizer status and allele frequency.

In-Depth Annotations ()

1. rs59421388 at chr22:40853554 in CYP2D6
   This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.

   Variant Name:

   CYP2D6: 3183G>A; 3271G>A

   Related Drugs:

   citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol

   Related Diseases:

   Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp
   

2. rs28371725 at chr22:40853749 in CYP2D6
   This intronic polymorphism causes a splicing defect resulting in an activity reduction. This variant is diagnostic of the haplotype CYP2D6*41.

   Variant Name:

   CYP2D6*41; CYP2D6:2988G>A

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-999
   

3. rs16947 at chr22:40853887 in CYP2D6
   This common SNP is found in the CYP2D6*2 haplotype among others.

   Variant Name:

   CYP2D6:2850C>T

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-888
   

4. rs28371720 at chr22:40854122 in CYP2D6
   Causes deletion of amino acid, K281. Contrary to in vitro results, in vivo study has cast doubt on whether or not this variant leads to reduced function.

   Variant Name:

   CYP2D6*9; CYP2D6:2613-2615delAGA

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-777
   

5. rs4986774 at chr22:40854188 in CYP2D6
   Causes a frameshift mutation that results in a truncated, non-functional protein and is the diagnostic SNP for the CYP2D6*3 haplotype.

   Variant Name:

   CYP2D6*3; CYP2D6:2549 del A

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-666
   

6. rs3892097 at chr22:40854891 in CYP2D6
   Causes a splicing defect that results in a non-functional protein and is diagnostic for the CYP2D6*4 haplotype.

   Variant Name:

   CYP2D6*4; CYP2D6:1846G>A

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-555
   

7. rs5030655 at chr22:40855030 in CYP2D6
   Causes a frameshift mutation that results in a truncated, non-functional version of CYP2D6 and is diagnostic for the haplotype CYP2D6*6.

   Variant Name:

   CYP2D6*6; CYP2D6:1707 del T

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-444
   

8. rs61736512 at chr22:40855078 in CYP2D6
   This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.

   Variant Name:

   CYP2D6: 1659G>A; 1747G>A

   Related Drugs:

   citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol

   Related Diseases:

   Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp
   

9. rs28371706 at chr22:40855716 in CYP2D6
   Variant was identified as being part of the reduced function haplotype CYP2D6*17.

   Variant Name:

   CYP2D6:1023 C>T

   Evidence:

   http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-222
   

10. rs1065852 at chr22:40856638 in CYP2D6
    SNP is part of both the non-functional CYP2D6*4 haplotype and the reduced function CYP2D6*10 haplotype.

    Variant Name:

    CYP2D6:100C>T

    Evidence:

    http://www.pharmgkb.org/.../variant.jsp#ImportantVariantInformationforCYP2D6-111
    

Curated Annotations ()

1. rs1135840 at chr22:40852557 in CYP2D6
   This common SNP is found in the reduced function CYP2D6*10, *17, and *41 haplotypes among others.

   Variant Name:

   CYP2D6: S486T

   Evidence:

   PMID:18839161
   PMID:7935325
   PMID:8287064
   

2. rs1135840 at chr22:40852557 in CYP2D6
   Risk or phenotype-associated allele: T. Phenotype: The CYP2D6*2A haplotype was associated with lower incidence of breast cancer on tamoxifen compared to placebo in a prevention study. The CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. Study size: 182. Study population/ethnicity: Women in the Italian Tamoxifen Prevention trial, Caucasian, Italy. Significance metric(s): p = 0.0001. Type of association: CO.

   Variant Name:

   CYP2D6:4180G>C, part of CYP2D6*2A an extensive metabolizer haplotype.

   Related Drugs:

   tamoxifen

   Related Diseases:

   Breast Neoplasms

   Evidence:

   PMID:20309015
   

3. rs28371725 at chr22:40853749 in CYP2D6
   This variant is part of the CYP2D6*41 IM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.

   Variant Name:

   CYP2D6:2988G>A, part of CYP2D6*41

   Related Drugs:

   metoprolol

   Evidence:

   PMID:19037197
   http://preview.pharmgkb.org/.../variant.jsp
   

4. rs16947 at chr22:40853887 in CYP2D6
   Risk or phenotype-associated allele: T. Phenotype: The CYP2D6*2A haplotype was associated with lower incidence of breast cancer on tamoxifen compared to placebo in a prevention study. The CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. Study size: 182. Study population/ethnicity: Women in the Italian Tamoxifen Prevention trial, Caucasian, Italy. Significance metric(s): p = 0.0001. Type of association: CO.

   Variant Name:

   CYP2D6:2850C>T, part of CYP2D6*2A an extensive metabolizer haplotype.

   Related Drugs:

   tamoxifen

   Related Diseases:

   Breast Neoplasms

   Evidence:

   PMID:20309015
   

5. rs4986774 at chr22:40854188 in CYP2D6
   This variant is part of the CYP2D6*3 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.

   Variant Name:

   CYP2D6:2549 del A, part of CYP2D6*3

   Related Drugs:

   metoprolol

   Evidence:

   PMID:19037197
   http://preview.pharmgkb.org/.../variant.jsp
   

6. rs3892097 at chr22:40854891 in CYP2D6
   The variant allele CYP2D6*4 is the main polymorphism resulting in reduced enzyme activity in Caucasians. A number of studies show that poor metabolizer (PMs:*4/*4) reqiure a lower dose of drugs which get metabolized by CYP2D6.

   Variant Name:

   CYP2D6*4

   Related Drugs:

   clomipramine, codeine, desipramine, imipramine, nortriptyline, venlafaxine

   Related Diseases:

   Drug Toxicity

   Evidence:

   PMID:16958828
   PMID:1782973
   PMID:18070221
   

7. rs3892097 at chr22:40854891 in CYP2D6
   This variant is diagnostic for the non-functional CYP2D6*4 haplotype. Individuals with CYP2D6 *6/*4 , *5/*4 or *6/*6 genotypes are poor metabolizers of venlafaxine and are more prone to drug-induced side effects such as nausea, vomiting and diarrhea. However, CYP2D6 genotype does not seem to influence venlafaxine efficacy.

   Variant Name:

   CYP2D6:1846G>A

   Related Drugs:

   venlafaxine

   Related Diseases:

   Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting

   Evidence:

   PMID:16958828
   

8. rs3892097 at chr22:40854891 in CYP2D6
   This variant is diagnostic for the CYP2D6*4 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.

   Variant Name:

   CYP2D6:1846G>A, part of CYP2D6*4

   Related Drugs:

   metoprolol

   Evidence:

   PMID:19037197
   http://preview.pharmgkb.org/.../variant.jsp
   

9. rs3892097 at chr22:40854891 in CYP2D6
   In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tended to have a higher risk of disease relapse and a lower incidence of hot flashes.

   Variant Name:

   CYP2D6:1846G>A, part of CYP2D6*4

   Related Drugs:

   tamoxifen

   Evidence:

   PMID:16361630
   http://preview.pharmgkb.org/.../variant.jsp
   

10. rs3892097 at chr22:40854891 in CYP2D6
    This study of 43 patients with systemic sclerosis and 129 healthy volunteers showed higher prevalence of the CYP2D6*4 mutated alleles in patients with systemic sclerosis and the obtained OR values (OR = 2.6; P = 0.0002) suggest that this mutation has the effect of increasing systemic sclerosis morbidity rate.

    Variant Name:

    CYP2D6*4; CYP2D6:1846G>A

    Related Diseases:

    Sclerosis

    Evidence:

    PMID:19444434
    

11. rs5030655 at chr22:40855030 in CYP2D6
    This variant is the defining SNP for CYP2D6*6 and encodes a non-functional variant of CYP2D6. Individuals with CYP2D6 *6/*4 , *5/*4 or *6/*6 genotypes are poor metabolizers of venlafaxine and are more prone to drug-induced side effects such as nausea, vomiting and diarrhea. However, CYP2D6 genotype does not seem to influence venlafaxine efficacy.

    Variant Name:

    CYP2D6:1707 del T; CYP2D6*6

    Related Drugs:

    venlafaxine

    Related Diseases:

    Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting

    Evidence:

    PMID:16958828
    

12. rs5030655 at chr22:40855030 in CYP2D6
    This variant is part of the CYP2D6*6 PM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.

    Variant Name:

    CYP2D6:1707 del T, part of CYP2D6*6

    Related Drugs:

    metoprolol

    Evidence:

    PMID:19037197
    http://preview.pharmgkb.org/.../variant.jsp
    

13. rs1065852 at chr22:40856638 in CYP2D6
    This variant is part of the CYP2D6*4 PM haplotype but also part of the CYP2D6*10 IM haplotype. Plasma concentrations of metoprolol were shown to be were 4.9-fold higher in the PMs, with greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs.

    Variant Name:

    CYP2D6:100C>T, part of CYP2D6*4 and CYP2D6*10

    Related Drugs:

    metoprolol

    Evidence:

    PMID:19037197
    http://preview.pharmgkb.org/.../variant.jsp
    

Non-Curated Information

A list of non-curated publications that mention this gene along with other genes is available.

PharmGKB Curated Pathways

• Anti-estrogen Pathway (Tamoxifen PK)
• Celecoxib Pathway
• Citalopram Pathway (PK)
• Codeine and Morphine Pathway (PK)
• Gefitinib Pathway (PK)
• Imatinib Pathway
• Imipramine/Desipramine Pathway (PK)
• Selective Serotonin Reuptake Inhibitors (SSRI) Fluoxetine Pathway (PK)
• Statin Pathway (Fluvastatin PK)
• Statin Pathway (PK)

Reactome Pathways†

• P450 Dehydrogenation of alkanes to form alkenes - (Reactome via Pathway Interaction Database)
• Xenobiotics - (Reactome via Pathway Interaction Database)

Curated Information

The following drugs are in curated knowledge about this gene.

	Drug Class	Relationship	Evidence
	Anticholinesterases	CO    PK FA	Publications
	antidepressants	CO    PK    GN	Publications
	Antihypertensives	PD PK    GN	Publications
	antipsychotics	CO          GN	Publications
	Anxiolytics	GN	Publications
	Beta Blocking Agents	PK    GN	Publications
	interferons	PK	Publications
	opioids	GN	Publications
	xenobiotics	CO    PK FA GN	Publications

	Drug	Relationship	Evidence
	1-methyloxy-4-sulfone-benzene	CO          GN	Publications
	3,4-methylenedioxymethamphetamine	PD PK FA GN	Publications
	4-methylthioamphetamine	GN	Publications
	acetaminophen	CO PD PK    GN	Publications
	alprazolam	PK	Publications
	amiodarone	PK	Publications
	amitriptyline	CO    PK    GN	Publications
	amlodipine	PK	Publications
	amodiaquine	PK	Publications
	amphetamine	PK	Publications
	aripiprazole	PK    GN	Publications
	atomoxetine	PK    GN	Publications
	atorvastatin	PD PK FA GN	Publications
	azathioprine	PK    GN	Publications
	benztropine	PK	Publications
	bupropion	PD PK	Publications
	caffeine	PK	Publications
	carvedilol	PK	Publications
	celecoxib	PK	Publications
	cerivastatin	PD PK FA GN	Publications
	cetirizine	PK	Publications
	cevimeline	GN	Publications
	chloroquine	PK	Publications
	chlorpheniramine	PK	Publications
	chlorpromazine	PK	Publications
	cimetidine	PK	Publications
	cinacalcet	PK	Publications
	citalopram	CO    PK FA GN	Publications, Variants
	clemastine	PK	Publications
	clomipramine	CO PD PK    GN	Publications, Variants
	clozapine	CO    PK FA GN	Publications
	cocaine	PK	Publications
	codeine	CO PD PK FA GN	Publications, Variants
	cyclobenzaprine	PK	Publications
	cyclophosphamide	CO PD PK    GN	Publications
	cyclosporine	PK	Publications
	debrisoquine	PD PK    GN	Publications
	delavirdine	PK	Publications
	desipramine	CO    PK    GN	Publications, Variants
	desmethylcitalopram	CO	Publications
	dextromethorphan	PD PK FA GN	Publications
	diclofenac	PK	Publications
	digoxin	PK	Publications
	diltiazem	PK	Publications
	diphenhydramine	PK	Publications
	diphenylpyraline	PK	Publications
	docetaxel	CO    PK    GN	Publications
	donepezil	CO    PK    GN	Publications
	doxepin	PK    GN	Publications
	duloxetine	PK	Publications
	efavirenz	PK	Publications
	erythromycin	PK	Publications
	escitalopram	CO    PK    GN	Publications
	ethanol	PK    GN	Publications
	ezetimibe	PK	Publications
	felodipine	PK	Publications
	flavopiridol	CO PD PK    GN	Publications
	flecainide	PK	Publications
	fluoxetine	CO    PK    GN	Publications, Variants
	fluphenazine	CO PD PK	Publications
	fluvastatin	CO    PK FA GN	Publications
	fluvoxamine	CO    PK    GN	Publications, Variants
	gabapentin	PK	Publications
	galantamine	CO    PK FA	Publications
	gefitinib	PK	Publications, Variants
	glibenclamide	PK	Publications
	GS-9350	PD PK	Publications
	halofantrine	PK	Publications
	haloperidol	CO PD PK    GN	Publications, Variants
	hydrocodone	PK FA GN	Publications
	hydroxyzine	PK	Publications
	imatinib	PK	Publications
	imipramine	CO    PK    GN	Publications, Variants
	indinavir	PK	Publications
	itraconazole	PK	Publications
	ketoconazole	PK	Publications
	levomepromazine	CO	Publications
	loratadine	PK	Publications
	losartan	PK	Publications
	maprotiline	CO	Publications
	mephenytoin	PK	Publications
	mercaptopurine	PK    GN	Publications
	methadone	PD PK    GN	Publications
	metoclopramide	PK	Publications
	metoprolol	CO PD PK    GN	Publications, Variants
	mexiletine	PD PK    GN	Publications
	mianserin	CO	Publications
	midazolam	PK    GN	Publications
	mirtazapine	PD PK    GN	Publications
	morphine	CO PD PK FA GN	Publications, Variants
	naltrexone	PK    GN	Publications
	nebivolol	PD PK    GN	Publications
	nelfinavir	PK	Publications
	nevirapine	PK	Publications
	nicardipine	PK	Publications
	nifedipine	PK	Publications
	Nilotinib		Publications
	nortriptyline	CO    PK    GN	Publications, Variants
	olanzapine	CO    PK	Publications
	omeprazole	PK	Publications
	oxycodone	PK    GN	Publications
	paclitaxel	PK    GN	Publications
	paroxetine	CO    PK    GN	Publications
	perhexiline	PK	Publications
	perphenazine	CO PD PK    GN	Publications
	pimozide	PK	Publications
	pioglitazone	PK FA GN	Publications
	pravastatin	PK FA	Publications
	primaquine	FA	Publications
	promethazine	PK	Publications
	propafenone	PK	Publications
	propoxyphene	CO    PK	Publications
	propranolol	PK FA	Publications
	protriptyline	GN	Publications
	quetiapine	PK	Publications
	quinidine	PK FA	Publications
	ranitidine	PK	Publications
	reboxetine	PK	Publications
	ribavirin	PK	Publications
	rifampin	PK	Publications
	risperidone	CO PD PK    GN	Publications
	ritonavir	PK    GN	Publications
	saquinavir	PK	Publications
	sertraline	CO PD PK	Publications
	simvastatin	CO PD       GN	Publications
	sparteine	CO    PK FA GN	Publications
	tamoxifen	CO PD PK FA GN	Publications, Variants
	tamsulosin	PK	Publications
	tegafur	PK    GN	Publications
	terbinafine	PK    GN	Publications
	thalidomide	CO    PK    GN	Publications
	theophylline	PK	Publications
	thioridazine	CO    PK    GN	Publications
	thiotepa	PK	Publications
	thiothixene	PK	Publications
	ticlopidine	PK	Publications
	timolol	PK	Publications
	tiotropium	PK	Publications
	tipranavir	PK    GN	Publications
	tolbutamide	PK	Publications
	tolterodine	GN	Publications
	tramadol	CO PD PK    GN	Publications, Variants
	tranylcypromine	CO	Publications
	trazodone	PK    GN	Publications
	tripelennamine	PK	Publications
	venlafaxine	CO PD PK    GN	Publications, Variants
	verapamil	PK	Publications
	warfarin	CO PD PK	Publications
	yohimbine	PD PK    GN	Publications
	ziprasidone	PK	Publications
	zuclopenthixol	CO    PK	Publications

Non-Curated Information

A list of non-curated publications that mention this gene along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this gene.

	Disease	Relationship	Evidence
	Alzheimer Disease	CO    PK FA GN	Publications
	Anxiety Disorders	GN	Publications
	Basal Cell Nevus Syndrome	GN	Publications
	Body Weight Changes	GN	Publications
	Bradycardia	CO    PK    GN	Publications
	Breast Neoplasms	CO PD PK FA GN	Publications, Variants
	codeine dependence	CO PD PK	Publications
	Colorectal Neoplasms	CO PD PK    GN	Publications
	Cystic Fibrosis	PK	Publications, Variants
	Death	CO	Publications
	Dementia	CO    PK FA	Publications
	Dementia, Vascular	CO    PK FA	Publications
	Depression	CO PD PK    GN	Publications, Variants
	Depressive Disorder	CO    PK    GN	Publications, Variants
	Depressive Disorder, Major		Variants
	Diabetes Mellitus, Type 2	PK FA GN	Publications
	Diarrhea		Variants
	Drug interaction with drug	PK    GN	Publications
	Drug Toxicity	CO    PK FA GN	Publications, Variants
	Hepatitis C, Chronic	PK	Publications
	Hepatitis, Autoimmune		Publications
	Hypercholesterolemia	CO          GN	Publications
	Hyperlipidemias	CO          GN	Publications
	Hypertension	PD PK    GN	Publications, Variants
	Leukemia	CO PD PK    GN	Publications
	Lewy Body Disease	CO    PK FA	Publications
	Lung Neoplasms	CO PD PK FA GN	Publications
	Muscular Diseases	CO          GN	Publications
	Myalgia unspecified	CO          GN	Publications
	Myositis	CO          GN	Publications
	Nausea		Variants
	Neonatal death	CO    PK    GN	Publications
	Neoplasms	CO PD PK    GN	Publications, Variants
	Neurodegenerative Diseases	CO    PK FA	Publications
	Ovarian Neoplasms	CO PD PK FA GN	Publications
	Pain	CO PD PK    GN	Publications, Variants
	Parkinson Disease		Variants
	Parkinsonian Disorders	GN	Publications
	Prostatic Neoplasms	CO    PK    GN	Publications
	Psychotic Disorders	CO          GN	Publications
	Rhabdomyolysis	CO PD       GN	Publications
	Schizophrenia	CO PD PK FA GN	Publications, Variants
	Sclerosis	GN	Publications, Variants
	suicide	CO          GN	Publications
	tardive dyskinesia	CO PD PK    GN	Publications
	Vomiting		Variants

Non-Curated Information

A list of non-curated publications that mention this gene along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

1. Bone mineral density in tamoxifen patients

   • 
   • 
   • 
   • 
   • PD

   Submitted by David Flockhart, MD, PhD involving CYP2C9, CYP2D6, CYP3A5, ESR1, ESR2, SULT1A1, tamoxifen, and Breast Neoplasms
2. Hot flashes in tamoxifen patients

   • 
   • 
   • 
   • 
   • PD

   Submitted by David Flockhart, MD, PhD involving CYP2C9, CYP2D6, CYP3A5, ESR1, ESR2, SULT1A1, tamoxifen, and Breast Neoplasms
3. Lipid measurements in tamoxifen study

   • 
   • 
   • 
   • 
   • PD
   • GN

   Submitted by David Flockhart, MD, PhD involving CYP2D6, CYP3A5, ESR1, ESR2, NOS3, tamoxifen, and Breast Neoplasms
4. Lipid measurements in tamoxifen study - set 2

   • 
   • 
   • 
   • 
   • PD
   • PK
   • GN

   Submitted by David Flockhart, MD, PhD involving CYP2C9, CYP2D6, CYP3A5, ESR1, ESR2, SULT1A1, tamoxifen, and Breast Neoplasms
5. Meperidine N-demethylation by human CYP450 isoforms

   • 
   • 
   • 
   • 
   • FA

   Submitted by Mark J. Ratain, MD involving CYP2B6, CYP2C18, CYP2C19, CYP2C8, CYP2C9, CYP2D6, CYP3A4, CYP3A5, and meperidine
6. Metabolism of yohimbine by human CYP450 isoforms

   • 
   • 
   • 
   • 
   • FA

   Submitted by Daniel T. O'Connor, MD involving CYP2D6, CYP3A4, CYP3A5, yohimbine, and Hypertension
7. Patient responses to tamoxifen

   • 
   • 
   • 
   • 
   • PD
   • PK
   • GN

   Submitted by David Flockhart, MD, PhD involving ABCB1, CYP2C19, CYP2C9, CYP2D6, CYP3A5, ESR1, NOS3, SULT1A1, UGT1A6, tamoxifen, and Breast Neoplasms
8. Pharmacokinetics of Tamoxifen at 4 months

   • 
   • 
   • 
   • 
   • PK

   Submitted by David Flockhart, MD, PhD involving CYP2C9, CYP2D6, CYP3A5, ESR1, ESR2, SULT1A1, tamoxifen, and Breast Neoplasms
9. Thyroid binding globulin in tamoxifen patients

   • 
   • 
   • 
   • 
   • PD

   Submitted by David Flockhart, MD, PhD involving CYP2C9, CYP2D6, CYP3A5, ESR1, ESR2, SULT1A1, tamoxifen, and Breast Neoplasms

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. Genetic Variants in Selective Serotonin Reuptake Inhibitors (SSRIs) associated Adverse Events
2. Genetic Variants in Tricyclic Antidepressant associated Adverse Events
3. P450s involved in Efavirenz Metabolism

Downloads

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LinkOuts

Common Searches

• Comparative Genomics at UCSC
• Search BioCarta and KEGG Pathways at CGAP
• Search Reactome

Non-Curated Publications

A list of non-curated publications that mention this gene is available.