CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CYP2D6provided by HGNC
Official Full Name: cytochrome P450, family 2, subfamily D, polypeptide 6provided by HGNC
Primary source: HGNC:2625
Locus tag: RP4-669P10.2
See related: Ensembl:ENSG00000100197; HPRD:00487; MIM:124030; Vega:OTTHUMG00000150918
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPD6; CYP2D; CYP2DL1; CYPIID6; P450C2D; P450DB1; CYP2D7AP; CYP2D7BP; CYP2D7P2; CYP2D8P2; P450-DB1
Summary: 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 20% of commonly prescribed drugs. Its substrates include debrisoquine, an adrenergic-blocking drug; sparteine and propafenone, both anti-arrythmic drugs; and amitryptiline, an anti-depressant. The gene is highly polymorphic in the population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 22q13.1

Sequence :: Chromosome: 22; NC_000022.10 (42522501..42526883, complement)

See CYP2D6 in Epigenomics, MapViewer

Chromosome 22 - NC_000022.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Report effect of CYP2D6 inhibition on iloperidone-induced alterations of QT interval.
Title: A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone.
Post-menopause breast cancer patients with homozygous CYP2D6*10 and who are intermediate metabolizers have shorter disease-free survival.
Title: Impact of CYP2D6 polymorphisms on tamoxifen responses of women with breast cancer: a microarray-based study in Thailand.
There was a positive association between CYP2D6 heterozygote (GC) of rs1135840 and cancer risk.
Title: Genetic variants of CYP2D6 gene and cancer risk: a HuGE systematic review and meta-analysis.
Report inter-individual variability of in vivo CYP2D6 activity in different genotypes.
Title: Inter-individual variability of in vivo CYP2D6 activity in different genotypes.
Coadministration of tramadol and serotonin reuptake inhibitors has caused serotonin syndrome; CYP2D6 poor metabolizers are at a greater risk of serotonin syndrome and an inadequate analgesic effect.
Title: Avoiding serotonin syndrome: the nature of the interaction between tramadol and selective serotonin reuptake inhibitors.
A 1-compartment mixture model described risperidone and (+/-)-9-hydroxyrisperidone clearances for 3 CYP2D6 metabolizer subpopulations.
Title: Population pharmacokinetic modeling of risperidone and 9-hydroxyrisperidone to estimate CYP2D6 subpopulations in children and adolescents.
AD patients with mutant allele (*10) in CYP2D6 gene may respond better to donepezil than those with wild allele (*1). We did not find the relationship between APOE [Latin Small Letter Open E]4 status and the efficacy of donepezil in our study.
Title: Effect of CYP2D6*10 and APOE polymorphisms on the efficacy of donepezil in patients with Alzheimer's disease.
dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine
Title: Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease.
The CYP2D6*10/*10 genotype has a significant impact on the plasma exposure of tamsulosin in healthy Koreans
Title: Tamsulosin exposure is significantly increased by the CYP2D6*10/*10 genotype.
The allelic distributions of the CYP2D6 gene among Jordanians are different from other Mediterranean groups, especially the *10 and *17 single-nucleotide polymorphisms, and the CYP2D6*2xN duplication allele.
Title: Frequency of certain single-nucleotide polymorphisms and duplication of CYP2D6 in the Jordanian population.

Submit: New GeneRIF Correction See all (340)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Disorder due cytochrome p450 CYP2D6 variant

MIM: 608902

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with (+/-)fluoxetine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with (+/-)norfluoxetine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (S)-methadone.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (R)-methadone.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with Dextromethorphan.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with MPPP.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with PEPAP.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with Meperidine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (d,l)-4-Hydroxymethamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (d,l)-Cathinone.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with PMA.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (+)-Methamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (+)-Amphetamine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with 2,4,6-TMA.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with 3,4,5-TMA.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (+)-4-Hydroxyamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Codeine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Budipine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Debrisoquine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Sparteine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Amitriptyline.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with MPTP.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with (-)Methamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6.1 interacts with Paroxetine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with NOC.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with OXY.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with MMDA-2.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with BUP.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with Nor-BUP.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (d,l)-3-Methoxyamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with (d,l)-2-Methoxyamphetamine.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with MMDA
NP_000097.2			BIND	PubMed	CYP2D6 interacts with MDA.
NP_000097.2			BIND	PubMed	CYP2D6 interacts with MDMA.
BioGRID:107940	BioGRID:107908	CYB5A	BioGRID	PubMed	Reconstituted Complex
BioGRID:107940	BioGRID:107937	CYP2C9	BioGRID	PubMed	Reconstituted Complex
BioGRID:107940	BioGRID:111443	POR	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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Biological oxidations, organism-specific biosystem (from REACTOME)
Biological oxidations, organism-specific biosystemAll organisms are constantly exposed to foreign chemicals every day. These can be man-made (drugs, industrial chemicals) or natural (alkaloids, toxins from plants and animals). Uptake is usually via ...
CYP2E1 reactions, organism-specific biosystem (from REACTOME)
CYP2E1 reactions, organism-specific biosystemCYP2E1 can metabolize and activate a large number of solvents and industrial monomers as well as drugs. This quality of CYP2E1 may make it an important determinant of human susceptibility to the toxi...
Codeine and morphine metabolism, organism-specific biosystem (from WikiPathways)
Codeine and morphine metabolism, organism-specific biosystemThe principal pathways for metabolism of codeine occur in the liver, although some metabolism occurs in the intestine and brain. Approximately 50-70% of codeine is converted to codeine-6-glucuronide ...
Cytochrome P450 - arranged by substrate type, organism-specific biosystem (from REACTOME)
Cytochrome P450 - arranged by substrate type, organism-specific biosystemThe P450 isozyme system is the major phase 1 biotransforming system in man, accounting for more than 90% of drug biotransformations. This system has huge catalytic versatility and a broad substrate s...
Drug metabolism - cytochrome P450, organism-specific biosystem (from KEGG)
Drug metabolism - cytochrome P450, organism-specific biosystem
Drug metabolism - cytochrome P450
Drug metabolism - cytochrome P450, conserved biosystem (from KEGG)
Drug metabolism - cytochrome P450, conserved biosystem
Drug metabolism - cytochrome P450
Fatty Acid Omega Oxidation, organism-specific biosystem (from WikiPathways)
Fatty Acid Omega Oxidation, organism-specific biosystem
Fatty Acid Omega Oxidation
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, organism-specific biosystem
Metabolism of xenobiotics by cytochrome P450
Metabolism of xenobiotics by cytochrome P450, conserved biosystem (from KEGG)
Metabolism of xenobiotics by cytochrome P450, conserved biosystem
Metabolism of xenobiotics by cytochrome P450
Phase 1 - Functionalization of compounds, organism-specific biosystem (from REACTOME)
Phase 1 - Functionalization of compounds, organism-specific biosystemPhase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. This provides a 'handle' for phase 2 conj...
Serotonergic synapse, organism-specific biosystem (from KEGG)
Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
Tamoxifen metabolism, organism-specific biosystem (from WikiPathways)
Tamoxifen metabolism, organism-specific biosystem
Tamoxifen metabolism
Xenobiotics, organism-specific biosystem (from REACTOME)
Xenobiotics, organism-specific biosystemOf the 50 microsomal CYPs, 15 act on xenobiotics. They all possess wide substrate specificity to cater for most foreign compounds that find their way into the body.
cytochrome P450, organism-specific biosystem (from WikiPathways)
cytochrome P450, organism-specific biosystemOxidation of a substrate by Cytochrome P450. Adapted from Niesink et al., Chapter 3, p. 47-48.
metapathway biotransformation, organism-specific biosystem (from WikiPathways)
metapathway biotransformation, organism-specific biosystem
metapathway biotransformation

General gene information

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Markers

GDB:632773 (e-PCR)
- UniSTS:158487

GDB:632777 (e-PCR)
- UniSTS:158488

GDB:632780 (e-PCR)
- UniSTS:158489

GDB:632785 (e-PCR)
- UniSTS:158490

GDB:632790 (e-PCR)
- UniSTS:158491

GDB:632800 (e-PCR)
- UniSTS:158493

STS-M33189 (e-PCR)
- UniSTS:10271

PMC156606P1 (e-PCR)
- UniSTS:271408

GDB:222783 (e-PCR)
- UniSTS:156236

NoName (e-PCR)
- UniSTS:486996

RH27796 (e-PCR)
- UniSTS:87699

GDB:187815 (e-PCR)
- UniSTS:155569

GDB:187817 (e-PCR)
- UniSTS:155570

GDB:270292 (e-PCR)
- UniSTS:156348

NoName (e-PCR)
- UniSTS:482281

Genotypes

See CYP2D6 SNP Geneview Report
See CYP2D6 SNP Genotype Report
See CYP2D6 SNP Variation Viewer Report

Homology

Homologs of the CYP2D6 gene: The CYP2D6 gene is conserved in chimpanzee, Rhesus monkey, mouse, and rat.
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
aromatase activity	IEA Inferred from Electronic Annotation more info
drug binding	IDA Inferred from Direct Assay more info	PubMed
electron carrier activity	IEA Inferred from Electronic Annotation more info
heme binding	IDA Inferred from Direct Assay more info	PubMed
iron ion binding	IEA Inferred from Electronic Annotation more info
monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
alkaloid catabolic process	IDA Inferred from Direct Assay more info	PubMed
alkaloid metabolic process	IDA Inferred from Direct Assay more info	PubMed
coumarin metabolic process	IDA Inferred from Direct Assay more info	PubMed
drug catabolic process	IDA Inferred from Direct Assay more info	PubMed
drug metabolic process	IDA Inferred from Direct Assay more info	PubMed
drug metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
heterocycle metabolic process	IDA Inferred from Direct Assay more info	PubMed
isoquinoline alkaloid metabolic process	IDA Inferred from Direct Assay more info	PubMed
monoterpenoid metabolic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of binding	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cellular organofluorine metabolic process	IDA Inferred from Direct Assay more info	PubMed
oxidation-reduction process	IDA Inferred from Direct Assay more info	PubMed
oxidative demethylation	IDA Inferred from Direct Assay more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
steroid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
xenobiotic metabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cytochrome P450 2D6

Names: cytochrome P450 2D6; cytochrome P450-DB1; microsomal monooxygenase; xenobiotic monooxygenase; debrisoquine 4-hydroxylase; flavoprotein-linked monooxygenase; cytochrome P450, family 2, subfamily D, polypeptide 7 pseudogene 2; cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 2; cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing)-like 1; cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing), polypeptide 6; cytochrome P450, subfamily II (debrisoquine, sparteine, etc., -metabolising), polypeptide 7 pseudogene 2; cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolising), polypeptide 8 pseudogene 2

NP_000097.3

EC 1.14.14.1

NP_001020332.2

EC 1.14.14.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000106.5 → NP_000097.3 cytochrome P450 2D6 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AY663390, BC075023, CB124853

Consensus CDS

CCDS46721.1

UniProtKB/TrEMBL

C1ID52

UniProtKB/Swiss-Prot

P10635

UniProtKB/TrEMBL

Q5Y7H2

Related

ENSP00000353820, OTTHUMP00000198705, ENST00000360608, OTTHUMT00000320525

Conserved Domains (2) summary

pfam00067
Location:58 – 493
Blast Score: 1108

p450; Cytochrome P450

cl12078
Location:61 – 472
Blast Score: 446

CypX; Cytochrome P450 [Secondary metabolites biosynthesis, transport, and catabolism]
NM_001025161.2 → NP_001020332.2 cytochrome P450 2D6 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the CDS, as compared to variant 1, which results in a shorter isoform (2).

Source sequence(s)

AY663390, BC066877, BC075023, CB124853

Consensus CDS

CCDS33657.1

UniProtKB/Swiss-Prot

P10635

UniProtKB/TrEMBL

Q5Y7H2

Related

ENSP00000351927, OTTHUMP00000198706, ENST00000359033, OTTHUMT00000320526

Conserved Domains (2) summary

pfam00067
Location:58 – 442
Blast Score: 942

p450; Cytochrome P450

cl12078
Location:126 – 421
Blast Score: 386

CypX; Cytochrome P450 [Secondary metabolites biosynthesis, transport, and catabolism]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000022.10 Reference GRCh37.p10 Primary Assembly

Range

42522501..42526883, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000154.1 Alternate HuRef

Range

25488519..25492901, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018933.1 Alternate CHM1_1.0

Range

26438416..26442798, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01055663.1 (1397..5779)	None
genomic	AMYH01012810.1 (1073..5455)	None
genomic	AY545216.1	AAS55001.1
genomic	BX247885.11 (5983..10365)	None
genomic	CH471095.1	EAW60492.1
		EAW60493.1
genomic	DQ211353.1	ABB01370.1
		ABB01371.1
genomic	DQ211354.1	ABB01372.1
genomic	DQ211355.1	ABB01373.1
genomic	DQ282144.1	ABB77895.1
genomic	DQ282145.1	ABB77896.1
genomic	DQ282146.1	ABB77897.1
genomic	DQ282147.1	ABB77898.1
genomic	DQ282151.1	ABB77899.1
genomic	DQ282152.1	ABB77900.1
genomic	DQ282153.1	ABB77901.1
genomic	DQ282154.1	ABB77902.1
genomic	DQ282155.1	ABB77903.1
genomic	DQ282156.1	ABB77904.1
genomic	DQ282157.1	ABB77905.1
genomic	DQ282158.1	ABB77906.1
genomic	DQ282159.1	ABB77907.1
genomic	DQ282160.1	ABB77908.1
genomic	DQ282162.1	ABB77909.1
genomic	M33189.1	AAA35737.1
genomic	M33388.1	AAA53500.1
mRNA	AK308211.1	None
mRNA	AK309600.1	None
mRNA	AY663390.1	AAU87043.1
mRNA	BC066877.1	AAH66877.1
mRNA	BC067432.1	AAH67432.1
mRNA	BC075023.2	AAH75023.1
mRNA	BC075024.2	AAH75024.1
mRNA	BC106757.1	AAI06758.1
mRNA	BC106758.1	AAI06759.1
mRNA	BC126858.1	AAI26859.1
mRNA	BX096000.1	None
mRNA	BX422592.2	None
mRNA	CB124853.1	None
mRNA	CK032845.1	None
mRNA	CR456430.1	CAG30316.1
mRNA	M20403.1	AAA52153.1
mRNA	M24499.1	AAA36403.1
mRNA	X07618.1	None
mRNA	X08006.1	CAA30807.1
mRNA	X16865.1	None
mRNA	X16866.1	None
mRNA	AB209492.1	BAD92729.1
other-genetic	CU013213.1	CAK54644.1
other-genetic	CU013501.1	CAK54943.1