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CYP2D6

From SNPedia
is agene
is mentioned by
Full namecytochrome P450, family 2, subfamily D, polypeptide 6
EntrezGene1565
PheGenI1565
VariationViewer1565
ClinVarCYP2D6
GeneCardsCYP2D6
dbSNP1565
DiseasesCYP2D6
SADR1565
HugeNav1565
CYPANCcyp2d6
wikipediaCYP2D6
googleCYP2D6
gopubmedCYP2D6
EVSCYP2D6
HEFalMpCYP2D6
MyGene2CYP2D6
23andMeCYP2D6
UniProtP10635
EnsemblENSG00000100197
OMIM124030
# SNPs302
 Max MagnitudeChromosome positionSummary
i400045242,524,244
i400138640,855,700
i400138742,526,775
i400139142,524,187
i400139242,524,696
i400139440,852,582
i400139642,526,721
i400139742,525,182
i400139840,852,565
i400140140,855,120
i400140242,526,712
i400140442,523,621
i400141242,522,678
i400141642,523,595
i400141742,523,592
i400141942,525,089
i400142342,525,073
i400142542,525,069
i400142642,524,033
i400142842,523,516
i400143242,525,036
i400143340,854,979
i400143442,523,940
i400144040,854,434
i400145442,524,946
i400145642,524,935
i400146040,855,896
i400146140,854,868
i400146742,523,855
i400146842,523,854
i400147142,523,843
i400147342,524,327
i400147442,523,302
i400147742,524,313
i400147840,854,254
i400148342,525,838
i400148642,525,823
i400148942,526,836
i400149042,523,763
i400149442,524,664
i400149542,525,280
i400149742,524,244
i400150140,855,716
rs1058164042,129,130
rs1058170042,127,928
rs1058171042,127,926
rs1058172042,127,526
rs1065569042,127,500
rs10658523.242,130,692CYP2D6 drug metabolism
rs1075944042,524,401
... further results

The wikipedia article on CYP2D6 is a good resource to learn about this gene, and includes a large table of the drugs known to be metabolized by the CYP2D6 protein. In fact, almost 25% of all drugs are metabolized by CYP2D6, including dextromethorphan (a key ingredient in products such as Nyquil), beta-blockers, antiarrhythmics, and antidepressants.

The authoritative source for defining alleles is the CYP Allele Nomenclature Committee's CYP2D6 Allele Nomenclature page, which has now been merged into the PharmVar CYP2D6 page.

In articles on CYP2D6 it is common to see the positions described within a reference sequence of the gene rather than SNP IDs or reference genome positions. The reference sequence used is M33388. The sequence starts at genome build 36.3 position 40856738 or genome build 37.1 position 42526794. It is on the reverse strand, which means that M33388 positions must be subtracted from the start position. In addition, M33388 positions from 601 to 1330 need to be decremented by 1, and positions from 1440 and up incremented by 1 before conversion. It also appears that negative positions need to be adjusted, but it isn't clear what standard is used to do so. Alleles are stated in minus orientation.

[PMID 19817501] appears to be a good survey of known effects of alleles.

Many variants of CYP2D6 are known. The main CYP2D6 alleles are the following:

CYP2D6*1 - the most common form, considered 'fully functional'; also known as wild-type, or WT
CYP2D6*2 - normal function except CYP2D6*2XN variants
CYP2D6*3 - nonfunctioning variant
CYP2D6*4 - nonfunctioning variant; the most common variant; rs3892097
CYP2D6*5 - nonfunctioning variant; consists of a complete deletion of the gene
CYP2D6*6 - nonfunctioning variant; rs5030655
CYP2D6*9 - partially functioning variant
CYP2D6*10 - partially functioning variant; rs1065852
CYP2D6*17 - partially functioning variant


[PMID 17115111] CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of Breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer. Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women.

[PMID 1782973] Codeine is ineffective at typical doses in up to 10% of Caucasians carrying two nonfunctional CYP2D6 alleles.

[PMID 16638864] SNPs in LIG4, ERCC2, and CYP2D6 genes were identified as putative markers predicting individuals at risk for complications arising from radiation therapy in Prostate cancer.

[PMID 9012401] Presents a tabulation of allele frequences and phenotypic consequences in a European population.

[PMID 18070221] CYP2D6*4 homozygotes should have lower doses of tricyclic antidepressants.

[PMID 16958828] CYP2D6 poor metabolizers (*4, *5, *6 alleles) have more side effects when taking antidepressants, in particular, venlafaxine (Effexor)

[PMID 18784654] CYP2D6*4 homozygotes taking a beta blocker like metoprolol are at 4x increased risk for bradycardia

[PMID 19541866] a paper on CYP2D6 CNV profiling in a chinese population.

In late 2004, the FDA approved the AmpliChip CYP450, a dedicated microarray test from Roche which allows the automated determination of a patient's CYP2D6 and CYP2C19 genotype.

In 2006 the FDA recommended an update in the tamoxifen label to reflect the increased risk of recurrence in breast cancer patients who are CYP2D6 poor metabolizers; a 2009 review of several studies since then mostly confirms worse clinical outcome in patients with decreased CYP2D6 metabolism and supports the notion that CYP2D6 genotype may well become a clinically relevant predictive marker.[PMID 19118028]

A more complete list of CYP2D6 variants includes:

Allele Name Code Defining Name/Change Rs# Comments Enzyme Activity Platforms
CYP2D6*1 Wild-type normal
CYP2D6*2 2850C>T, 4180G>C (but these also appear in other variants) rs16947(A) rs1135840(C) R296C, S486T; has several subvariants normal (except *2XN subvariant) 23andMe v4, Ancestry v2, Ancestry v2c, HumanOmni1Quad, 23andMe v2, Ancestry v2d; 23andMe v4, Ancestry v2c, 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*2XN 1661G>C, 2850C>T, 4180G>C with multiple copies rs16947(A) rs1135840(C) more than one copy of *2 variant in chromosome, N replaced by copy number increased 23andMe v4, Ancestry v2, Ancestry v2c, HumanOmni1Quad, 23andMe v2, Ancestry v2d; 23andMe v4, Ancestry v2c, 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*3A 2549delA rs35742686(-) 259frameshift none Ancestry v2c, Ancestry v2d
CYP2D6*3B 1749A>G, 2549delA rs1135824(G) rs35742686(-) N166D; 259frameshift none 23andMe v4, 23andMe v5, 23andMe v3, 23andMe v2; Ancestry v2c, Ancestry v2d
CYP2D6*4 1846G>A rs3892097(A) splicing defect; has several subvariants none Ancestry v2c, 23andMe v3, HumanOmni1Quad
CYP2D6*4F 1846G>A, 1858C>T rs3892097(A) i4001456(A) splicing defect, R173C none Ancestry v2c, 23andMe v3, HumanOmni1Quad; 23andMe v4, 23andMe v3, 23andMe v2
CYP2D6*4G 1846G>A, 2938C>T rs3892097(A) i4001467(A) splicing defect, P325L none Ancestry v2c, 23andMe v3, HumanOmni1Quad; 23andMe v4, 23andMe v3, 23andMe v2
CYP2D6*4H 1846G>A, 3877G>C rs3892097(A) rs28371733(C) splicing defect, E418Q none Ancestry v2c, 23andMe v3, HumanOmni1Quad; 23andMe v4, 23andMe v3, 23andMe v1, 23andMe v2
CYP2D6*5 whole-gene deletion CYP2D6 gene deleted none
CYP2D6*6 1707delT rs5030655 118frameshift none 23andMe v4, Ancestry v2, 23andMe v5, Ancestry v2c, 23andMe v3, 23andMe v1, 23andMe v2, Ancestry v2d
CYP2D6*7 2935A>C rs5030867 H324P none 23andMe v4, 23andMe v5, Ancestry v2c, 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*8 1758G>T rs5030865 G169X none 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*9 2615-2617delAAG rs5030656 K281del decreased 23andMe v4, Ancestry v2, 23andMe v5, Ancestry v2c, 23andMe v3, 23andMe v1, 23andMe v2, Ancestry v2d
CYP2D6*10 100C>T (but also appears in other variants) rs1065852 P34S decreased 23andMe v4, Ancestry v2c, 23andMe v3, HumanOmni1Quad, 23andMe v2
CYP2D6*11 883G>C rs5030863 none
CYP2D6*12 124G>A rs5030862 G42R none 23andMe v4, Ancestry v2, 23andMe v5, Ancestry v2c, 23andMe v3, HumanOmni1Quad, 23andMe v2, Illumina Human 1M, Ancestry v2d
CYP2D6*14 1758G>A rs5030865 G169R none 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*15 137insT; 137_138insT in-del; 46 frameshift none
CYP2D6*17 1023C>T, 2850C>T (but also appear in other variants) rs28371706(T) rs16947(A) T107I, R296C decreased FamilyTreeDNA, 23andMe v4, Ancestry v2, Ancestry v2c, 23andMe v3, FTDNA2, 23andMe v1, 23andMe v2, Ancestry v2d; 23andMe v4, Ancestry v2, Ancestry v2c, HumanOmni1Quad, 23andMe v2, Ancestry v2d
CYP2D6*18 4133dupGTGCCCACT 468_470dupVPT none
CYP2D6*19 2539_2542delAACT 255frameshift none
CYP2D6*20 1973_1974insG rs72549354(C) 211frameshift none Ancestry v2, Ancestry v2c, Ancestry v2d
CYP2D6*21 2573insC none
CYP2D6*29 1659G>A; 1661G>C; 2850C>T; 3183G>A; 4180G>C rs61736512(T) rs1058164(C) rs16947(A) rs59421388(T) rs1135840(C) V136M; R296C; V338M; S486T decreased
CYP2D6*38 2587_2590delGACT 271Frameshift none
CYP2D6*39 1661G>C, 4180G>C rs1135840 S486T normal 23andMe v4, Ancestry v2c, 23andMe v3, 23andMe v2, Ancestry v2d
CYP2D6*40 1863_1864ins(TTT CGC CCC)2 174_175ins(FRP)2 none
CYP2D6*41 2988G>A rs28371725 aberrant splicing decreased 23andMe v4, 23andMe v5, Ancestry v2c, 23andMe v3, HumanOmni1Quad, 23andMe v2, Ancestry v2d
CYP2D6*42 3259insGT; 3259_3260insGT 365frameshift none
CYP2D6*44 2950G>C splicing defect none
CYP2D6*52 3877G>A rs28371733(A) E418K possibly decreased 23andMe v4, 23andMe v3, 23andMe v1, 23andMe v2
CYP2D6*56 3201C>T R344X none
CYP2D6*1xN whole-gene duplication Nx active genes increased
CYP2D6*4xN whole-gene duplication (+1846G>A) Nx inactive genes none
CYP2D6*10xN whole-gene duplication (+100C>T) Nx decreased-activity genes decreased
CYP2D6*41xN whole-gene duplication (+2988G>A) Nx decreased- activity genes decreased
CYP2D6_(rs1080983) rs1080983 23andMe v4, 23andMe v5, 23andMe v3, 23andMe v1, 23andMe v2
CYP2D6_(rs28360521) rs28360521

source1 and source2

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