CYP2D6

From SNPedia

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.

[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 - almost fully functioning variant; rs16947
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	and(rs16947(C),rs1135840(T))	2850C>T, 4180G>C	rs16947(C) + rs1135840	R296C + S486T	normal	23andMe v2, HumanOmni1Quad;
CYP2D6*2A			rs1080985		normal	23andMe v1, 23andMe v2
CYP2D6*3		2549delA	rs35742686	frameshift; R259-	none
CYP2D6*4		1846G>A	rs3892097	splicing defect	none	HumanOmni1Quad
CYP2D6*5		whole-gene deletion		CYP2D6 gene deleted	none
CYP2D6*6		1707delT	rs5030655	118frameshift	none	23andMe v1, 23andMe v2
CYP2D6*7		2935A>C	rs5030867	H324P	none	23andMe v2
CYP2D6*8		1758G>T	rs5030865	G169X	none	23andMe v2
CYP2D6*9		2615-2617delAAG	rs5030656	K281del	decreased	23andMe v1, 23andMe v2
CYP2D6*10		100C>T	rs1065852	P34S	decreased	23andMe v2, HumanOmni1Quad
CYP2D6*11		883G>C	rs5030863		none
CYP2D6*12		124G>A	rs5030862	G42R	none	23andMe v2, HumanOmni1Quad, Illumina Human 1M
CYP2D6*14		1758G>A		G169R	none
CYP2D6*15		137insT; 137_138insT		in-del; 46 frameshift	none
CYP2D6*17		1023C>T	rs28371706	T107I	decreased	23andMe v1, 23andMe v2
CYP2D6*18		4133dupGTGCCCACT		468_470dupVPT	none
CYP2D6*19		2539_2542delAACT		255Frameshift	none
CYP2D6*20		1973insG			none
CYP2D6*21		2573insC			none
CYP2D6*29		1659G>A; 1661G>C; 2850C>T; 3183G>A; 4180G>C		V136M; R296C; V338M; S486T	decreased
CYP2D6*38		2587_2590delGACT		271Frameshift	none
CYP2D6*39		1661G>C, 4180G>C	rs1135840	S486T	normal	23andMe v2
CYP2D6*40		1863_1864ins(TTT CGC CCC)2		174_175ins(FRP)2	none
CYP2D6*41		2988G>A	rs28371725	aberrant splicing	decreased	23andMe v2, HumanOmni1Quad
CYP2D6*42		3259insGT; 3259_3260insGT		365frameshift	none
CYP2D6*44		2950G>C		splicing defect	none
CYP2D6*56		3201C>T		R344X	none
CYP2D6*1xN		whole-gene duplication		Nx active genes	increased
CYP2D6*2xN		whole-gene duplication (+2850C>T, 4180G>C)		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 v1, 23andMe v2
CYP2D6_(rs28360521)			rs28360521

source1 and source2