Haplotype
CYP2D6 *4 with related variants rs1065852 rs28371703 rs28371704 rs3892097 rs1135840 CYP2D6 997C>G CYP2D6 1661G>C

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.

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.

? = Mouse-over for quick help

View the full haplotype translation table for CYP2D6

Variant Alelle
rs769258 C
rs28371696 C
rs1065852 A (differs from reference)
rs5030862 C
rs28371703 T (differs from reference)
rs28371704 C (differs from reference)
rs28371706 G
rs1135822 A
rs1135823 C
rs5030655 A
rs28371710 C
rs1135824 T
rs3892097 T (differs from reference)
rs5030866 C
rs28371717 C
rs35742686 T
rs5030656 CTT
rs16947 G
rs5030867 T
rs28371725 C
rs59421388 C
rs28371733 C
rs1135840 G (differs from reference)
rs72549357 NO ins
CYP2D6 2853A>C T
rs78482768 G
rs61736512 C
CYP2D6 -1770 G>A C
CYP2D6 '-1601_-1600GA>TT TC
CYP2D6 -1584C>G G
CYP2D6 -1543 G>A C
CYP2D6 '-1426C>T G
CYP2D6 -1298G>A C
CYP2D6 -1258_-1257insAAAAA NO ins
CYP2D6 -1253A>G T
CYP2D6 -1245_-1244insGA NO ins
CYP2D6 -1238_-1237delAA NO del
CYP2D6 -1237_-1236insAA NO ins
CYP2D6 -1235A>G T
CYP2D6 -1094_-1093insA NO ins
CYP2D6 -1028T>C A
CYP2D6 -1011T>C A
CYP2D6 -1000G>A C
CYP2D6 -750_-749delGA NO del
CYP2D6 -740C>T G
CYP2D6 -695_-692delTGTG NO del
CYP2D6 -678G>A C
CYP2D6 -629A>G T
CYP2D6 -377A>G T
CYP2D6 '-175G>A C
CYP2D6 19G>A C
CYP2D6 73C>T G
CYP2D6 82C>T G
CYP2D6 125G>A C
CYP2D6 214G>C C
CYP2D6 221C>A G
CYP2D6 223C>G G
CYP2D6 227T>C A
CYP2D6 310G>T C
CYP2D6 601delC NO del
CYP2D6 746C>G G
CYP2D6 843T>G A
CYP2D6 883G>C C
CYP2D6 887C>T G
CYP2D6 957C>T G
CYP2D6 972C>T G
CYP2D6 997C>G C (differs from reference)
CYP2D6 1013G>A C
CYP2D6 1039C>T G
CYP2D6 1062A>G T
CYP2D6 1494T>C A
CYP2D6 1513C>T G
CYP2D6 1598A>G T
CYP2D6 1608G>A C
CYP2D6 1661G>C G (differs from reference)
CYP2D6 1720A>C T
CYP2D6 1724C>T G
CYP2D6 1757C>T G
rs5030865 C
CYP2D6 1858C>T G
CYP2D6 1863_1864ins(TTTCGCCCC) NO ins
CYP2D6 1863_1864ins(TTTCGCCCC)2 NO ins
CYP2D6 1869T>C A
CYP2D6 1887insTA NO ins
CYP2D6 1943G>A C
CYP2D6 1973_1974insG NO ins
CYP2D6 1978C>T G
CYP2D6 1979T>C A
CYP2D6 2097A>G T
CYP2D6 2129A>C T
CYP2D6 2291G>A C
CYP2D6 2303C>T G
CYP2D6 2470T>C A
CYP2D6 2480C>T G
CYP2D6 2539_2542delAACT NO del
CYP2D6 2556C>T G
CYP2D6 2573_2574insC NO ins
CYP2D6 2575C>A G
CYP2D6 2661G>A C
CYP2D6 2587_2590delGACT NO del
CYP2D6 2938C>T G
CYP2D6 2939G>A C
CYP2D6 2950G>C C
CYP2D6 3030G>G/A C
CYP2D6 3172A>C T
CYP2D6 3198C>G G
CYP2D6 3254T>C A
CYP2D6 3259_3260insGT NO ins
CYP2D6 3201C>T G
CYP2D6 3277T>C A
CYP2D6 3288G>A C
CYP2D6 3318G>A C
CYP2D6 3384A>C T
CYP2D6 3491G>A C
CYP2D6 3582A>G T
CYP2D6 3584G>A C
CYP2D6 3609G>T C
CYP2D6 3790C>T G
CYP2D6 3828G>A C
CYP2D6 3835A>C T
CYP2D6 3853G>A C
CYP2D6 3877G>C C
CYP2D6 3887T>C A
CYP2D6 4042G>A C
CYP2D6 4044C>T G
CYP2D6 4045G>A C
CYP2D6 4115C>T G
CYP2D6 4125_4133dupGTGCCCACT NO DUP
CYP2D6 4388C>T G
CYP2D6 4401C>T G
CYP2D6 4481G>A C
CYP2D6 4535insT NO ins
CYP2D6 *2A CYP2D7 gene conversion in intron 1 NO
CYP2D6 *2M CYP2D7 gene conversion in intron 1 NO
CYP2D6 *4N gene conversion to CYP2D7 in exon 9 NO
CYP2D6 *10D CYP2D7-like 3'-flanking region NO
CYP2D6 *13 CYP2D7/2D6 hybrid gene structure NO
CYP2D6 *14B/*21B -intron 1 conversion with CYP2D7 (214-245) NO
CYP2D6 *31 CYP2D7 gene conversion in intron 1 NO
CYP2D6 *35B CYP2D7 conversion upstream of exon 1 NO
CYP2D6 *36 gene conversion to CYP2D7 in exon 9 NO
CYP2D6 *41 CYP2D7 gene conversion in intron 1 NO
CYP2D6 *51 CYP2D7 gene conversion in intron 1 NO
CYP2D6 *56A CYP2D7 gene conversion in intron 1 NO
CYP2D6 *57 gene conversion to CYP2D7 in exon 9 NO
CYP2D6 *58 CYP2D7 gene conversion in intron 1 NO
CYP2D6 *61 CYP2D7 seq from intron 7 onwards NO
CYP2D6 *63/*73(are these the same?) intron 1 conversion with CYP2D7 (214-245) NO
CYP2D6 more than 1 copy, unspecified - active genes NO
CYP2D6 more than 1 copy: (N=2, 3, 4, 5 or 13) NO
CYP2D6 *63 CYP2D7 sequence from exon 8 onwards NO

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.

There are direct annotations for this haplotype. Register or sign in to see them.

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]
Drugs / Other Molecules
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)