Haplotype
CYP2D6 *4 with related variants rs1065852 rs28371703 rs28371704 rs3892097

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.

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View the full haplotype translation table for CYP2D6

Variant Alelle
CYP2D6 14C>T
rs148382141
rs769258
rs28371696
rs1065852 A (differs from reference)
rs151226748
rs5030862
CYP2D6 607G>A
rs28371703 T (differs from reference)
rs28371704 C (differs from reference)
rs28371706
CYP2D6 1023C>A
rs1135821
rs1135822
rs1135823
rs375135093
CYP2D6 1693A>G
rs5030655
rs28371710
CYP2D6 1735G>C
rs1135824
rs3892097 T (differs from reference)
rs139779104
CYP2D6 1995delC
rs28371717
CYP2D6 2519A>C
rs35742686
rs5030656
rs16947
rs5030867
rs28371725
rs59421388
rs28371733
rs1135840
CYP2D6 137_138insT
CYP2D6 2853A>C
rs78482768
rs61736512
rs1080983
rs58188898
rs267608286
rs1080985
rs76210340
rs28588594
rs59099247
rs28735595
CYP2D6 -1245_-1244insGA
rs267608271
CYP2D6 -1094_-1093insA
CYP2D6 -1028T>C
rs59360719
rs1080989
CYP2D6 -750_-749delGA
rs28624811
CYP2D6 -695_-692delTGTG
rs28633410
CYP2D6 -629A>G
CYP2D6 -377A>G
rs1080993
rs72549358
rs267608313
rs138100349
rs118203758
CYP2D6 214G>C
CYP2D6 221C>A
CYP2D6 223C>G
CYP2D6 227T>C
CYP2D6 310G>T
CYP2D6 601delC
CYP2D6 746C>G
CYP2D6 843T>G
rs201377835
CYP2D6 887C>T
rs267608310
rs267608309
rs28371705
rs267608308
rs76187628
CYP2D6 1022A>T
rs78459009
rs1081003
rs267608289
rs267608306
rs67497403
rs267608305
rs374616348
rs1058164
CYP2D6 1720A>C/T
rs74962936
rs199849357
CYP2D6 1758G>T
rs5030865
rs370249680
CYP2D6 1863_1864ins(TTTCGCCCC)/1863_1864ins(TTTCGCCCC)2
rs111606937
CYP2D6 1887insTA
rs72549355
rs72549354
rs150163869
rs199535154
rs58440431
rs267608290
rs267608300
rs79738337
CYP2D6 2308G>A
CYP2D6 2470T>C
rs267608298
rs72549353
rs267608297
CYP2D6 2573_2574insC
rs148769737
rs28371718
CYP2D6 2576C>T
rs367543000
rs77913725
rs201830078
rs76015180
rs72549351
rs267608279
CYP2D6 2927_2945delGATCCTACATCCGGATGTG
rs140513104
rs79292917
rs72549349
CYP2D6 3030G>G/A
rs72549348
CYP2D6 3181A>G
CYP2D6 3198C>G
rs28371726
CYP2D6 3259_3260insGT
rs147960066
rs267608294
CYP2D6 3277T>C
rs150552908
rs75386357
rs77312092
rs1985842
rs28371729
rs267608292
rs2004511
rs28371730
rs267608322
rs116917064
rs28371732
rs267608285
rs61737947
CYP2D6 3877G>C
rs72549345
CYP2D6 3895C>T
CYP2D6 4042G>A
CYP2D6 4044C>T
rs113940699
CYP2D6 4094C>A
CYP2D6 4110C>G
rs150445731
CYP2D6 4125_4133dupGTGCCCACT
CYP2D6 4157T>G
CYP2D6 4388C>T
rs28371738
rs116390392
rs372465406
CYP2D6 Variable number of A's in the region -1258 to -1237a
CYP2D6 *2A CYP2D7 gene conversion in intron 1
CYP2D6 *2M CYP2D7 gene conversion in intron 1
CYP2D6 *4N gene conversion to CYP2D7 in exon 9
CYP2D6 *10D CYP2D7-like 3'-flanking region
CYP2D6 *13 CYP2D7/2D6 hybrid gene structure-varies depending upon exact variant(e.g. *13A1);all include 137_138insT, leading to obliteration of activity.
CYP2D6 *31 CYP2D7 gene conversion in intron 1
CYP2D6 *35B CYP2D7 conversion upstream of exon 1
CYP2D6 *36 gene conversion to CYP2D7 in exon 9
CYP2D6 *41 CYP2D7 gene conversion in intron 1
CYP2D6 *51 CYP2D7 gene conversion in intron 1
CYP2D6 *56A CYP2D7 gene conversion in intron 1
CYP2D6 *57 gene conversion to CYP2D7 in exon 9
CYP2D6 *58 CYP2D7 gene conversion in intron 1
CYP2D6 *61 CYP2D7 seq from intron 7 onwards
CYP2D6 more than 1 copy of the specified allele
CYP2D6 *63 CYP2D7 sequence from exon 8 onwards
CYP2D6 *68A CYP2D7 sequence from intron 1 onwards
CYP2D6 *68B-Similar but not identical switch region compared to CYP2D6*68A
CYP2D6 *82-CYP2D7 gene conversion in exon 2
CYP2D6 *83-gene conversion to CYP2D7 in exon 9
CYP2D6 Intron 1 conversion with CYP2D7 (214-245)

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)