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.
|CYP2D6 Copy Number Variation||1|
|rs1065852||A (differs from reference)|
|rs28371703||T (differs from reference)|
|rs28371704||C (differs from reference)|
|rs28371705||C (differs from reference)|
|rs1058164||G (differs from reference)|
|rs3892097||T (differs from reference)|
|rs1135840||G (differs from reference)|
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.
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] |
|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] |
|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] |
|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]|
| 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]|
| Native American ||.60||.30||0||.03||.01||0||0||0||.01||0||0||.05||[Article:17301689]|