CYP2D6 rs72549306: Understanding the *6 Non-Functional Allele
The rs72549306 variant is a specific genetic marker within the CYP2D6 gene that defines the non-functional *6 allele. This variant is associated with a reduced or absent ability to metabolize certain medications, which can influence how individuals respond to common drugs like codeine and tamoxifen.
What each genotype means
Normal enzyme activity
This genotype indicates the presence of two functional copies of the CYP2D6 gene at this position. Individuals with this profile are typically classified as normal metabolizers for drugs processed by this enzyme, such as certain antidepressants and analgesics. Please discuss any medication dosing or concerns with your clinician or pharmacist.
This is the most common genotype in most global populations, carried by the vast majority of individuals.
Reduced enzyme activity
This genotype includes one copy of the non-functional CYP2D6*6 allele, which contains a single nucleotide deletion that disrupts normal enzyme production. Carriers may experience reduced metabolism of specific medications, potentially leading to altered drug levels in the blood. Please consult your healthcare provider or pharmacist regarding how this may influence your response to specific prescriptions.
This genotype is observed at a low frequency, primarily in European populations, and is considered rare in East Asian and African populations.
Absent enzyme activity
This genotype indicates that both copies of the gene carry the non-functional CYP2D6*6 variant, which prevents the production of a working CYP2D6 enzyme. This status is associated with a poor metabolizer phenotype, meaning the body may not process certain drugs effectively, which can impact therapeutic outcomes. It is important to discuss this genetic finding with your clinician or pharmacist before starting any new medication.
This homozygous genotype is very rare across all major global populations due to the low frequency of the T allele.
What is rs72549306?
The rs72549306 variant is a single nucleotide deletion, specifically a thymine deletion (c.1707delT), located within the CYP2D6 gene. In genetic nomenclature, this specific change is responsible for defining the CYP2D6*6 allele. Because this deletion occurs in the coding sequence of the gene, it causes a frameshift mutation. A frameshift mutation alters the reading frame of the genetic code, typically resulting in a non-functional or truncated protein product. Consequently, the enzyme produced by this allele is unable to perform its normal metabolic functions. This variant is categorized under pharmacogenomics, a field of study that examines how an individual's genetic makeup influences their response to drugs. Understanding such variants is essential for identifying why some people may experience different therapeutic outcomes or side effects when taking medications that rely on this specific enzyme pathway.
The Role of the CYP2D6 Gene
The CYP2D6 gene provides instructions for making an enzyme called cytochrome P450 2D6. This enzyme is primarily produced in the liver and is responsible for the metabolism of approximately 20% to 25% of all clinically used drugs. It acts as a biological catalyst, helping the body break down or activate substances such as antidepressants, neuroleptics, beta-blockers, and pain medications like codeine. Because CYP2D6 is highly polymorphic—meaning it has many different variations across the human population—the activity levels of this enzyme can vary significantly between individuals. Some people have highly active enzymes, while others have reduced or completely absent activity. When a person carries non-functional alleles like the one defined by rs72549306, their ability to process these medications is impaired. This can lead to either a lack of therapeutic effect if the drug requires activation, or an accumulation of the drug in the body, which may increase the risk of adverse side effects.
Research and Clinical Significance
Research into rs72549306 and the *6 allele is categorized as having limited evidence compared to more common variants, though it is well-documented as a non-functional allele. Clinical pharmacogenetics guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC), emphasize the importance of identifying non-functional alleles to optimize drug therapy. For medications like tamoxifen, which requires conversion by CYP2D6 to its active form, or codeine, which is metabolized into morphine, the presence of non-functional alleles can be clinically significant. However, it is important to note that the clinical impact of any single variant depends on the individual's full genotype, including the status of both copies of the gene. Because evidence for this specific variant is limited, it is not always included in standard, broad-spectrum screening panels. Patients should always consult with their clinician or pharmacist to interpret how their specific genetic results might influence their medication management and to discuss appropriate dosing strategies.
Population Frequency
The frequency of the rs72549306 variant varies significantly across different ancestral groups. In European populations, the minor allele frequency is approximately 0.01, making it an uncommon but identifiable variant. In contrast, the variant is considered rare in East Asian and African populations, with frequencies typically reported at less than 0.001. These differences highlight the importance of considering ancestry when evaluating pharmacogenetic risks. Because the variant is relatively rare, it is not a primary driver of population-wide drug response differences in the same way that more common variants like *10 or *4 are. Nevertheless, for individuals who do carry this variant, the functional impact on drug metabolism remains consistent regardless of their background. Genetic testing reports often provide context on how these frequencies compare to the general population, but clinical decisions should always be based on an individual's specific genotype rather than population averages.
What You Can Do With This Information
If you have received information about your rs72549306 status, it is important to view it as one piece of a larger clinical puzzle. You cannot use this information to diagnose yourself or make changes to your medication regimen. Pharmacogenomics is complex, and drug response is influenced by many factors, including age, liver function, other medications you may be taking, and your overall health. If you are concerned about how your genetics might affect your response to a specific drug, the best course of action is to share your genetic report with your doctor or a clinical pharmacist. They are trained to interpret these results in the context of your medical history and can determine if a dosage adjustment or an alternative medication is appropriate. Never stop or change the dose of a prescribed medication based on genetic test results without professional medical guidance, as doing so could be harmful to your health.
How common is this variant?
The rs72549306 variant has a minor allele frequency of approximately 0.01 in European populations and is rare (<0.001) in East Asian and African populations.
Frequently asked questions
What does it mean to be a CYP2D6 poor metabolizer?
A poor metabolizer has two non-functional copies of the CYP2D6 gene, meaning they cannot effectively process drugs that rely on this enzyme. This can lead to higher drug levels in the blood or a failure to activate prodrugs like codeine.
Is rs72549306 the same as the *6 allele?
Yes, the rs72549306 variant is the specific genetic change that defines the CYP2D6*6 allele. It is a single nucleotide deletion that causes a frameshift, rendering the enzyme non-functional.
Should I get tested for this variant before taking medication?
Routine testing for this specific variant is not standard for everyone. You should discuss the necessity of pharmacogenetic testing with your healthcare provider if you have experienced unusual side effects or lack of efficacy with medications metabolized by CYP2D6.
Can I change my CYP2D6 genotype?
No, your genotype is inherited from your parents and remains the same throughout your life. While you cannot change your genes, your doctor can adjust your medication or dosage based on your genetic profile.
Sources & further reading
Educational information only, last refreshed 9/19/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs72549306?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in CYP2D6
This variant is a key marker for the CYP2D6*10 allele, which results in reduced enzymatic activity and altered metabolism of various psychiatric and analgesic medications.
This variant defines the CYP2D6*4 non-functional allele, which causes impaired metabolism of numerous clinically prescribed medications including antidepressants, tamoxifen, and codeine.
Defines the CYP2D6*17 allele (p.Thr107Ile), which exhibits reduced enzyme activity towards substrates like codeine and certain antidepressants.
Defines the CYP2D6*29 variant (p.Val338Met) conferring decreased metabolic capacity, primarily observed in populations of African descent.
Promoter variant defining the CYP2D6*41 allele, associated with reduced enzyme expression and decreased metabolic capacity for various drugs.
Defines the non-functional CYP2D6*41 splice defect associated with intermediate metabolizer phenotype affecting codeine, tamoxifen, and SSRI metabolism.