CYP2D6 rs28371725: Understanding the *41 Reduced Function Allele
The rs28371725 variant is a genetic marker located within the CYP2D6 gene, commonly referred to as the *41 allele. It is associated with reduced enzyme activity, which can influence how an individual metabolizes various medications, including certain antidepressants and codeine.
What each genotype means
Normal enzyme activity
This genotype represents the reference state for this variant, which is typically associated with normal CYP2D6 enzyme function. Because CYP2D6 activity is determined by the entire gene sequence, you should discuss any medication-related concerns with your clinician or pharmacist to ensure a complete assessment of your metabolic profile.
This is the most common genotype observed in most global populations.
Reduced enzyme activity carrier
You carry one copy of the CYP2D6*41 allele, which is associated with reduced enzyme activity. This may influence how your body processes certain medications, such as specific antidepressants or codeine, though the overall impact depends on the function of your other CYP2D6 allele. Please consult your healthcare provider or pharmacist to discuss how this might affect your response to specific treatments.
Carried by a significant portion of individuals of European ancestry, often estimated at around 20% for the *41 allele presence.
Reduced enzyme activity
You carry two copies of the CYP2D6*41 allele, which is classified as a reduced-function variant. Research indicates this can lead to decreased metabolism of various drugs, potentially requiring dosage adjustments for medications processed by this enzyme. Always discuss your medication dosing and potential alternatives with your clinician or pharmacist.
This homozygous genotype is less common than the heterozygous state but is observed in populations of European descent.
What is the rs28371725 Variant?
The rs28371725 variant is a specific single nucleotide polymorphism (SNP) found within the CYP2D6 gene on chromosome 22. In the context of pharmacogenomics, this variant is widely recognized as a defining marker for the CYP2D6*41 haplotype. The CYP2D6 gene is highly polymorphic, meaning it exists in many different forms across the human population. When researchers identify the presence of the rs28371725 variant, they are often looking at how this specific change in the DNA sequence alters the structure or expression of the resulting enzyme. Because this variant is linked to a decrease in the enzyme's ability to perform its chemical tasks, it is classified as a 'reduced function' allele. Understanding this variant is a key part of modern pharmacogenomics, which seeks to explain why individuals may respond differently to the same standard dose of a medication.
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—or breakdown—of approximately 25% of all clinically prescribed drugs. Its substrates include a wide range of therapeutic agents, such as antidepressants, antipsychotics, beta-blockers, and pain medications like codeine. Codeine, for example, is a prodrug, meaning it must be converted by the CYP2D6 enzyme into its active form, morphine, to provide pain relief. When the CYP2D6 gene carries variants that reduce or eliminate the enzyme's function, the body's ability to process these drugs is altered. This can lead to either lower-than-expected levels of active medication or, in some cases, the accumulation of drugs that are not being cleared from the system efficiently.
Research and Clinical Associations
Scientific research has consistently identified the *41 allele (marked by rs28371725) as a reduced function variant. Clinical studies have shown that individuals carrying this allele may exhibit 'intermediate' or 'normal' metabolizer status, depending on the other copy of the gene they possess. For instance, if an individual inherits one reduced-function *41 allele and one non-functional allele, they may be classified as an intermediate metabolizer. The evidence for this association is considered moderate to strong in the field of pharmacogenomics. However, the clinical impact can be complex; some studies suggest that the metabolic effect of *41 can be influenced by other genetic factors, such as gene copy number variations. Because of this complexity, researchers emphasize that genotype alone does not always perfectly predict how a person will respond to a drug, and clinical phenotyping is sometimes used to confirm metabolic status.
What You Can Do With This Information
If you have information about your CYP2D6 genotype, it is important to view it as a piece of a larger clinical puzzle rather than a definitive medical diagnosis. Genetic variants like rs28371725 provide insights into your potential metabolic profile, but they do not dictate your health outcomes. You should never use genetic test results to start, stop, or change the dosage of any medication on your own. Instead, share this information with your healthcare provider or a clinical pharmacist. They are trained to interpret these results in the context of your overall health, current medications, and medical history. A clinician can determine if a dosage adjustment or an alternative medication is appropriate for you based on your specific genetic profile and clinical needs.
How common is this variant?
The CYP2D6*41 allele is common in European populations, with a frequency of approximately 10% to 20%. It is also identified as a major reduced-function allele in Indian and Saudi Arabian populations.
Frequently asked questions
What does it mean to be a CYP2D6 intermediate metabolizer?
An intermediate metabolizer has a reduced ability to process certain drugs compared to a normal metabolizer. This may result in slower clearance of a medication from the body, which could potentially increase the risk of side effects or require dosage adjustments.
Does having the *41 allele mean I cannot take codeine?
Not necessarily, but it may affect how well your body converts codeine into morphine. You should discuss your specific genotype with your doctor, who can determine if codeine is the right choice for your pain management or if an alternative is safer.
Is the rs28371725 test the same as a full CYP2D6 genetic test?
No, rs28371725 is just one specific variant. A comprehensive CYP2D6 test often looks at many different variants and gene copy numbers to provide a more complete picture of your metabolic status.
Can my CYP2D6 status change over time?
Your genetic genotype is fixed at birth and does not change. However, other factors like age, liver health, and other medications you are taking can influence how your CYP2D6 enzyme functions in real-time.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.