CYP2D6 rs1135638: Understanding Your Genetic Drug Metabolism
The rs1135638 variant is a specific genetic change within the CYP2D6 gene that defines the *10 allele. This variant is associated with decreased enzymatic activity, which can influence how an individual's body processes various medications.
What each genotype means
Normal enzyme activity
This genotype represents the wild-type or fully functional version of the CYP2D6 enzyme. Individuals with this profile typically exhibit normal metabolic activity for drugs processed by this pathway. Please consult with your clinician or pharmacist regarding how your specific genotype may influence your response to medications.
This is the most common genotype in European and African populations, but it is less frequent in East Asian populations where the T allele is highly prevalent.
Intermediate enzyme activity
This genotype includes one copy of the variant associated with the CYP2D6*10 allele, which is known to confer decreased enzymatic activity. You may metabolize certain medications more slowly than individuals with the CC genotype. Please discuss your medication dosing and potential side effects with your healthcare provider or pharmacist.
This genotype is very common in East Asian populations, reflecting the high prevalence of the CYP2D6*10 allele in those groups.
Reduced enzyme activity
This genotype consists of two copies of the variant associated with the CYP2D6*10 allele, which is linked to reduced CYP2D6 enzyme function. This may lead to slower processing of specific drugs, potentially increasing the risk of side effects or requiring dosage adjustments. Always consult your clinician or pharmacist before making changes to your medication regimen.
This genotype is frequently observed in East Asian populations, where the CYP2D6*10 allele is common, but it is relatively rare in European and African ancestries.
What is the rs1135638 Variant?
The rs1135638 variant is a single-nucleotide polymorphism (SNP) located within the CYP2D6 gene. In scientific literature, this specific change is often referred to as the defining marker for the CYP2D6*10 allele. At the molecular level, this variant involves a substitution where a cytosine (C) is replaced by a thymine (T) at a specific position in the DNA sequence. This change results in a non-synonymous mutation, meaning it alters the amino acid sequence of the resulting protein—specifically changing serine to leucine at position 289. Because the CYP2D6 enzyme is responsible for breaking down many different substances, changes to its structure can lead to functional differences in how the enzyme operates. This SNP is a primary focus in pharmacogenomics because it serves as a reliable indicator for identifying individuals who may have reduced capacity to metabolize certain drugs.
The Role of the CYP2D6 Gene
The CYP2D6 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily found in the liver and are essential for the metabolism of a wide variety of compounds, including approximately 20% to 25% of all clinically used medications. CYP2D6 is responsible for processing drugs such as antidepressants, antipsychotics, opioid analgesics, and certain antihypertensives. Because the gene is highly polymorphic—meaning it has many different variations—the activity of the resulting enzyme can range from completely absent to significantly increased. When a person carries variants like rs1135638, the enzyme may function less efficiently than the standard version. This reduced function can lead to slower clearance of drugs from the bloodstream, potentially increasing the concentration of the medication in the body and affecting both the efficacy of the treatment and the risk of experiencing adverse side effects.
Research and Clinical Evidence
Research into rs1135638 is grounded in the field of pharmacogenomics, which studies how genetic variations influence drug response. The evidence linking this variant to decreased enzymatic activity is well-documented in clinical guidelines, such as those provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC). While the association between the *10 allele and reduced metabolism is strong, the clinical impact for any individual depends on the specific drug being prescribed and the person's overall genetic profile. It is important to note that pharmacogenomic evidence is often complex; while some drugs may require dosage adjustments for individuals with this variant, others may not be affected at all. Because of this, the evidence strength for clinical decision-making is considered specific to the medication in question. Always consult with your physician or a clinical pharmacist to interpret how your specific genetic results might relate to your current or future medication regimen.
What You Can Do With This Information
Understanding your genetic variants can be a powerful tool for personal health management, but it is not a substitute for professional medical advice. If you have received information about your rs1135638 status, the most important step is to share this data with your healthcare provider. They can determine if your genotype is relevant to the medications you are currently taking or may need in the future. You cannot use this information to diagnose yourself or to make independent decisions about changing your medication dosages. Genetic testing provides only one piece of the puzzle; clinicians also consider factors like your age, weight, liver function, and other medications you may be taking. By discussing your genetic profile with a qualified professional, you ensure that any adjustments to your treatment plan are made safely and based on the most current clinical guidelines.
How common is this variant?
The rs1135638 variant is highly prevalent in East Asian populations, with frequencies often ranging between 40% and 50%. In contrast, it is relatively uncommon in European and African populations, typically appearing at frequencies of 2% to 5%.
Frequently asked questions
Does having the rs1135638 variant mean I will have bad side effects from medication?
Not necessarily. While this variant is associated with decreased enzyme activity, whether you experience side effects depends on the specific drug, your dosage, and other individual health factors. Always discuss your genetic results with your doctor.
Is rs1135638 the same as CYP2D6*10?
Yes, rs1135638 is the defining single-nucleotide polymorphism for the CYP2D6*10 allele. In clinical reports, you may see it referred to by either the rsID or the star allele notation.
Should I change my medication if I have this variant?
No. You should never change your medication or dosage based on genetic test results without consulting your healthcare provider. Only a clinician can determine if a change is necessary based on your full medical history.
Why is this variant more common in some populations than others?
Genetic variations often become more or less common in specific populations due to historical migration patterns, natural selection, and genetic drift. The high frequency of this variant in East Asian populations is a well-documented observation in human genetics.
Sources & further reading
Educational information only, last refreshed 9/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1135638?
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.