CYP2D6 rs35744814: Understanding Genetic Influence on Drug Metabolism
The rs35744814 variant is a specific genetic change located within the CYP2D6 gene. It is classified as a null variant, meaning it is associated with a total lack of functional CYP2D6 enzyme activity in individuals who carry it.
What each genotype means
Normal enzyme activity
This genotype represents the functional, wild-type version of the CYP2D6 enzyme. Individuals with this profile typically possess normal metabolic capacity for drugs processed by this pathway. Please discuss any medication dosing or potential side effects with your clinician or pharmacist.
This is the most common genotype in most global populations, though frequencies vary significantly by ancestry.
Reduced enzyme activity
This genotype indicates you carry one copy of the non-functional rs35744814 variant, often referred to as part of the CYP2D6*3 allele. You may have reduced ability to process certain medications compared to individuals with two functional copies. Please consult your healthcare provider or pharmacist regarding how this may influence your response to specific prescriptions.
This heterozygous genotype is found in a minority of individuals, with prevalence varying by geographic and ethnic background.
Total lack of enzyme activity
This genotype indicates you carry two copies of the non-functional rs35744814 variant, which is associated with a 'poor metabolizer' phenotype. Because this variant causes a total lack of CYP2D6 enzyme activity, your body may process certain medications much more slowly than expected. It is essential to discuss this result with your clinician or pharmacist before starting or adjusting any medications metabolized by this enzyme.
This homozygous genotype is relatively rare, occurring in approximately 2% of individuals of European ancestry and at varying, often lower, frequencies in other populations.
What is the rs35744814 Variant?
The rs35744814 variant is a single nucleotide polymorphism (SNP) found within the CYP2D6 gene, which is located on chromosome 22. In the context of pharmacogenomics, this variant is categorized as a 'null' allele. This means that the genetic change prevents the production of a functional CYP2D6 enzyme. Because the CYP2D6 gene is highly polymorphic—meaning it has many different variations—researchers use 'star allele' nomenclature to group these variants. The rs35744814 variant is one of the specific markers used to identify alleles that result in a complete loss of enzyme function. When an individual inherits this variant, their ability to metabolize certain substances is significantly altered compared to individuals who carry fully functional versions of the gene.
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 breaking down, or metabolizing, approximately 25% of all commonly prescribed medications. These include various antidepressants, opioids, and tamoxifen. Because this enzyme is so critical for drug clearance, genetic variations in the CYP2D6 gene can lead to significant differences in how people respond to medications. Some individuals are 'normal metabolizers,' while others may be 'poor metabolizers' if they carry variants like rs35744814 that reduce or eliminate enzyme activity. Understanding these genetic differences is a key component of pharmacogenomics, a field that aims to tailor medical treatments to an individual's unique genetic makeup to improve efficacy and reduce the risk of adverse side effects.
Research and Clinical Associations
Scientific research has established a strong link between null CYP2D6 variants and the 'poor metabolizer' phenotype. When a person has two non-functional copies of the gene, they may experience higher blood concentrations of drugs that are normally cleared by the CYP2D6 enzyme, potentially increasing the risk of side effects. Conversely, for 'prodrugs'—medications that must be activated by the enzyme to work—a lack of CYP2D6 activity may result in the drug being ineffective. The evidence for the impact of null variants on drug metabolism is well-documented in clinical guidelines, such as those provided by the Clinical Pharmacogenetics Implementation Consortium (CPIC). However, it is important to note that clinical outcomes are complex and can be influenced by other factors, including drug-drug interactions, age, and liver health. Always consult with your clinician or pharmacist regarding how your specific genetic profile might influence your response to a prescribed medication.
Population Frequency and Distribution
Genetic variants in the CYP2D6 gene are not distributed equally across the globe; their frequencies vary significantly among different ancestral populations. For the rs35744814 variant specifically, current data indicates a frequency of approximately 2% in European populations. Because CYP2D6 is highly polymorphic, other null variants, such as CYP2D6*4 and CYP2D6*5, are also prevalent in various groups and contribute to the overall percentage of poor metabolizers in those populations. For example, while European populations may have a specific distribution of null alleles, other populations, such as those of East Asian or African descent, may show different frequencies of both null and decreased-function alleles. These inter-ethnic differences highlight the importance of considering ancestry when interpreting pharmacogenetic data, as the prevalence of specific variants can change the likelihood of an individual being a poor metabolizer.
What You Can Do With This Information
Knowing your status for the rs35744814 variant can be a valuable piece of information for your healthcare team. If you have undergone genetic testing and identified this variant, it is essential to share these results with your doctor or pharmacist. They can use this information to make informed decisions about medication selection and dosing, particularly for drugs known to be metabolized by CYP2D6. It is important to remember that this information is not a diagnosis and should never be used to change or stop a medication on your own. Pharmacogenomics is a tool to assist clinicians in optimizing therapy, not a replacement for professional medical judgment. Always discuss any concerns about your genetic test results or your current treatment plan with a qualified healthcare provider who can interpret the findings in the context of your overall health.
How common is this variant?
The rs35744814 variant is observed at a frequency of approximately 2% in European populations, though the prevalence of various CYP2D6 null alleles differs significantly across global ancestries.
Frequently asked questions
What does it mean to be a CYP2D6 poor metabolizer?
A poor metabolizer has little to no functional CYP2D6 enzyme activity. This means the body processes certain medications much slower than average, which can lead to higher drug levels in the blood and an increased risk of side effects.
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, knowing your genotype helps your doctor choose the right medication and dose for you.
Does having this variant mean I will have bad reactions to all drugs?
No, this variant only affects drugs that are specifically processed by the CYP2D6 enzyme. Many other medications are metabolized by different enzymes and would not be affected by your CYP2D6 status.
Should I get tested for CYP2D6 variants?
Genetic testing for CYP2D6 is typically recommended by healthcare providers when you are prescribed a medication that is known to be affected by this gene. You should discuss the necessity of such testing with your doctor based on your specific medical needs.
Sources & further reading
Educational information only, last refreshed 10/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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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.