CYP2C9 rs61747863: What Your Genotype Means
The genetic variant rs61747863 is a single-nucleotide polymorphism located within the CYP2C9 gene, defining the pharmacogenomic missense substitution known as CYP2C9*11 (p.Arg335Trp). This variant results in an enzyme with markedly decreased or absent catalytic activity, altering how the body processes several common prescription medications. Individuals carrying the variant allele frequently demonstrate impaired systemic clearance of narrow therapeutic index drugs, most notably the oral anticoagulant warfarin, the anticonvulsant phenytoin, and certain nonsteroidal anti-inflammatory drugs (NSAIDs).
What each genotype means
Normal CYP2C9 enzyme activity
You carry two reference copies at this genomic position and do not carry the CYP2C9*11 allele. Individuals with this genotype typically demonstrate normal baseline metabolism of CYP2C9-cleared medications like warfarin, phenytoin, and certain NSAIDs, assuming no other altering variants are present. Always consult a physician or pharmacist to discuss your medication plan and any recommended dosing.
Carried by over 95% of individuals of African ancestry and virtually 99.5% or more of individuals of European, Asian, and other global populations.
Reduced CYP2C9 enzyme activity
You carry one copy of the CYP2C9*11 variant allele, which is associated with decreased catalytic activity of the CYP2C9 enzyme. Clinical research indicates that carriers typically clear medications such as warfarin, phenytoin, and specific NSAIDs more slowly, potentially increasing drug exposure. Because research on this specific variant is limited and largely characterized in African-ancestry populations, discuss dosing requirements with your clinician or pharmacist.
Found in approximately 2% to 5% of individuals of African ancestry; it is exceedingly rare (under 0.5%) in European and Asian populations.
Significantly reduced enzyme activity
You carry two copies of the CYP2C9*11 allele, which is predicted to cause a marked reduction in CYP2C9 drug clearance. Homozygous individuals are expected to metabolize substrates like warfarin and phenytoin much more slowly, raising the likelihood of adverse effects at standard doses. Do not adjust any medications independently; discuss specific dosing and monitoring with your healthcare provider or pharmacist.
Extremely rare across all populations, occurring in fewer than 1 in 1,000 individuals of African ancestry and almost never observed in other groups.
What Is rs61747863 and Where Does It Sit?
The variant rs61747863 represents a single-nucleotide transition (c.1003C>T) in the CYP2C9 gene, positioned on the long arm of chromosome 10 (10q24). In the open reading frame, this substitution changes codon 335 from cytosine to thymine, replacing a positively charged arginine residue with an aromatic tryptophan (p.Arg335Trp). This altered position falls within a highly conserved structural domain of the cytochrome P450 enzyme. Biochemical research indicates that the introduction of tryptophan at position 335 disrupts the enzyme's thermal stability and normal folding conformation. Consequently, the mutated protein exhibits a substantially shortened half-life and impaired catalytic efficiency when interacting with target chemical substrates. In pharmacogenetic nomenclature maintained by the Pharmacogene Variation (PharmVar) Consortium and the Clinical Pharmacogenetics Implementation Consortium (CPIC), this specific nucleotide change forms the core defining marker of the CYP2C9*11 haplotype.
The Role of the CYP2C9 Enzyme in Drug Metabolism
The CYP2C9 gene encodes Cytochrome P450 2C9, an essential phase I hepatic monooxygenase responsible for metabolizing approximately 15% to 20% of all clinically prescribed drugs. Located within the smooth endoplasmic reticulum of liver cells, CYP2C9 oxidizes xenobiotics to make them more water-soluble for excretion. CYP2C9 plays a critical role in clearing medications that possess narrow therapeutic indices—meaning that a minor change in drug blood concentration can mean the difference between therapeutic efficacy and serious toxicity. Its principal substrates include the S-enantiomer of warfarin (responsible for most of warfarin's anticoagulant potency), the anti-seizure medication phenytoin, and various NSAIDs such as celecoxib, ibuprofen, and meloxicam. When functional CYP2C9 enzyme levels drop, active drug molecules linger in circulation longer than expected, increasing circulating exposure and drug sensitivity.
What Research Associates rs61747863 With: Evidence and Impact
Current peer-reviewed studies associate the CYP2C9*11 allele with a substantial decrease in drug clearance. In vivo pharmacokinetic investigations have shown that individuals carrying one copy of the variant (a CYP2C9*1/*11 diplotype) experience a greater than 50% reduction in the oral clearance of S-warfarin and reduced phenytoin clearance compared to individuals with normal enzyme function (*1/*1). This functional impairment closely mirrors the enzymatic reduction observed with CYP2C9*3, one of the most widely recognized non-functional alleles. Because of this decreased metabolic capacity, carriers typically require significantly lower maintenance doses of warfarin to achieve target anticoagulation levels. If prescribed standard starting doses, carriers face an elevated risk of drug accumulation, over-anticoagulation, and dangerous bleeding episodes. Phenytoin administration in variant carriers has similarly been linked to toxic plasma concentrations, manifesting as neurological side effects such as ataxia and nystagmus. Furthermore, impaired NSAID clearance can prolong systemic drug exposure, raising the likelihood of adverse gastrointestinal or cardiovascular events. While the biological impact on enzyme kinetics is well-characterized, the overall clinical evidence strength remains categorized as "Limited" compared to older European-centric alleles (*2 and *3), primarily because fewer large-scale clinical trials have systematically tracked CYP2C9*11 cohorts.
Population Frequency and Ancestral Diversity
The allele frequency of rs61747863 demonstrates significant variation across global ancestral groups. It is predominantly identified in individuals of African ancestry, where the minor allele frequency (MAF) typically ranges between 0.01 and 0.03 (1% to 3%), reaching up to 5% in specific West African populations. In contrast, the variant is extremely rare in individuals of European, East Asian, and Native American descent, often occurring at frequencies below 0.002 or missing altogether from standard screening panels. Historically, major clinical trials on warfarin dosing algorithms only genotyped European-common variants (CYP2C9*2 and *3), which inadvertently led to systematic over-dosing and poor predictive accuracy in African American patients. Incorporating CYP2C9*11 alongside alleles like *5, *6, and *8 has become a focal point in efforts to resolve ancestral health disparities in pharmacogenomics.
What You Can and Cannot Do With This Information
Understanding your rs61747863 genotype can provide valuable insight into how your liver handles certain medications, but genetic information is only one part of clinical care. A non-functional genotype does not mean you can never take warfarin, phenytoin, or NSAIDs; rather, it highlights that standard doses may cause drug accumulation. This information cannot diagnose a disease or predict whether you will suffer an adverse reaction with absolute certainty. Renal function, age, body weight, liver health, dietary vitamin K, and concomitant medications that inhibit or induce CYP enzymes also shape drug clearance. Never alter, reduce, or stop any prescribed medication based on a commercial DNA test. If you carry the variant allele and are prescribed or considering therapy with warfarin, phenytoin, or related drugs, consult your physician or clinical pharmacist to review genotype-guided dosing guidelines.
How common is this variant?
According to global genomic datasets, rs61747863 is an ancestry-specific variant with a minor allele frequency of approximately 0.01 to 0.03 in populations of African ancestry. In contrast, it is exceptionally rare (allele frequency < 0.002) or absent among individuals of European, East Asian, and other non-African ancestries.
Frequently asked questions
What does the CYP2C9 rs61747863 variant do?
The rs61747863 variant causes a missense mutation (p.Arg335Trp) in the CYP2C9 gene, defining the CYP2C9*11 allele. This change impairs the protein’s physical stability and catalytic function, significantly slowing the liver’s clearance of medications like warfarin, phenytoin, and certain NSAIDs.
Why is this variant more relevant in people of African ancestry?
While common variants like CYP2C9*2 and *3 predominate in European populations, CYP2C9*11 is primarily observed in individuals of African ancestry (occurring at a 1% to 3% frequency). Including this allele in genetic testing panels helps prevent the inaccurate over-dosing of medications that historically occurred when algorithms relied exclusively on European genetic data.
Does having this variant mean I cannot take warfarin or NSAIDs?
No. Carrying the variant does not strictly prohibit the use of these medications. However, because your liver breaks them down more slowly, clinical guidelines (such as those from CPIC) recommend lower starting doses, extended dosing intervals, or alternative therapies to avoid adverse bleeding or toxicity.
Can I change my medication dosage if my test says I carry this variant?
No, you should never adjust prescription doses on your own. Pharmacogenomic test results should be reviewed with your doctor or pharmacist, who will incorporate other factors—such as age, organ function, and concurrent medications—to determine safe dosing.
How strong is the clinical evidence for rs61747863?
The biological effect of CYP2C9*11 on enzyme function is well established in laboratory and pharmacokinetic studies, showing over a 50% reduction in activity. However, broad clinical trial data are more limited compared to older European markers because historical trials frequently omitted African-prevalent alleles from their testing panels.
Sources & further reading
Educational information only, last refreshed 9/14/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant in the CYP2C9 gene is associated with reduced enzyme activity, impacting the metabolism and required dosage of drugs like phenytoin and warfarin.
This rare variant results in a V to L or V to M amino acid substitution in the CYP2C9 enzyme, which is critical for drug metabolism.
Coding variant conferring the CYP2C9*4 allele with decreased enzymatic activity affecting clearance of drugs such as warfarin and phenytoin.
Missense mutation defining the CYP2C9*5 allele that dramatically lowers metabolic activity towards oral anticoagulants and anti-epileptic medications.
A rare variant in the CYP2C9 gene that may impact the metabolism of various clinical drugs.
Defining the CYP2C9*3 (p.Ile359Leu) allele, this variant markedly decreases enzymatic activity, requiring reduced dosages for warfarin and phenytoin to prevent toxicity.