CYP2C9 rs1799839: What Your Genotype Means
The genetic variant rs1799839, situated within the CYP2C9 gene on chromosome 10, defines the well-characterized CYP2C9*2 missense allele. This single-nucleotide polymorphism causes an amino acid substitution (Arg144Cys) that moderately reduces the enzymatic activity of cytochrome P450 2C9. As a result, carriers demonstrate altered baseline metabolism of endogenous compounds like fatty acids and steroids, as well as reduced clearance for certain medications.
What each genotype means
Normal enzyme activity
This genotype represents the most common form of the CYP2C9 enzyme, often referred to as the *1/*1 wild-type. Individuals with this profile typically exhibit standard metabolic activity for drugs processed by this enzyme. Please discuss any medication dosing or potential drug interactions with your clinician or pharmacist.
This is the most common genotype globally, found in the vast majority of individuals across all ancestral populations.
Reduced enzyme activity
This genotype, often referred to as the *1/*2 allele combination, is associated with reduced catalytic activity of the CYP2C9 enzyme. This may influence how your body processes certain medications, such as S-warfarin, potentially requiring dosage adjustments. Please consult with your healthcare provider or pharmacist regarding how this may affect your specific treatment plan.
Carried by roughly 1 in 5 to 1 in 8 people of European ancestry; it is significantly less common in East Asian and African populations.
Significantly reduced enzyme activity
This genotype, often referred to as the *2/*2 allele combination, is associated with a more pronounced reduction in CYP2C9 enzyme activity compared to the wild-type. This can lead to slower metabolism of specific drugs, which may increase the risk of side effects or require lower doses. Always discuss your genetic profile and medication management with your clinician or pharmacist.
This genotype is rare, occurring in approximately 1% to 2% of European populations and is extremely uncommon or absent in many other ancestral groups.
Genetic Location and Molecular Biology of rs1799839
The single-nucleotide polymorphism rs1799839 represents a cytosine-to-thymine (C>T) transition located in exon 3 of the CYP2C9 gene on chromosome 10q23.33. This base substitution changes codon 144 from an arginine to a cysteine residue (Arg144Cys), designating the CYP2C9*2 star allele. Structurally, this substitution occurs in a region that interacts with cytochrome P450 oxidoreductase, an essential electron-donating partner for the enzyme. By impairing this molecular interaction, the *2 allele reduces intrinsic catalytic efficiency, resulting in a partially functioning enzyme compared to the reference CYP2C9*1 allele. In functional assays, the *2 variant typically displays a 30% to 50% decrease in turnover capacity depending on the specific substrate tested.
The Physiological Role of the CYP2C9 Enzyme
The CYP2C9 gene encodes a member of the cytochrome P450 superfamily of monooxygenases, which are predominantly expressed in the liver and small intestine. CYP2C9 is integral to endogenous physiology, participating in the epoxygenation and hydroxylation of polyunsaturated fatty acids, such as arachidonic acid, into biologically active epoxyeicosatrienoic acids (EETs). These metabolites play pivotal roles in blood pressure maintenance, vascular inflammation, and renal function. Additionally, CYP2C9 contributes to the endogenous breakdown of steroid hormones and fat-soluble vitamins. Beyond internal metabolism, CYP2C9 clears an estimated 15% to 20% of clinically prescribed medications, including nonsteroidal anti-inflammatory drugs, oral hypoglycemics, and oral anticoagulants such as warfarin.
Research Associations and Evidence Strength
The association between rs1799839 and decreased enzymatic metabolism is well-documented and robust in pharmacogenetic literature according to databases like [ClinPGx](https://www.clinpgx.org) and [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/1559). Multiple peer-reviewed studies show that carriers of the *2 allele exhibit reduced clearance of narrow therapeutic index therapeutics, requiring lower maintenance doses to achieve standard therapeutic outcomes. However, when evaluating its non-pharmacological influence as an isolated trait—specifically its downstream impact on systemic fatty acid levels, steroid metabolism, and baseline cardiovascular risk—the evidence strength remains limited. While laboratory models confirm altered baseline lipid hydroxylation, broad population-level health endpoints directly caused solely by rs1799839 remain subject to ongoing investigation.
Ancestry and Population Patterns
The prevalence of the rs1799839 variant differs substantially among global ancestral groups, as recorded in public catalogs like [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC9160216/) and dbSNP. The alternative T allele is most prevalent among populations of European ancestry, occurring at an allele frequency of approximately 12% (~0.12). In contrast, the variant is observed at markedly lower rates in other global populations, showing an allele frequency of approximately 3% (~0.03) in individuals of African ancestry and less than 2% (<0.02) in East Asian populations. These population-level frequency differences are an important consideration in clinical research and help explain varying baseline frequencies of intermediate metabolizer phenotypes across distinct demographic cohorts worldwide.
Interpreting Your Genetic Information Responsibly
Identifying your rs1799839 genotype provides educational insight into your baseline liver enzyme function, but it is not a diagnostic test. A genotype indicating decreased enzyme activity does not guarantee adverse effects, nor does it replace professional clinical monitoring. Environmental factors, dietary components, age, liver health, and concurrent medications also influence enzyme capacity. Most crucially, if you carry a variant associated with altered drug metabolism, you must never modify, begin, or discontinue any prescribed medication or adjust your dosing regimen on your own. Always discuss any genetic results and medication-related questions directly with a licensed physician or pharmacist.
How common is this variant?
The rs1799839 T allele is most frequent in individuals of European descent at approximately 12%, while remaining infrequent in African populations (~3%) and East Asian populations (<2%).
Frequently asked questions
What is the CYP2C9 rs1799839 genetic variant?
rs1799839 is a single-nucleotide variant in the CYP2C9 gene, commonly referred to in medical genetics as the CYP2C9*2 allele. It alters one amino acid in the enzyme, changing an arginine to a cysteine at position 144, which reduces the enzyme's catalytic efficiency.
Does having the rs1799839 variant mean I am sick?
No, carrying the rs1799839 variant is not a disease or diagnosis. It simply indicates that your body produces a version of the CYP2C9 liver enzyme that processes certain fatty acids and medications more slowly than the standard form.
Can rs1799839 affect how I process medications?
Yes, research indicates that the CYP2C9*2 allele is associated with slower clearance of certain pharmaceuticals metabolized by CYP2C9, such as warfarin, phenytoin, and certain nonsteroidal anti-inflammatory drugs. Because dosage requirements may differ, any adjustments to prescription therapy should always be managed by your doctor or pharmacist.
Should I alter my prescriptions if I have the T allele?
No, you should never alter your medication dosage or stop taking a prescription based on a genetic test result. If you discover you have a reduced-function CYP2C9 variant, share these findings with your clinician, who can evaluate whether dosing adjustments or therapeutic monitoring are warranted.
Sources & further reading
Educational information only, last refreshed 9/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in CYP2C9
Rare variant in the CYP2C9 gene potentially impacting enzyme activity and drug metabolism; clinical significance requires further validation.
Coding variant conferring the CYP2C9*3 allele (often mislabeled as *4 in older literature) 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.
The CYP2C9*2 variant (p.Arg144Cys) results in reduced enzymatic activity, significantly impacting the metabolism and required dosing of substrates such as warfarin and irbesartan.
Defining the CYP2C9*3 (p.Ile359Leu) allele, this variant markedly decreases enzymatic activity, requiring reduced dosages for warfarin and phenytoin to prevent toxicity.