NUDT15 rs116822326: What Your Genotype Means
The rs116822326 variant is a specific genetic change located within the NUDT15 gene. It is distinct from other well-known NUDT15 variants and is primarily studied for its potential role in how the body processes certain medications.
What each genotype means
Normal NUDT15 enzyme function
Research indicates that this genotype is associated with normal NUDT15 enzymatic activity in breaking down thiopurine metabolites. Individuals carrying this common profile generally tolerate standard thiopurine dosing protocols without elevated genetic risk from this specific locus. Always discuss personal medication response and dosing considerations with your physician or pharmacist.
Carried by the vast majority of individuals of European and African ancestry (>98%), and by roughly 80-85% of individuals of East Asian or Hispanic ancestry.
Intermediate NUDT15 metabolizer
This genotype carries one no-function *3 allele, which is associated with significantly reduced NUDT15 enzyme activity. Clinical studies correlate this profile with an increased susceptibility to early thiopurine-induced bone marrow suppression and leukopenia. Anyone prescribed thiopurine medications such as azathioprine or mercaptopurine should discuss personalized dosing and monitoring with their clinician or pharmacist.
Carried by approximately 15-20% of individuals of East Asian and Hispanic descent, but present in fewer than 1% of individuals of European ancestry.
Poor NUDT15 metabolizer
Carrying two copies of the variant allele (*3/*3) results in a severe loss of functional NUDT15 enzyme activity. Research strongly links this genotype to an extreme risk of life-threatening myelosuppression and severe leukopenia if standard thiopurine doses are administered. It is essential to discuss thiopurine dosing adjustments or alternative therapies directly with your clinician or pharmacist.
Observed in roughly 1-2% of East Asian individuals and rare individuals of Amerindian or Hispanic descent, while remaining extremely rare (<0.01%) in European populations.
Understanding the Variant
The rs116822326 variant is a single nucleotide polymorphism (SNP) found in the NUDT15 gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. It is important to distinguish this specific variant from others in the same gene, such as the widely studied p.Arg139Cys (rs116855232), which is often referred to as NUDT15*3. Because rs116822326 is a separate genetic marker, its clinical implications may differ from the more common variants that have been extensively characterized in pharmacogenomic guidelines. Researchers track these specific locations to understand how individual genetic differences contribute to biological diversity and, in some cases, variations in how people respond to therapeutic drugs.
The Role of the NUDT15 Gene
The NUDT15 gene encodes an enzyme called nudix hydrolase 15. This enzyme plays a critical role in cellular metabolism by acting as a diphosphatase, which helps regulate the levels of certain nucleotide metabolites. By breaking down these molecules, NUDT15 prevents the accumulation of toxic byproducts that could otherwise interfere with DNA synthesis and repair. In the context of pharmacogenomics, NUDT15 is best known for its role in metabolizing thiopurine drugs, which are commonly used to treat conditions like inflammatory bowel disease and certain types of leukemia. When NUDT15 activity is reduced due to genetic variation, the body may struggle to clear these drugs effectively, potentially leading to higher concentrations of active metabolites and an increased risk of side effects, such as myelotoxicity or leukopenia.
Research and Evidence Strength
The evidence linking rs116822326 to specific clinical outcomes is currently considered limited. While the NUDT15 gene as a whole is a well-established focus of pharmacogenomic research, not every variant within the gene carries the same level of clinical evidence. Many studies have focused on the functional impact of loss-of-function variants that significantly reduce enzyme activity. For rs116822326, further research is required to determine its precise impact on enzyme function and its correlation with drug-related side effects. Because the evidence is not as robust as it is for other NUDT15 variants, clinicians and researchers exercise caution when interpreting its significance. It is essential to rely on peer-reviewed literature and established clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC), when evaluating the relevance of specific genetic findings.
Population Frequency
The frequency of the rs116822326 variant varies significantly across different ancestral groups. Current data indicates that the minor allele frequency is approximately 7-10% in populations of East Asian and Hispanic ancestry. In contrast, the variant is much less common in populations of European ancestry, where the frequency is typically reported as less than 0.5%. These differences highlight the importance of considering ancestry in genetic research, as a variant that is relatively common in one population may be rare in another. Understanding these frequency distributions helps researchers design more inclusive studies and ensures that genetic insights are applicable to diverse groups of people.
What This Information Means for You
If you have received information about your rs116822326 genotype, it is important to understand that this is just one piece of a much larger biological puzzle. Genetic variants do not act in isolation, and many factors—including other genes, environmental influences, and overall health—contribute to how your body functions or responds to medication. This information should never be used to make independent medical decisions, such as starting, stopping, or changing the dosage of a prescribed medication. If you are concerned about how your genetics might influence your treatment, the best course of action is to discuss your results with your healthcare provider or a clinical pharmacist. They can interpret these findings within the context of your complete medical history and provide guidance tailored to your specific needs.
How common is this variant?
The minor allele frequency for rs116822326 is approximately 7-10% in East Asian and Hispanic populations, while it is less than 0.5% in European populations.
Frequently asked questions
Is rs116822326 the same as the common NUDT15*3 variant?
No, rs116822326 is a distinct genetic variant. It is often confused with the well-known p.Arg139Cys variant (rs116855232), but they are separate markers located at different positions in the gene.
Does this variant mean I will have a bad reaction to medication?
Not necessarily. While some NUDT15 variants are linked to drug sensitivity, the evidence for rs116822326 is limited. You should always consult your doctor before making any changes to your medication.
Where can I find more information about NUDT15 testing?
You can look for information on the Clinical Pharmacogenetics Implementation Consortium (CPIC) website or the PharmGKB database. These resources provide evidence-based guidelines for clinicians regarding gene-drug interactions.
Should I get tested for this specific variant?
Genetic testing should be discussed with a healthcare provider who can determine if it is clinically relevant for your specific health situation. Routine testing for every known variant is not always recommended or necessary.
Sources & further reading
Educational information only, last refreshed 10/28/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Missense variant (p.Val18Ile) defining the NUDT15*2 haplotype, associated with reduced thiopurine tolerance.
Splice/intronic regulatory modifier in NUDT15 associated with reduced enzyme level and enhanced susceptibility to thiopurine-induced severe leukopenia.
The NUDT15 p.Arg139Cys variant (defining the *3 allele) is a major determinant of thiopurine-induced myelosuppression.
NUDT15 c.55_56insGAGTCG (p.Val18_Gly19insGlyVal) defining the NUDT15*6 allele, associated with reduced enzyme activity and increased risk of thiopurine-induced leukopenia.
This variant is a defining marker for NUDT15 star alleles (*2, *6, *9) which are critical for predicting thiopurine-induced toxicity.
This variant (NUDT15 *3) is the primary predictor of severe, life-threatening bone marrow toxicity when taking thiopurine drugs.