NUDT15 rs116855232: What Your Genotype Means
The rs116855232 variant in the NUDT15 gene is a significant genetic marker associated with how the body processes thiopurine medications. Individuals carrying this variant may be at a higher risk for severe bone marrow toxicity when treated with these drugs.
What each genotype means
Normal enzyme activity
This genotype is associated with normal NUDT15 enzyme function, which is responsible for breaking down thiopurine medications. Individuals with this genotype typically metabolize these drugs at a standard rate. Please discuss your medication dosing and any potential side effects with your clinician or pharmacist.
This is the most common genotype in most global populations, though it is less frequent in East Asian populations where the T allele is more prevalent.
Reduced enzyme activity
This genotype indicates a reduced ability to metabolize thiopurine drugs, which may increase the risk of side effects like bone marrow toxicity or leukopenia. This variant is often referred to in clinical literature as part of the NUDT15 *2 or *3 star allele definitions. Please consult your healthcare provider or pharmacist to discuss how this genotype may influence your medication dosing.
This genotype is found in a significant portion of East Asian populations and is less common in individuals of European or African ancestry.
Significantly reduced enzyme activity
This genotype is associated with a high risk of severe, life-threatening bone marrow toxicity when taking standard doses of thiopurine medications due to significantly impaired enzyme function. Research consistently links this genotype to thiopurine intolerance and the need for substantial dose reductions or alternative therapies. It is essential to discuss this result with your clinician or pharmacist before starting or continuing any thiopurine treatment.
This genotype is rare globally but is observed more frequently in East Asian populations compared to other ancestral groups.
Understanding the rs116855232 Variant
The rs116855232 variant is a single nucleotide polymorphism (SNP) located within the NUDT15 gene on chromosome 13. In scientific literature, this specific change is often referred to as the R139C mutation, where a cytosine (C) is replaced by a thymine (T) at a specific position in the DNA sequence. This change results in an amino acid substitution (arginine to cysteine) in the NUDT15 protein. Because this variant alters the structure of the resulting enzyme, it is a critical focus in the field of pharmacogenomics—the study of how genes affect an individual's response to drugs. Identifying this variant is essential for clinicians, as it serves as a predictor for how a patient might tolerate specific classes of medication, particularly those used in chemotherapy and autoimmune treatments.
The Role of the NUDT15 Gene
The NUDT15 gene provides instructions for making an enzyme called nudix hydrolase 15. This enzyme plays a vital role in the metabolism of thiopurine drugs, such as mercaptopurine, azathioprine, and thioguanine. These medications are commonly used to treat conditions like acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). Under normal conditions, the NUDT15 enzyme helps break down thiopurine metabolites, preventing them from accumulating to toxic levels in the body. When the NUDT15 gene carries the rs116855232 variant, the resulting enzyme is often unstable or inactive. This leads to a reduced ability to clear the drug from the system, causing the active metabolites to build up. This accumulation can lead to excessive suppression of the bone marrow, which is responsible for producing blood cells, potentially resulting in life-threatening side effects.
Research and Clinical Evidence
The evidence linking rs116855232 to thiopurine-induced toxicity is considered strong. Numerous studies have demonstrated that individuals carrying the T allele are significantly more likely to experience early, severe leukopenia—a condition characterized by a low white blood cell count—when taking standard doses of thiopurines. Research has shown that the risk is particularly pronounced in patients who are homozygous for the variant (carrying two copies of the T allele). Because of these findings, clinical guidelines have been developed to help healthcare providers adjust dosages based on a patient's NUDT15 genotype. By identifying this variant before starting treatment, clinicians can often reduce the risk of severe adverse reactions, making this a successful example of personalized medicine in clinical practice.
Population Frequency
The frequency of the rs116855232 variant varies significantly across different ancestral groups. It is most commonly observed in East Asian populations, where the minor allele frequency can reach up to 10%. The variant is also found in individuals of South Asian and Hispanic descent. Conversely, the variant is considered rare in populations of European and African ancestry. Because of this uneven distribution, the clinical relevance of testing for this specific SNP is often prioritized in regions or populations where the variant is more prevalent. Understanding these population-specific differences is a key component of global health research, as it ensures that genetic screening programs are appropriately targeted to the groups that stand to benefit the most from personalized dosing strategies.
What This Information Means for You
If you are aware of your status for the rs116855232 variant, it is important to understand that this information is primarily intended for clinical decision-making regarding specific medications. This variant does not cause a disease on its own; rather, it influences how your body interacts with thiopurine drugs. If you have been prescribed or are considering treatment with medications like azathioprine or mercaptopurine, you should discuss your genetic status with your physician or pharmacist. They are the only ones qualified to interpret these results in the context of your overall health and determine if a dosage adjustment or an alternative treatment plan is necessary. Never make changes to your prescribed medication regimen based on genetic information without consulting a qualified healthcare professional.
How common is this variant?
The rs116855232 variant is found in up to 10% of East Asian populations, while it is considered rare in European and African populations.
Frequently asked questions
What is NUDT15-related thiopurine toxicity?
It is a condition where individuals with specific NUDT15 genetic variants cannot properly break down thiopurine drugs. This leads to a buildup of the drug in the body, which can cause severe bone marrow suppression and low blood cell counts.
Should I get tested for NUDT15?
Genetic testing for NUDT15 is typically recommended by clinicians before starting treatment with thiopurine medications. You should discuss the necessity of this test with your doctor if you are prescribed these drugs.
Does having the T allele mean I cannot take thiopurines?
Not necessarily. Having the T allele often means that your doctor may need to start you on a lower dose of the medication to ensure it is safe for you. Always follow the specific dosing instructions provided by your healthcare provider.
Is rs116855232 the same as NUDT15*3?
Yes, the rs116855232 variant is commonly referred to as the NUDT15*3 allele in pharmacogenetic literature. Both terms refer to the same genetic change that affects enzyme function.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is often confused with the primary NUDT15*3 (p.Arg139Cys) variant, which is rs116855232. rs116822326 is a distinct NUDT15 variant.
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.