NUDT15 rs186364861: What Your Genotype Means
The rs186364861 variant is a rare genetic change located within the NUDT15 gene. Researchers investigate this variant to determine if it influences how individuals process thiopurine medications, which are often used to treat conditions like leukemia and inflammatory bowel disease.
What each genotype means
Normal enzyme activity
This genotype represents the typical sequence for the NUDT15 gene. Individuals with this profile are generally expected to have normal NUDT15 enzyme function, which is involved in the metabolism of thiopurine medications. Please discuss your medication dosing and any potential side effects with your clinician or pharmacist.
This is the most common genotype across all global populations.
Reduced enzyme activity
This genotype includes one variant allele (often referred to as NUDT15*5) which may lead to reduced NUDT15 enzyme activity. Reduced activity can influence how your body processes thiopurine drugs, potentially increasing the risk of side effects like leukopenia. Please consult your healthcare provider or pharmacist to discuss how this genetic finding may impact your specific treatment plan.
This genotype is rare and primarily observed in specific ancestral groups, including individuals of Asian and Hispanic descent.
Significantly reduced enzyme activity
This genotype involves two copies of the variant allele, which is associated with significantly decreased or absent NUDT15 enzyme activity. Research indicates that individuals with this profile may be at a much higher risk for severe thiopurine-induced toxicity, such as early-onset leukopenia. It is essential to discuss this result with your clinician or pharmacist before starting or continuing any thiopurine therapy.
This genotype is extremely rare across all studied populations.
Understanding the rs186364861 Variant
The rs186364861 variant is a specific change in the DNA sequence of the NUDT15 gene, which is located on chromosome 13. In the field of pharmacogenomics, scientists study such variants to understand how inherited differences in our genetic code can influence the body's response to drugs. While many variants in the NUDT15 gene have been extensively studied for their impact on drug metabolism, rs186364861 is classified as a rare variant. Because it is not as common as other well-known NUDT15 markers, it is the subject of ongoing research to clarify its functional impact. Genetic variants like this one are identified through high-throughput sequencing technologies that allow researchers to scan the genome for subtle differences that might explain why some patients experience different side effects or treatment outcomes than others when taking the same medication.
The Role of the NUDT15 Gene
The NUDT15 gene provides instructions for making an enzyme called nudix hydrolase 15. This enzyme plays a critical role in the body by breaking down certain metabolites of thiopurine drugs, such as mercaptopurine and azathioprine. These medications are frequently prescribed for pediatric acute lymphoblastic leukemia and various autoimmune conditions. When the NUDT15 enzyme functions normally, it helps regulate the levels of active thiopurine metabolites in the body. However, if the gene contains variants that reduce the enzyme's activity, these metabolites can accumulate to toxic levels. This accumulation is a known risk factor for myelosuppression, a condition where the bone marrow produces fewer blood cells, leading to leukopenia. Understanding how specific variants affect this enzyme is essential for developing safer, personalized dosing strategies for patients who require thiopurine therapy.
Research and Evidence Strength
The evidence linking rs186364861 to clinical outcomes is currently considered moderate or limited. While the broader NUDT15 gene is well-established as a major factor in thiopurine toxicity, not every individual variant within the gene has been definitively proven to cause clinical symptoms. Some studies have investigated this specific variant in the context of pediatric leukemia, but results have been mixed, with some analyses reporting that the association with adverse reactions is not statistically significant. Because this variant is rare, it is difficult for researchers to gather large enough datasets to reach a definitive conclusion about its impact. Consequently, while it is cataloged in pharmacogenomic databases, it is not currently used as a primary marker for clinical decision-making in the same way that more common, high-impact NUDT15 variants are. Further research is required to determine if this variant truly influences drug safety.
Population Frequency
The rs186364861 variant is classified as rare across global populations. Because of its low frequency, it is not commonly encountered in standard clinical screening panels, which typically focus on the most prevalent variants known to have a high impact on drug metabolism. The distribution of such rare variants can vary significantly between different ancestral groups, but current data does not suggest a high prevalence in any major population. Researchers often use large-scale genomic databases to track the frequency of these variants, but for rare markers like rs186364861, the data remains sparse. This rarity is a primary reason why the clinical significance of the variant remains uncertain, as there are few documented cases to study in a clinical setting.
What This Information Means for You
If you have received information about your status for the rs186364861 variant, it is important to understand that this is a research-level finding rather than a diagnostic result. Because the evidence for this specific variant is limited and sometimes conflicting, it should not be used to make changes to your medication regimen. Pharmacogenomic testing is a complex field, and clinical decisions regarding thiopurine dosing are based on a combination of genetic markers, blood count monitoring, and overall health status. You should never stop or adjust your medication based on a genetic report without consulting your healthcare provider. If you are concerned about potential side effects or the safety of your current treatment, speak with your doctor or a clinical pharmacist. They can provide guidance based on established clinical guidelines and your specific medical history.
How common is this variant?
The rs186364861 variant is considered rare across all major ancestral populations, with limited data available regarding its specific frequency in global cohorts.
Frequently asked questions
Is rs186364861 the same as other NUDT15 variants?
No, rs186364861 is a distinct genetic variant. While it is located in the same gene as well-known variants like those found in the *2 or *3 alleles, it is a different specific change in the DNA sequence.
Should I change my medication if I have this variant?
No. You should never change your medication dosage or stop taking a prescribed drug based on a genetic report. Always discuss your genetic results with your doctor or pharmacist.
Why is the evidence for this variant considered limited?
The evidence is limited because the variant is rare, making it difficult for researchers to conduct large-scale studies. Additionally, some studies have found no significant association between this variant and drug toxicity.
Does this variant cause thiopurine toxicity?
While the NUDT15 gene as a whole is linked to thiopurine toxicity, it is not confirmed that this specific variant (rs186364861) is a primary cause. Research into its specific impact is ongoing.
Sources & further reading
Educational information only, last refreshed 9/30/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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A recurring low-frequency missense variant (p.Val18Ile) defining the NUDT15*2 haplotype, reducing thiopurine tolerance in pediatric leukemia patients.
Splice/intronic regulatory modifier in NUDT15 associated with reduced enzyme level and enhanced susceptibility to thiopurine-induced severe leukopenia.
This missense change (NUDT15 p.Arg139Cys, defining the *3 allele) substantially reduces enzyme activity and confers high risk of life-threatening thiopurine-induced leukopenia.
NUDT15 c.55_56insGAGTCG intermediate-activity allele (defining NUDT15*6), associated with severe thiopurine-induced leukopenia in Asian and Hispanic populations.
Defines the loss-of-function NUDT15*3 allele (p.Arg139Cys), a primary determinant of severe thiopurine-induced leukopenia and myelosuppression.
This variant (NUDT15 *3) is the primary predictor of severe, life-threatening bone marrow toxicity when taking thiopurine drugs.