TPMT rs386621910: Understanding Genetic Metabolic Variation
The rs386621910 variant is a rare genetic change located within the TPMT gene, which encodes an enzyme responsible for processing specific medications. This variant is studied in the context of pharmacogenomics to understand how individual genetic differences may influence the body's ability to metabolize thiopurine drugs.
What each genotype means
Normal metabolizer
This genotype is associated with normal TPMT enzyme activity. Individuals with this genotype typically metabolize thiopurine medications at a standard rate, and no dose adjustments are typically recommended based solely on this genotype.
Carried by approximately 86-97% of individuals, making it the most common genotype.
Intermediate metabolizer
This genotype indicates intermediate TPMT enzyme activity, meaning the enzyme's function is reduced. Individuals with this genotype may experience decreased metabolism of thiopurine medications, potentially leading to increased drug levels and a higher risk of side effects; please discuss potential medication dosing with your clinician or pharmacist.
Carried by approximately 3-14% of individuals, with about 11% of the population showing intermediate TPMT activity.
Poor metabolizer
This genotype is associated with significantly reduced or absent TPMT enzyme activity. Individuals with this genotype are at a very high risk of experiencing severe toxicity when treated with standard doses of thiopurine medications, so please discuss potential medication dosing or alternative therapies with your clinician or pharmacist.
Carried by approximately 0.3% of individuals, with about 1 in 300 people having TPMT deficiency.
What is rs386621910 and Where is it Located?
The rs386621910 variant is a specific single nucleotide polymorphism (SNP) found within the TPMT gene. The TPMT gene is located on chromosome 6p22.3 and consists of 10 exons. This gene provides instructions for creating the thiopurine S-methyltransferase enzyme. In the field of genetics, rs386621910 serves as a marker that researchers track to identify variations in the DNA sequence that might alter the structure or function of the resulting protein. Because this variant is relatively rare, it is often identified through targeted sequencing or large-scale genomic studies rather than being a common feature in the general population. Understanding its location within the gene is critical for scientists, as variants in different regions of the TPMT gene can have varying impacts on how the enzyme is produced or how effectively it functions in the body.
The Role of the TPMT Gene
The TPMT gene is essential for the metabolism of thiopurine drugs, which are a class of medications often used to treat conditions like inflammatory bowel disease, leukemia, and autoimmune disorders. The enzyme produced by this gene, thiopurine S-methyltransferase, helps break down these drugs into inactive metabolites. When the TPMT enzyme functions normally, it prevents the accumulation of toxic levels of these medications in the blood. However, genetic variations can lead to reduced enzyme activity. If an individual has lower-than-normal TPMT activity, they may be at a higher risk for side effects, such as myelosuppression, because the drugs remain active in the body for longer than intended. Conversely, very high activity might lead to sub-therapeutic drug levels. Because of this, the TPMT gene is a primary focus of pharmacogenomic research, which aims to tailor drug dosages based on an individual's unique genetic profile.
Research Associations and Evidence Strength
Research into rs386621910 is currently categorized as having limited evidence regarding its specific clinical impact. While many variants in the TPMT gene, such as *2, *3A, and *3C, are well-documented and have established clinical guidelines for dose adjustments, rs386621910 is less frequently characterized in large-scale clinical trials. Current scientific literature focuses on identifying how such rare variants correlate with enzyme activity levels. Because the evidence is limited, it is not yet standard practice to use this specific variant as a primary indicator for clinical decision-making in the same way clinicians use more common, well-studied alleles. Researchers continue to investigate whether this variant contributes to the trimodal distribution of enzyme activity—normal, intermediate, and low—observed in various populations. As more data becomes available, the clinical understanding of this variant may evolve, but for now, it remains a subject of ongoing scientific inquiry rather than a definitive diagnostic marker.
Population Frequency and Distribution
The rs386621910 variant is classified as rare across most global populations. In genomics, a variant is considered rare if it appears in a very small percentage of the population. Unlike the more common TPMT variants that are found in a significant portion of individuals of European or African descent, rs386621910 does not appear at high frequencies in standard reference databases. This rarity makes it challenging for researchers to gather enough data to draw definitive conclusions about its functional consequences. Because it is not a common polymorphism, most individuals will not carry this specific variant. When it is detected, it is often found in the context of specialized genetic testing or research studies aimed at uncovering the full spectrum of human genetic diversity. Its low frequency underscores the importance of large-scale genomic sequencing to identify and understand the rare variants that may still play a role in individual drug responses.
What You Can and Cannot Do With This Information
If you have received information about your status for rs386621910, it is important to understand the limitations of this data. You cannot use this information to diagnose a condition or predict a guaranteed reaction to a medication. Because the evidence for this specific variant is limited, it does not currently dictate standard clinical dosing protocols in the same way that established TPMT variants do. You should never change your medication dosage or stop taking a prescribed drug based on genetic test results without consulting your healthcare provider. Instead, use this information as a starting point for a conversation with your doctor or a clinical pharmacist. They can interpret your genetic report in the context of your overall health, current medications, and other clinical factors. Pharmacogenomics is a complex field, and professional medical guidance is essential to ensure that any decisions regarding your treatment are safe, effective, and based on the most current clinical evidence.
How common is this variant?
The rs386621910 variant is considered rare in the general population, with low minor allele frequencies observed across most ancestral groups.
Frequently asked questions
What is the TPMT gene used for?
The TPMT gene provides instructions for making an enzyme that helps break down thiopurine drugs. These medications are often used to treat conditions like inflammatory bowel disease and certain types of cancer.
Should I get tested for TPMT variants?
Pharmacogenomic testing for TPMT is often recommended before starting thiopurine therapy to help clinicians determine the safest starting dose. You should discuss the necessity of this testing with your doctor based on your specific treatment plan.
Does having a TPMT variant mean I cannot take thiopurines?
Not necessarily. If a patient has a variant that reduces enzyme activity, doctors may simply adjust the dosage or monitor the patient more closely. Always consult your clinician before making any changes to your medication.
Where can I find more information about my specific genotype?
You can discuss your genetic report with a genetic counselor or your prescribing physician. They can help interpret the results in the context of your medical history and current clinical guidelines.
Sources & further reading
Educational information only, last refreshed 9/22/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs386621910?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in TPMT
Defines the TPMT*4 splice-site mutation (c.414+1G>A) causing complete inactivation of thiopurine methyltransferase and severe toxicity.
Defines the non-functional TPMT*2 missense allele (c.238G>C, p.Ala80Pro), which confers significantly impaired thiopurine metabolism and heightened risk of life-threatening myelosuppression with azathioprine or mercaptopurine.
The rs1800460 variant defines the TPMT*3B allele, and in cis with rs1142345, forms the TPMT*3A haplotype conferring deficient thiopurine methyltransferase activity.
The TPMT*3C variant is a major determinant of thiopurine metabolism, associated with reduced enzyme activity.
This missense variant in the TPMT gene is associated with altered thiopurine metabolism and is considered a rare variant in global populations.
Variant in TPMT associated with thiopurine metabolism; clinical testing is recommended for patients starting thiopurine therapy.