TPMT rs1142345: What Your Genotype Means
The rs1142345 variant is a genetic change in the TPMT gene that influences how the body processes certain medications known as thiopurines. Individuals carrying this variant may have reduced enzyme activity, which can impact the safety and effectiveness of treatments for conditions like leukemia and inflammatory bowel disease.
What each genotype means
Normal enzyme activity
This genotype is associated with normal thiopurine S-methyltransferase (TPMT) enzyme activity. Individuals with this profile typically metabolize thiopurine medications 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.
Reduced enzyme activity
This genotype, which corresponds to the TPMT*3C variant, is associated with reduced TPMT enzyme activity. You may metabolize thiopurine medications more slowly than average, which can increase the risk of side effects like myelosuppression. Please discuss your medication dosing and monitoring with your clinician or pharmacist.
This genotype is more common in East Asian and African populations and less common in European populations.
Low or no enzyme activity
This genotype is associated with significantly reduced or absent TPMT enzyme activity. Individuals with this profile are at a higher risk for severe side effects, such as myelosuppression, when taking standard doses of thiopurine medications. It is essential to discuss your medication management and potential alternative dosing strategies with your clinician or pharmacist.
This genotype is rare across most populations, though it is more frequently observed in groups where the TPMT*3C allele is more prevalent.
Understanding the rs1142345 Variant
The rs1142345 variant is a single nucleotide polymorphism (SNP) located within the TPMT gene, which sits on chromosome 6. In scientific literature, this specific genetic change is often referred to as the TPMT*3C allele. At the molecular level, this variant involves a substitution where an adenine is replaced by a guanine, leading to an amino acid change from tyrosine to cysteine at position 240 of the protein. This structural alteration is significant because it affects the stability and function of the resulting enzyme. Because the TPMT gene is responsible for producing an enzyme that breaks down thiopurine drugs, changes in its sequence can lead to variations in how quickly or slowly these medications are cleared from the body. Researchers track this variant closely because it serves as a key marker for predicting how a patient might respond to specific therapeutic regimens.
The Role of the TPMT Gene
The TPMT gene encodes the thiopurine S-methyltransferase enzyme. This enzyme plays a critical role in the metabolic pathway of thiopurine drugs, such as mercaptopurine, azathioprine, and thioguanine. These medications are frequently used as immunosuppressants or chemotherapy agents to treat conditions like acute lymphoblastic leukemia (ALL) and inflammatory bowel disease. Under normal conditions, the TPMT enzyme helps convert these drugs into inactive metabolites, preventing them from accumulating to toxic levels in the body. When the TPMT gene carries variants like rs1142345, the enzyme may be produced in lower quantities or be less stable, leading to reduced enzymatic activity. If a patient with reduced TPMT activity receives a standard dose of a thiopurine medication, the drug may build up in their system, potentially increasing the risk of severe side effects, such as myelosuppression, where the bone marrow produces fewer blood cells.
Research and Clinical Evidence
The evidence linking the rs1142345 variant to altered drug metabolism is considered strong within the field of pharmacogenomics. Numerous studies have demonstrated that individuals with this variant exhibit decreased TPMT enzyme activity compared to those without it. Clinical research has specifically highlighted that patients carrying the *3C allele are at a higher risk for adverse reactions when treated with thiopurines. For instance, some studies have observed associations between this variant and an increased risk of toxicity or complications during the treatment of childhood leukemia. Because of these findings, clinical guidelines often recommend that healthcare providers consider a patient's TPMT genotype or enzyme activity levels before initiating thiopurine therapy. This personalized approach aims to optimize dosing, ensuring that patients receive the therapeutic benefit of the medication while minimizing the risk of dangerous side effects. Always consult with your clinician or pharmacist to discuss how your genetic information may relate to your specific treatment plan.
What You Can Do With This Information
Genetic information regarding the rs1142345 variant is a tool for informed health discussions, not a standalone diagnostic result. If you have received testing that identifies this variant, it is important to share this information with your healthcare provider, especially if you are prescribed or are currently taking thiopurine medications. Your doctor or pharmacist can interpret these results in the context of your overall health, medical history, and other medications you may be taking. They may use this information to adjust your dosage or select alternative therapies to ensure your treatment is both safe and effective. It is crucial to remember that genetic variants are only one factor in how your body responds to drugs; environmental factors, diet, and other genes also play a role. Never make changes to your medication regimen based on genetic test results without professional medical guidance.
How common is this variant?
The rs1142345 variant is common in East Asian and African populations, where it is a primary cause of reduced TPMT activity, while it is less frequently observed in European populations.
Frequently asked questions
What is the TPMT gene?
The TPMT gene provides instructions for making an enzyme called thiopurine S-methyltransferase. This enzyme is responsible for breaking down certain drugs used to treat cancer and autoimmune diseases.
Why is rs1142345 important for medication?
This variant can lead to lower levels of the TPMT enzyme. If a person has low enzyme activity, thiopurine medications may build up in the body, increasing the risk of side effects.
Does having this variant mean I cannot take thiopurines?
Not necessarily. If a patient has this variant, doctors may simply adjust the dosage of the medication to a safer level or monitor the patient more closely during treatment.
Should I get tested for TPMT variants?
Testing is often recommended by clinical guidelines before starting thiopurine therapy. You should discuss the necessity and implications of this testing with your healthcare provider.
Sources & further reading
Educational information only, last refreshed 9/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Defines the TPMT*4 splice-site mutation (c.414+1G>A) causing complete inactivation of thiopurine methyltransferase and severe toxicity.
A rare variant in the TPMT gene associated with metabolic processing.
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.
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.