What you carry at this position in your DNA and what research says about it.
Thiopurine Drug Toxicity: 8/10 evidence, 10 publications.
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Sample genotype (not yours): C/C
Normal Drug Metabolism and Typical Toxicity Risk
Standard enzyme activity allows for normal processing of thiopurine medications. Standard doses of these drugs are typically well-tolerated without an elevated risk of bone marrow toxicity.
What this genotype means: Standard thiopurine drug clearance; Typical baseline risk of cisplatin-induced hearing loss.
Sample genotype (not yours): C/T
Intermediate Drug Metabolism and Elevated Toxicity Risk
Reduced enzyme activity slows the clearance of thiopurine medications, which is associated with a higher risk of bone marrow toxicity. TPMT is one of the genes clinical guidelines take into account for these medicines.
What this genotype means: Slower clearance of thiopurine medications; Elevated risk of cisplatin-induced hearing damage.
Sample genotype (not yours): T/T
Poor Drug Metabolism and Severe Toxicity Risk
Complete lack of active enzyme prevents the detoxification of thiopurine medications. Standard doses of these drugs can cause life-threatening bone marrow suppression.
What this genotype means: Severely impaired thiopurine drug clearance; High risk of cisplatin-induced hearing damage.
Gene function and biological role
Gene Function: The TPMT gene encodes thiopurine S-methyltransferase, an enzyme responsible for metabolizing thiopurine drugs. These medications, including azathioprine and mercaptopurine, are commonly used to treat inflammatory bowel disease, autoimmune disorders, and childhood leukemia. Without sufficient TPMT activity, these drugs can build up to toxic levels in the body, leading to severe bone marrow suppression. Genetic variations in this gene are the primary cause of individual differences in drug clearance. Testing for these variants helps clinicians tailor medication dosages to prevent dangerous side effects.
Variant Impact: The rs1800460 variant is a missense mutation in the TPMT gene that changes the amino acid alanine to threonine at position 154. This specific change, known as the TPMT*3B allele, significantly destabilizes the enzyme and leads to its rapid degradation. Consequently, the body's ability to safely process thiopurine medications is severely compromised. In addition to thiopurine sensitivity, this variant has been linked to an increased risk of hearing damage in pediatric cancer patients undergoing cisplatin chemotherapy.
Key Insight: This variant not only impacts how the body processes common immunosuppressants but also increases the risk of permanent hearing loss from cisplatin chemotherapy.
Location: TPMT. Chromosome 6 · 6p22.3 · 18.1 Mb
Estimated prevalence by population
Global 94.9%; European 92.5%; African 98.6%; East Asian 100.0%; South Asian 98.8%; Americas 92.4%; Ashkenazi 96.4%; Finnish 94.8%; Middle Eastern 97.3%; Amish 96.7%.
Estimated CC genotype frequency.
Global 5.0%; European 7.3%; African 1.4%; East Asian 0.0%; South Asian 1.2%; Americas 7.4%; Ashkenazi 3.6%; Finnish 5.2%; Middle Eastern 2.7%; Amish 3.2%.
Estimated CT genotype frequency.
Global 0.1%; European 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas 0.1%; Ashkenazi < 0.1%; Finnish 0.1%; Middle Eastern < 0.1%; Amish < 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 8561894. Typical Risk.
IBD Drug Response. Evidence: 8/10. Source: PMID 22385887. Typical Response.
Chemotherapy Response
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 23588304. Typical Risk.
Leukemia Drug Response. Evidence: 8/10. Source: PMID 18685564. Typical Response.
Showing effects for C/T genotype
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 8561894. Increased Risk.
IBD Drug Response. Evidence: 8/10. Source: PMID 22385887. Impaired Metabolism.
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 23588304. Increased Risk.
Leukemia Drug Response. Evidence: 8/10. Source: PMID 18685564. Impaired Metabolism.
Showing effects for T/T genotype
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 8561894. Severe Risk.
IBD Drug Response. Evidence: 8/10. Source: PMID 22385887. Severe Toxicity Risk.
Leukemia Drug Response. Evidence: 8/10. Source: PMID 18685564. Severe Toxicity Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Normal thiopurine S-methyltransferase activity is maintained by this genotype, ensuring standard clearance of immunosuppressive and chemotherapy drugs. Standard doses of medications like azathioprine or mercaptopurine are processed efficiently, minimizing the risk of severe bone marrow suppression. Clinical guidelines suggest that standard starting doses are appropriate for individuals with this genetic profile. Additionally, the risk of cisplatin-induced hearing loss remains at the typical baseline level. Monitoring remains standard practice during chemotherapy, but no genetically-driven dose reductions are indicated. This common genetic profile is found in the vast majority of the global population.
Standard thiopurine drug clearance; Typical baseline risk of cisplatin-induced hearing loss.
Sample genotype: CT (Heterozygous)
Intermediate thiopurine S-methyltransferase activity results from having one non-functional copy of the gene. Processing of thiopurine drugs is significantly slowed, which can lead to an accumulation of active, toxic metabolites in the bloodstream. Clinical guidelines frequently recommend reducing the starting doses of azathioprine or mercaptopurine by 30% to 70% to avoid severe myelosuppression. There is also an increased risk of permanent hearing loss when undergoing cisplatin chemotherapy, particularly in pediatric patients. Close clinical monitoring of blood counts is standard practice to ensure safety and efficacy. This intermediate profile is present in about 3% to 10% of various populations worldwide.
Slower clearance of thiopurine medications; Elevated risk of cisplatin-induced hearing damage.
Sample genotype: TT (Homozygous)
Extremely low or absent thiopurine S-methyltransferase activity occurs when both copies of the gene are non-functional. Standard doses of thiopurine medications cannot be safely cleared, leading to rapid and severe bone marrow toxicity. Pediatric patients receiving cisplatin chemotherapy also face a significantly heightened risk of permanent hearing damage. This poor metabolizer status is rare, occurring in less than 1% of the population.
Severely impaired thiopurine drug clearance; High risk of cisplatin-induced hearing damage.
Variants with shared genetic architecture
rs1142345 · TPMT Gene · Chr 6 · Thiopurine Drug Sensitivity
rs1800462 · TPMT Gene · Chr 6 · Thiopurine Drug Sensitivity
rs12201199 · TPMT Gene · Chr 6 · Cisplatin Hearing Loss
Content updated August 2026.
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