What you carry at this position in your DNA and what research says about it.
Thiopurine Drug Sensitivity: 9/10 evidence, 18 publications.
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Sample genotype (not yours): T/T
Typical Thiopurine Drug Metabolism
Normal TPMT enzyme activity means standard doses of thiopurine medications are processed as expected. There is no elevated genetic risk of severe toxicity from these specific drugs.
What this genotype means: Normal processing of thiopurine medications; Typical risk of chemotherapy-induced side effects.
Sample genotype (not yours): C/C
Severely Impaired Thiopurine Metabolism
Carrying two copies of the variant leads to a complete lack of functional TPMT enzyme. Standard doses of thiopurine drugs can cause life-threatening bone marrow toxicity.
What this genotype means: Severe deficiency in thiopurine clearance; Extremely high risk of life-threatening bone marrow toxicity; High risk of cisplatin-induced hearing loss.
Sample genotype (not yours): T/C
Intermediate Thiopurine Metabolism
Carrying one copy of the variant reduces TPMT enzyme activity, increasing the risk of drug toxicity. Standard doses of thiopurine medications may cause severe side effects like bone marrow suppression.
What this genotype means: Reduced ability to clear thiopurine drugs; Higher risk of bone marrow toxicity; Increased risk of cisplatin-induced hearing damage.
Gene function and biological role
Gene Function: The TPMT gene encodes thiopurine S-methyltransferase, an enzyme crucial for metabolizing thiopurine drugs [1]. These medications, including azathioprine and mercaptopurine, are commonly used to treat leukemia, inflammatory bowel disease, and autoimmune disorders [2]. The enzyme acts as a primary pathway to break down these drugs into harmless compounds [1]. When TPMT activity is low, active drug metabolites can build up to toxic levels, damaging the bone marrow [2]. This makes TPMT one of the most well-established genes in clinical pharmacogenomics [1].
Variant Impact: This variant, rs1142345, is a missense mutation that changes the amino acid tyrosine to cysteine at position 240 of the TPMT protein [3]. This specific change, known as the TPMT*3C allele, destabilizes the enzyme and leads to rapid protein degradation [2]. As a result, individuals carrying this variant have significantly reduced or absent TPMT enzymatic activity [3]. This impairment directly hinders the body's ability to safely process thiopurine medications [2]. It also influences susceptibility to toxic side effects from other chemotherapies, such as cisplatin [4].
This variant is also linked to an increased risk of permanent hearing loss from cisplatin chemotherapy.
Location: TPMT. Chromosome 6 · 6p22.3 · 18.1 Mb
Estimated prevalence by population
Global 91.6%; European 91.7%; African 89.3%; East Asian 97.3%; South Asian 96.3%; Americas 90.2%; Ashkenazi 96.2%; Finnish 94.2%; Middle Eastern 96.6%; Amish 96.7%.
Estimated TT genotype frequency.
Global 8.2%; European 8.1%; African 10.4%; East Asian 2.7%; South Asian 3.7%; Americas 9.6%; Ashkenazi 3.7%; Finnish 5.7%; Middle Eastern 3.3%; Amish 3.2%.
Estimated TC genotype frequency.
Global 0.2%; European 0.2%; African 0.3%; East Asian < 0.1%; South Asian < 0.1%; Americas 0.3%; Ashkenazi < 0.1%; Finnish 0.1%; Middle Eastern < 0.1%; Amish < 0.1%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Thiopurine Sensitivity. Evidence: 9/10. Source: PMID 27564568. Typical Sensitivity.
Methotrexate Toxicity. Evidence: 8/10. Source: PMID 22846425. Typical Risk.
Chemotherapy Response
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 23588304. Typical Risk.
Chemotherapy Liver Damage. Evidence: 6/10. Source: PMID 36580335. Typical Risk.
Lifestyle, Fitness & Aging
Aging & Longevity
Biological Aging. Evidence: 5/10. Source: PMID 34187551. Typical Rate.
Showing effects for C/C genotype
Thiopurine Sensitivity. Evidence: 9/10. Source: PMID 27564568. Severe Sensitivity.
Methotrexate Toxicity. Evidence: 8/10. Source: PMID 22846425. Increased Risk.
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 23588304. High Risk.
Chemotherapy Liver Damage. Evidence: 6/10. Source: PMID 36580335. Lower Risk.
Biological Aging. Evidence: 5/10. Source: PMID 34187551. Slower.
Showing effects for T/C genotype
Thiopurine Sensitivity. Evidence: 9/10. Source: PMID 27564568. Increased Sensitivity.
Cisplatin Hearing Loss. Evidence: 6/10. Source: PMID 23588304. Increased Risk.
Biological Aging. Evidence: 5/10. Source: PMID 34187551. Slightly Slower.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Normal TPMT activity is the baseline state for most of the population [1]. Individuals with this genotype typically process thiopurine drugs like azathioprine and mercaptopurine efficiently, avoiding the dangerous accumulation of toxic byproducts [2]. Standard dosing guidelines generally apply, as the body can clear these medications normally [1]. However, other genetic or clinical factors can still influence overall drug response and side effects [2]. There is also no elevated genetic risk of hearing loss from cisplatin chemotherapy associated with this specific locus [3].
Normal processing of thiopurine medications; Typical risk of chemotherapy-induced side effects.
Sample genotype: CC (Homozygous)
This genotype represents a complete or near-complete deficiency in TPMT enzyme activity [1]. Standard doses of thiopurines like azathioprine or mercaptopurine lead to extreme accumulation of active metabolites, causing profound bone marrow suppression [2]. This can result in life-threatening infections or bleeding due to a lack of blood cells [3]. Clinical guidelines suggest drastically reducing thiopurine doses or using alternative therapies [1]. There is also a significantly elevated risk of permanent hearing loss if treated with cisplatin chemotherapy [4].
Severe deficiency in thiopurine clearance; Extremely high risk of life-threatening bone marrow toxicity; High risk of cisplatin-induced hearing loss.
Sample genotype: TC (Heterozygous)
This genotype represents the TPMT*3C intermediate metabolizer status, where enzyme activity is significantly reduced [1]. When treated with standard doses of thiopurines, active drug metabolites can accumulate to dangerous levels in the body [2]. This increases the risk of severe myelosuppression, which is a life-threatening drop in blood cell counts [3]. Additionally, there is an increased risk of hearing damage when undergoing cisplatin chemotherapy [4].
Reduced ability to clear thiopurine drugs; Higher risk of bone marrow toxicity; Increased risk of cisplatin-induced hearing damage.
Variants with shared genetic architecture
rs1800460 · TPMT Gene · Chr 6 · Thiopurine Drug Toxicity
rs1800462 · TPMT Gene · Chr 6 · Thiopurine Drug Sensitivity
rs12201199 · TPMT Gene · Chr 6 · Cisplatin Hearing Loss
Content updated August 2026.
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