What you carry at this position in your DNA and what research says about it.
Thiopurine Drug Sensitivity: 8/10 evidence, 5 publications.
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Sample genotype (not yours): C/C
Normal Thiopurine Drug Metabolism
You have two functional copies of the TPMT gene, resulting in normal enzyme activity. You can process standard doses of thiopurine medications typically.
What this genotype means: Normal TPMT enzyme activity; Standard response to thiopurine drugs; Typical risk of bone marrow suppression.
Sample genotype (not yours): C/G
Intermediate Thiopurine Drug Metabolism
You carry one non-functional copy of the TPMT gene, which moderately reduces your ability to break down certain drugs. Standard doses of thiopurine medications may cause increased side effects.
What this genotype means: Reduced TPMT enzyme activity; Moderate risk of thiopurine toxicity; May be more sensitive to these drugs.
Sample genotype (not yours): G/G
Severe Thiopurine Drug Sensitivity
You carry two non-functional copies of the TPMT gene, leading to a complete lack of enzyme activity. Standard doses of thiopurine medications can be highly toxic.
What this genotype means: Complete loss of TPMT enzyme activity; High risk of life-threatening toxicity; Severe thiopurine toxicity risk; alternative medication usually needed.
Gene function and biological role
Gene Function: The TPMT gene encodes thiopurine S-methyltransferase, an enzyme crucial for metabolizing thiopurine drugs. These medications, including azathioprine and mercaptopurine, are widely used to treat autoimmune diseases, inflammatory bowel disease, and certain leukemias. The enzyme inactivates these drugs by transferring a methyl group, preventing them from turning into highly toxic metabolites. When TPMT activity is compromised, active drug metabolites accumulate in the body and attack healthy tissues. This process primarily targets the bone marrow, leading to severe drops in blood cell counts. Understanding TPMT genetics is a standard clinical practice to ensure safe drug dosing.
Variant Impact: A single nucleotide substitution at rs1800462 creates a missense mutation in the TPMT gene, resulting in an alanine-to-proline substitution at codon 80 (p.Ala80Pro). This specific molecular change is designated as the TPMT*2 allele, which is one of the primary non-functional alleles of the gene. The proline substitution alters the structure of the enzyme, making it highly unstable and prone to rapid degradation. Consequently, the resulting protein has a near-complete loss of catalytic activity. This variant is relatively rare but has profound clinical implications for drug safety.
Key Insight: A single letter change in this gene can cause a 100-fold drop in the enzyme's ability to break down certain medications. While extremely rare globally, carrying two copies of this variant makes standard doses of common immunosuppressants highly toxic.
Location: TPMT. Chromosome 6 · 6p22.3 · 18.1 Mb
Estimated prevalence by population
Global 99.6%; European 99.5%; African 99.9%; East Asian > 99.9%; South Asian 100.0%; Americas 98.6%; Ashkenazi 99.7%; Finnish 100.0%; Middle Eastern 100.0%; Amish 99.8%.
Estimated CC genotype frequency.
Global 0.4%; European 0.5%; African 0.1%; East Asian < 0.1%; South Asian 0.0%; Americas 1.4%; Ashkenazi 0.3%; Finnish 0.0%; Middle Eastern 0.0%; Amish 0.2%.
Estimated CG genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian < 0.1%; South Asian 0.0%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish 0.0%; Middle Eastern 0.0%; Amish < 0.1%.
Estimated GG genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 22385887. Typical Sensitivity.
Drug Metabolism Enzyme Activity
TPMT Enzyme Activity. Evidence: 8/10. Source: PMID 22385887. Normal Activity.
Showing effects for C/G genotype
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 22385887. Increased Sensitivity.
TPMT Enzyme Activity. Evidence: 8/10. Source: PMID 22385887. Intermediate Activity.
Showing effects for G/G genotype
Thiopurine Sensitivity. Evidence: 8/10. Source: PMID 22385887. Severe Sensitivity.
TPMT Enzyme Activity. Evidence: 8/10. Source: PMID 22385887. No Activity.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Normal thiopurine S-methyltransferase function is represented by this common global genotype. With two fully active copies of the TPMT gene, the body efficiently inactivates thiopurine drugs like azathioprine and mercaptopurine. Efficient clearance prevents the toxic buildup of active drug metabolites in the bloodstream. Consequently, if these medications are ever required for conditions like inflammatory bowel disease or leukemia, the risk for severe bone marrow toxicity remains low. Standard dosing guidelines generally apply to this genetic profile. No special genetic precautions are typically needed for thiopurine therapy based on this variant alone. Most people in the general population share this typical metabolic capacity.
Normal TPMT enzyme activity; Standard response to thiopurine drugs; Typical risk of bone marrow suppression.
Sample genotype: CG (Heterozygous)
Intermediate enzyme activity results from carrying one non-functional TPMT*2 allele. A single functional copy of the gene reduces the body's capacity to methylate and clear thiopurine drugs. Standard doses of medications like azathioprine or mercaptopurine can lead to a moderate accumulation of active, toxic metabolites. This accumulation increases the risk of developing myelosuppression, a condition where bone marrow activity decreases. Clinical guidelines often recommend starting with reduced doses of these medications to prevent toxicity. Regular blood counts are typically performed to monitor for adverse reactions during treatment. Knowing this status helps healthcare providers tailor drug therapies safely.
Reduced TPMT enzyme activity; Moderate risk of thiopurine toxicity; May be more sensitive to these drugs.
Sample genotype: GG (Homozygous)
A complete deficiency of the TPMT enzyme occurs in those with two copies of the TPMT*2 non-functional allele. Without any active enzyme, the body is unable to safely process and clear thiopurine medications. Standard doses of drugs like azathioprine or mercaptopurine will cause rapid, extreme accumulation of cytotoxic metabolites. This buildup can lead to severe, life-threatening bone marrow suppression and profound cytopenias. Clinical guidelines treat this as a severe thiopurine toxicity risk and generally call for an alternative medication or a substantially reduced regimen. Genetic testing for this variant is highly valuable before initiating thiopurine therapy to prevent severe adverse events. Discussing these findings with a doctor is critical if thiopurines are ever prescribed.
Complete loss of TPMT enzyme activity; High risk of life-threatening toxicity; Severe thiopurine toxicity risk; alternative medication usually needed.
Variants with shared genetic architecture
rs1142345 · TPMT Gene · Chr 6 · Thiopurine Drug Sensitivity
rs1800460 · TPMT Gene · Chr 6 · Thiopurine Drug Toxicity
rs12201199 · TPMT Gene · Chr 6 · Cisplatin Hearing Loss
Content updated August 2026.
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