What you carry at this position in your DNA and what research says about it.
Thiopurine Drug Sensitivity: 9/10 evidence, 61 publications.
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Sample genotype (not yours): C/C
Typical Drug Sensitivity and Normal Enzyme Activity
Normal levels of the ITPA enzyme ensure efficient clearance of abnormal cellular nucleotides. This typical activity protects against toxic side effects when taking thiopurine medications, though it increases the risk of anemia if treated with ribavirin.
What this genotype means: Normal ITPA enzyme activity; Typical tolerance to thiopurine medications; Increased risk of ribavirin-induced anemia.
Sample genotype (not yours): A/A
Enzyme Deficiency and High Thiopurine Sensitivity
Two copies of the variant allele result in a complete lack of functional ITPA enzyme activity. This deficiency causes extreme sensitivity and high risk of toxicity from thiopurine medications, but provides strong protection against ribavirin-induced anemia.
What this genotype means: Complete lack of ITPA enzyme activity; High risk of severe thiopurine drug toxicity; Strong protection against ribavirin-induced anemia.
Sample genotype (not yours): C/A
Reduced Enzyme Activity and Moderate Thiopurine Sensitivity
A single copy of the variant allele reduces ITPA enzyme activity to approximately 25% of normal levels. This reduction moderately increases the risk of toxicity from thiopurine drugs while offering partial protection against ribavirin-induced anemia.
What this genotype means: ITPA enzyme activity reduced to 25%; Moderately increased risk of thiopurine toxicity; Decreased risk of ribavirin-induced anemia.
Gene function and biological role
Gene Function: The ITPA gene encodes inosine triphosphate pyrophosphatase, an essential enzyme responsible for sanitizing the cellular nucleotide pool [1]. It prevents the unwanted accumulation of abnormal purine nucleotides, such as inosine triphosphate, by hydrolyzing them back into safer monophosphate forms [1]. Without adequate activity of this enzyme, these abnormal nucleotides can build up and become incorporated into DNA and RNA, leading to cellular dysfunction or death [2]. This process is particularly critical during the metabolism of certain immunosuppressive and anticancer medications [3].
Variant Impact: The rs1127354 variant is a missense mutation in the ITPA gene that alters the amino acid at position 32 from proline to threonine [2]. This structural change severely impairs the enzyme's ability to bind and break down abnormal nucleotides [2]. Consequently, cellular levels of inosine triphosphate rise significantly, leading to altered drug metabolism and increased sensitivity to specific medications [3]. While this enzyme deficiency is generally harmless under normal conditions, it becomes highly clinically relevant when a person is treated with thiopurine drugs or ribavirin [4].
Key Insight: This variant causes a dramatic loss of enzyme activity that is normally harmless, but becomes a major health factor only when taking specific medications like thiopurines or ribavirin.
Location: ITPA. Chromosome 20 · 20p13 · 3.2 Mb
Estimated prevalence by population
Global 87.6%; European 86.0%; African 91.4%; East Asian 68.2%; South Asian 76.9%; Americas 92.8%; Ashkenazi 86.6%; Finnish 90.6%; Middle Eastern 93.3%; Amish 85.2%.
Estimated CC genotype frequency.
Global 11.9%; European 13.5%; African 8.4%; East Asian 28.7%; South Asian 21.6%; Americas 7.1%; Ashkenazi 12.9%; Finnish 9.2%; Middle Eastern 6.6%; Amish 14.2%.
Estimated CA genotype frequency.
Global 0.5%; European 0.5%; African 0.2%; East Asian 3.0%; South Asian 1.5%; Americas 0.1%; Ashkenazi 0.5%; Finnish 0.2%; Middle Eastern 0.1%; Amish 0.6%.
Estimated AA genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Immunosuppressant & Biologic Response
Thiopurine Toxicity. Evidence: 6/10. Source: PMID 20021291. Typical Risk.
Antimicrobial & Antiviral Response
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20637204. Increased Risk.
Drug Metabolism Enzyme Activity
ITPA Enzyme Activity. Evidence: 8/10. Source: PMID 11278832. Normal Activity.
Showing effects for A/A genotype
Thiopurine Toxicity. Evidence: 6/10. Source: PMID 20021291. High Risk.
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20637204. Low Risk.
ITPA Enzyme Activity. Evidence: 8/10. Source: PMID 11278832. Absent Activity.
Showing effects for C/A genotype
Thiopurine Toxicity. Evidence: 6/10. Source: PMID 20021291. Increased Risk.
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20637204. Decreased Risk.
ITPA Enzyme Activity. Evidence: 8/10. Source: PMID 11278832. 25% Activity.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having the common C/C genotype means the ITPA enzyme functions at full capacity, maintaining a clean cellular nucleotide pool [1]. When treated with thiopurine drugs like azathioprine or mercaptopurine, this normal enzyme activity helps prevent the toxic accumulation of active drug metabolites, resulting in a typical risk of bone marrow suppression [2]. However, during hepatitis C treatment with ribavirin, normal ITPA activity allows the drug to deplete triphosphate pools in red blood cells, significantly increasing the risk of hemolytic anemia [3]. Clinical guidelines suggest that patients with this genotype are less likely to require thiopurine dose reductions but should be closely monitored for anemia if undergoing ribavirin therapy [3].
Normal ITPA enzyme activity; Typical tolerance to thiopurine medications; Increased risk of ribavirin-induced anemia.
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele causes a complete deficiency of the ITPA enzyme, meaning the body cannot clear certain abnormal nucleotides [1]. When exposed to thiopurine drugs like azathioprine or mercaptopurine, the lack of enzyme activity leads to a severe accumulation of toxic metabolites, greatly increasing the risk of life-threatening bone marrow suppression [2]. Because of this high toxicity risk, alternative treatments or drastic dose reductions are typically considered for individuals with this genotype [3]. On the positive side, the complete absence of ITPA activity prevents ribavirin from causing red blood cell destruction, rendering these individuals highly resistant to ribavirin-induced hemolytic anemia [4].
Complete lack of ITPA enzyme activity; High risk of severe thiopurine drug toxicity; Strong protection against ribavirin-induced anemia.
Sample genotype: CA (Heterozygous)
Carrying one copy of the A allele leads to a substantial reduction in ITPA enzyme activity, leaving it at about a quarter of its typical capacity [1]. This partial deficiency alters the breakdown of purine-based medications, which can lead to an accumulation of active metabolites in the body [2]. Consequently, there is a moderately elevated risk of side effects, such as low white blood cell counts or flu-like symptoms, when taking thiopurines like azathioprine [3]. Conversely, this reduced activity helps preserve nucleotide pools in red blood cells during ribavirin therapy, offering significant protection against treatment-induced hemolytic anemia [4].
ITPA enzyme activity reduced to 25%; Moderately increased risk of thiopurine toxicity; Decreased risk of ribavirin-induced anemia.
Variants with shared genetic architecture
rs7270101 · ITPA Gene · Chr 20 · Medication Sensitivity
rs116855232 · NUDT15 Gene · Chr 13 · Thiopurine Toxicity Risk
rs1800462 · TPMT Gene · Chr 6 · Thiopurine Drug Sensitivity
Functional study of the P32T ITPA variant associated with drug sensitivity in humans.
Content updated August 2026.
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