What you carry at this position in your DNA and what research says about it.
Medication Sensitivity: 9/10 evidence, 27 publications.
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Sample genotype (not yours): A/A
Typical Drug Response and Higher Ribavirin Anemia Risk
Standard processing of thiopurine medications occurs with this profile due to normal enzyme activity. However, there is an increased risk of developing hemolytic anemia if treated with ribavirin for hepatitis C.
What this genotype means: Normal ITPase enzyme activity; Standard risk of thiopurine side effects; Higher risk of ribavirin-induced anemia.
Sample genotype (not yours): A/C
Protected from Ribavirin Anemia but Sensitive to Thiopurines
Partial enzyme deficiency shields red blood cells from ribavirin-induced anemia during hepatitis C treatment. However, it simultaneously increases the risk of side effects and bone marrow suppression when taking thiopurine drugs.
What this genotype means: Reduced ITPase enzyme activity; Decreased risk of ribavirin-induced anemia; Increased risk of thiopurine drug toxicity.
Sample genotype (not yours): C/C
Highly Protected from Ribavirin Anemia but High Thiopurine Sensitivity
Severe enzyme deficiency offers robust protection against ribavirin-induced anemia. However, it significantly increases the risk of severe bone marrow toxicity when taking thiopurine medications.
What this genotype means: Severe ITPase enzyme deficiency; Strong protection against ribavirin-induced anemia; High risk of severe thiopurine and methotrexate toxicity.
Gene function and biological role
Gene Function: The ITPA gene encodes the inosine triphosphate pyrophosphatase (ITPase) enzyme, which plays a critical role in cellular homeostasis [1]. It acts as a cellular housekeeper by hydrolyzing abnormal nucleotides like inosine triphosphate (ITP) to prevent them from being incorporated into DNA and RNA [1]. When ITPA activity is reduced or absent, these non-standard nucleotides accumulate within cells, particularly in red blood cells [2]. This accumulation can alter cellular energy levels and influence how the body processes certain medications [2]. In particular, ITPA activity levels are a major determinant of how patients respond to antiviral and immunosuppressive therapies [3].
Variant Impact: The rs7270101 variant is a splice-site alteration located in intron 2 of the ITPA gene [1]. This genetic change disrupts normal splicing, leading to a significant reduction in the expression and stability of the ITPase enzyme [1]. Individuals carrying the variant C allele experience a genotype-dependent decrease in ITPase activity, with two copies causing a severe deficiency [1]. This enzyme deficiency alters nucleotide pools in red blood cells, which unexpectedly protects them from ribavirin-induced destruction [2]. However, the same deficiency impairs the clearance of thiopurine drugs, leading to an increased risk of bone marrow toxicity [3].
Key Insight: An enzyme deficiency caused by this variant actually protects red blood cells from being destroyed by hepatitis C antiviral therapy, but it simultaneously makes the body highly sensitive to certain leukemia and autoimmune drugs.
Location: ITPA. Chromosome 20 · 20p13 · 3.2 Mb
Estimated prevalence by population
Global 81.9%; European 75.8%; African 86.0%; East Asian 99.8%; South Asian 95.1%; Americas 82.4%; Ashkenazi 84.5%; Finnish 87.5%; Middle Eastern 83.7%; Amish 95.6%.
Estimated AA genotype frequency.
Global 17.1%; European 22.5%; African 13.5%; East Asian 0.2%; South Asian 4.8%; Americas 16.8%; Ashkenazi 14.8%; Finnish 12.1%; Middle Eastern 15.6%; Amish 4.3%.
Estimated AC genotype frequency.
Global 1.0%; European 1.7%; African 0.5%; East Asian < 0.1%; South Asian 0.1%; Americas 0.9%; Ashkenazi 0.6%; Finnish 0.4%; Middle Eastern 0.7%; Amish < 0.1%.
Estimated CC genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Antimicrobial & Antiviral Response
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20173735. Increased Risk.
Immunosuppressant & Biologic Response
Azathioprine Response. Evidence: 5/10. Source: PMID 18662289. Typical Risk.
Mercaptopurine Toxicity. Evidence: 5/10. Source: PMID 18662289. Typical Risk.
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 26237184. Typical Risk.
Showing effects for A/C genotype
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20173735. Protected.
Azathioprine Response. Evidence: 5/10. Source: PMID 18662289. Increased Risk.
Mercaptopurine Toxicity. Evidence: 5/10. Source: PMID 18662289. Increased Risk.
Showing effects for C/C genotype
Ribavirin Anemia Risk. Evidence: 9/10. Source: PMID 20173735. Highly Protected.
Azathioprine Response. Evidence: 5/10. Source: PMID 18662289. High Risk.
Mercaptopurine Toxicity. Evidence: 5/10. Source: PMID 18662289. High Risk.
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 26237184. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Normal inosine triphosphatase (ITPase) enzyme activity is characteristic of this genetic profile [1]. Because the enzyme functions at full capacity, there is no accumulation of abnormal nucleotides in red blood cells [1]. When undergoing antiviral therapy for chronic hepatitis C using ribavirin and peginterferon, individuals with this genotype have an increased risk of developing hemolytic anemia [2]. Studies show that up to 80% of patients with normal ITPA activity experience significant hemoglobin declines during this treatment [3]. Conversely, normal enzyme activity is highly favorable when taking thiopurine medications like azathioprine or mercaptopurine [4]. These drugs, commonly used for autoimmune conditions and leukemia, are metabolized safely without an elevated risk of bone marrow suppression [4]. No special dosage adjustments are typically indicated based on this genetic locus alone.
Normal ITPase enzyme activity; Standard risk of thiopurine side effects; Higher risk of ribavirin-induced anemia.
Sample genotype: AC (Heterozygous)
A moderate reduction in inosine triphosphatase (ITPase) enzyme activity occurs with one copy of the variant allele [1]. This partial deficiency alters nucleotide levels in red blood cells, which unexpectedly shields them from the destructive effects of ribavirin [2]. During hepatitis C treatment, individuals with this genotype are significantly protected against severe hemolytic anemia and are less likely to require ribavirin dose reductions [2]. However, this same enzyme deficit slows the safe clearance of thiopurine drugs like azathioprine and mercaptopurine [3]. As a result, there is an increased risk of drug toxicity, including low platelet counts and bone marrow suppression [3]. Clinical guidelines suggest that patients requiring thiopurines may benefit from alternative therapies or careful monitoring [3]. This genotype represents a classic genetic trade-off between antiviral protection and immunosuppressive sensitivity.
Reduced ITPase enzyme activity; Decreased risk of ribavirin-induced anemia; Increased risk of thiopurine drug toxicity.
Sample genotype: CC (Homozygous)
Profound deficiency in the inosine triphosphatase (ITPase) enzyme results from carrying two copies of the variant allele [1]. This severe deficiency prevents the depletion of adenosine triphosphate (ATP) in red blood cells during ribavirin therapy [2]. Consequently, this genotype provides robust, near-complete protection against ribavirin-induced hemolytic anemia during hepatitis C treatment [2]. However, the lack of functional enzyme severely compromises the body's ability to process thiopurine medications safely [3]. When exposed to drugs like azathioprine, mercaptopurine, or methotrexate, there is a very high risk of severe bone marrow toxicity, neutropenia, and dangerously low white blood cell counts. Healthcare providers often consider alternative medications or substantial dose reductions when thiopurines are prescribed to individuals with this profile [3]. Knowing this genetic status is highly valuable before starting any of these specific drug regimens.
Severe ITPase enzyme deficiency; Strong protection against ribavirin-induced anemia; High risk of severe thiopurine and methotrexate toxicity.
Variants with shared genetic architecture
rs1127354 · ITPA Gene · Chr 20 · Thiopurine Drug Sensitivity
rs11549407 · HBB Gene · Chr 11 · Thalassemia and Anemia Risk
rs2075672 · TFR2 Gene · Chr 7 · Iron and Blood Health
Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency.
Content updated August 2026.
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