Inosine triphosphate pyrophosphatase (ITPase)

Inosine triphosphate pyrophosphatase (commonly abbreviated as ITPase) is an enzyme encoded by the ITPA gene in humans and orthologous genes in other species[1][2]. This enzyme performs a critical “house-cleaning” function by hydrolyzing noncanonical purine nucleotides—in particular, inosine triphosphate (ITP), deoxyinosine triphosphate (dITP), xanthosine triphosphate (XTP), and deoxyxanthosine triphosphate (dXTP)—to their monophosphate and pyrophosphate forms, thereby preventing their incorporation into DNA and RNA, which could otherwise result in mutagenesis or disruption of genetic integrity[1][2][3][4]. ITPase is a homodimeric, cytoplasmic enzyme belonging to the HAM1 NTPase protein family and is evolutionarily conserved across all domains of life[1][2][4]. Genetic variants affecting ITPA activity influence the safety and efficacy of drugs such as ribavirin and thiopurines, with consequences for diseases including hepatitis C, cancer, and inherited neurological disorders[1][2]. Deficiency or polymorphism in ITPA can lead to accumulation of toxic noncanonical nucleotides, resulting in increased risk for adverse drug reactions and disease phenotypes[1][2].

Other names

ITPaseITPA (gene)Inosine triphosphataseInosine-5'-triphosphataseHAM1 (yeast ortholog)rdgB (bacterial ortholog)

Hydrolyzes ribavirin triphosphate to monophosphate (impacting drug availability and toxicity[1]) Metabolizes thiopurine drug metabolites, reducing the risk of incorporation into nucleic acids and associated toxicity[2] Protects cells from mutagenesis by removing noncanonical nucleotides