ITPA
Description
The ITPA (inosine triphosphatase) is a protein-coding gene located on chromosome 20.
ITPA is an enzyme encoded by the ITPA gene in humans, rdgB in bacteria E. coli, and HAM1 in yeast S. cerevisiae. Some RNA viruses from the Potyviridae family also encode this protein. Two transcript variants leading to two distinct isoforms have been identified for this gene. Additionally, at least two other transcript variants, likely regulatory rather than protein-coding, have been discovered. ITPA hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. It exhibits broad substrate specificity, acting on other nucleotides including xanthosine triphosphate and deoxyxanthosine triphosphate. ITPA, a member of the HAM1 NTPase protein family, resides in the cytoplasm and functions as a homodimer. Deficiencies in ITPA can cause inosine triphosphate pyrophosphorylase deficiency. ITPA dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate. Reduced ITPA activity, present in 30% of humans, can enhance mutagenesis in hepatitis C virus. Gene variants predicting decreased ITPA activity have been linked to a reduced risk of ribavirin-induced anemia, an increased risk of thrombocytopenia, lower ribavirin concentrations, and a ribavirin-like reduced relapse risk following interferon-based therapy for hepatitis C virus (HCV) genotype 2 or 3 infection.
ITPA hydrolyzes non-canonical purine nucleotides like inosine triphosphate (ITP), deoxyinosine triphosphate (dITP), 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP), and xanthosine 5'-triphosphate (XTP) into their monophosphate forms. It doesn't differentiate between deoxy- and ribose forms. ITPA likely prevents these non-canonical purines from entering RNA and DNA precursor pools, thus hindering their incorporation into RNA and DNA and preventing chromosomal damage.
ITPA is also known as C20orf37, DEE35, HLC14-06-P, ITPase, My049, NTPase, dJ794I6.3.
