ITPA cDNA Clone – Inosine Triphosphatase (Nucleoside Triphosphate Pyrophosphatase) (Human)

This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ITPA: Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD). It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme. Belongs to the HAM1 NTPase family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: EC 3.6.1.19; Hydrolase; Nucleotide Metabolism - pyrimidine; Nucleotide Metabolism - purine; Xenobiotic Metabolism - drug metabolism - other enzymes

Chromosomal Location of Human Ortholog: 20p

Cellular Component: cytoplasm; cytosol

Biological Process: nucleobase, nucleoside and nucleotide metabolic process

Disease: Epileptic Encephalopathy, Early Infantile, 35; Inosine Triphosphatase Deficiency