ITPA

Inosine triphosphate pyrophosphatase is an enzyme that in humans is encoded by the ITPA gene,^[5][6] by the rdgB gene in bacteria E.coli^[7] and the HAM1 gene in yeast S. cerevisiae;^[8] the protein is also encoded by some RNA viruses of the Potyviridae family.^[9] Two transcript variants encoding two different isoforms have been found for this gene. Also, at least two other transcript variants have been identified which are probably regulatory rather than protein-coding.^{[citation needed]}

ITPA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CAR, 2I5D, 2J4E, 4F95
Identifiers
Aliases	ITPA, C20orf37, HLC14-06-P, dJ794I6.3, My049, ITPase, NTPase, inosine triphosphatase, DEE35
External IDs	OMIM: 147520; MGI: 96622; HomoloGene: 6289; GeneCards: ITPA; OMA:ITPA - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20p13 Start 3,208,868 bp[1] End 3,223,870 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 F1|2 63.24 cM Start 130,509,530 bp[2] End 130,523,534 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland mucosa of transverse colon right adrenal cortex right uterine tube left adrenal gland left adrenal cortex mucosa of esophagus granulocyte skin of leg Top expressed in embryo embryo ventricular zone endocardial cushion epiblast primitive streak morula ganglionic eminence neural tube otic placode More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding dITP diphosphatase activity XTP diphosphatase activity ITP diphosphatase activity hydrolase activity metal ion binding nucleotide diphosphatase activity NADH pyrophosphatase activity nucleoside-triphosphate diphosphatase activity identical protein binding Cellular component cytoplasm cytosol Biological process ITP catabolic process nucleotide metabolic process chromosome organization nucleoside triphosphate catabolic process purine nucleotide catabolic process deoxyribonucleoside triphosphate catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3704 16434 Ensembl ENSG00000125877 ENSMUSG00000074797 UniProt Q9BY32 Q9D892 RefSeq (mRNA) NM_001267623 NM_033453 NM_181493 NM_001324236 NM_001324237 NM_001324238 NM_001324240 NM_001351739 NM_025922 NM_001362648 RefSeq (protein) NP_001254552 NP_001311165 NP_001311166 NP_001311167 NP_001311169 NP_258412 NP_852470 NP_001338668 NP_080198 NP_001349577 Location (UCSC) Chr 20: 3.21 – 3.22 Mb Chr 2: 130.51 – 130.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate.^[6] The enzyme possesses specificity to multiple substrates, and acts on other nucleotides including xanthosine triphosphate and deoxyxanthosine triphosphate.^[8] The encoded protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer.

Clinical significance

Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency.^[6] The enzyme ITPase dephosphorylates ribavirin triphosphate in vitro to ribavirin monophosphate, and reduced ITPase activity in 30% of humans potentiates mutagenesis in hepatitis C virus.^[10] Gene variants predicting reduced predicted ITPase activity have been associated with decreased risk of ribavirin-induced anemia, increased risk of thrombocytopenia, lower ribavirin concentrations, as well as a ribavirin-like reduced relapse risk following interferon-based therapy for hepatitis C virus (HCV) genotype 2 or 3 infection. ^[11]

Reading

• Holmes SL, Turner BM, Hirschhorn K (1979). "Human inosine triphosphatase: catalytic properties and population studies". Clin. Chim. Acta. 97 (2–3): 143–53. doi:10.1016/0009-8981(79)90410-8. PMID 487601.
• Fraser JH, Meyers H, Henderson JF, Brox LW, McCoy EE (1976). "Individual variation in inosine triphosphate accumulation in human erythrocytes". Clin. Biochem. 8 (6): 353–64. doi:10.1016/S0009-9120(75)93685-1. PMID 1204209.
• Clawson GA, Song YL, Schwartz AM, Shukla RR, Patel SG, Connor L, et al. (1992). "Interaction of human immunodeficiency virus type I Rev protein with nuclear scaffold nucleoside triphosphatase activity". Cell Growth Differ. 2 (11): 575–82. PMID 1667585.
• Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. Bibcode:2001Natur.414..865D. doi:10.1038/414865a. PMID 11780052.
• Sumi S, Marinaki AM, Arenas M, Fairbanks L, Shobowale-Bakre M, Rees D, et al. (2002). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency". Hum. Genet. 111 (4–5): 360–7. doi:10.1007/s00439-002-0798-z. PMID 12384777. S2CID 24240940.
• Cao H, Hegele RA (2003). "DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency". J. Hum. Genet. 47 (11): 620–2. doi:10.1007/s100380200095. PMID 12436200.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Marinaki AM, Duley JA, Arenas M, Ansari A, Sumi S, Lewis CM, et al. (2005). "Mutation in the ITPA gene predicts intolerance to azathioprine". Nucleosides Nucleotides Nucleic Acids. 23 (8–9): 1393–7. doi:10.1081/NCN-200027639. PMID 15571265. S2CID 86308163.
• Marinaki AM, Sumi S, Arenas M, Fairbanks L, Harihara S, Shimizu K, et al. (2005). "Allele frequency of inosine triphosphate pyrophosphatase gene polymorphisms in a Japanese population". Nucleosides Nucleotides Nucleic Acids. 23 (8–9): 1399–401. doi:10.1081/NCN-200027641. PMID 15571266. S2CID 36126159.
• Maeda T, Sumi S, Ueta A, Ohkubo Y, Ito T, Marinaki AM, et al. (2005). "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population". Mol. Genet. Metab. 85 (4): 271–9. doi:10.1016/j.ymgme.2005.03.011. PMID 15946879.
• Breen DP, Marinaki AM, Arenas M, Hayes PC (2005). "Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation". Liver Transpl. 11 (7): 826–33. doi:10.1002/lt.20377. PMID 15973722. S2CID 9301778.
• Porta J, Kolar C, Kozmin SG, Pavlov YI, Borgstahl GE (2006). "Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase". Acta Crystallographica Section F. 62 (Pt 11): 1076–81. doi:10.1107/S1744309106041790. PMC 2225220. PMID 17077483.
• Arenas M, Duley J, Sumi S, Sanderson J, Marinaki A (2007). "The ITPA c.94C>A and g.IVS2+21A>C sequence variants contribute to missplicing of the ITPA gene". Biochim. Biophys. Acta. 1772 (1): 96–102. doi:10.1016/j.bbadis.2006.10.006. PMID 17113761.
• Stenmark P, Kursula P, Flodin S, Graslund S, Landry R, Nordlund P, et al. (2007). "Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T". J. Biol. Chem. 282 (5): 3182–7. doi:10.1074/jbc.M609838200. PMID 17138556.
• Atanasova S, Shipkova M, Svinarov D, Mladenova A, Genova M, Wieland E, et al. (2007). "Analysis of ITPA phenotype-genotype correlation in the Bulgarian population revealed a novel gene variant in exon 6". Therapeutic Drug Monitoring. 29 (1): 6–10. doi:10.1097/FTD.0b013e3180308554. PMID 17304144. S2CID 7286658.