{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:49:40Z","timestamp":1791856180746,"version":"4.3.4"},"reference-count":149,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009790","name":"University at Albany","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009790","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wires.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inosine triphosphate pyrophosphatase (ITPase), encoded by the <jats:italic>ITPA<\/jats:italic> gene in humans, is an important enzyme that preserves the integrity of cellular nucleotide pools by hydrolyzing the noncanonical purine nucleotides (deoxy)inosine and (deoxy)xanthosine triphosphate into monophosphates and pyrophosphate. Variants in the <jats:italic>ITPA<\/jats:italic> gene can cause partial or complete ITPase deficiency. Partial ITPase deficiency is benign but clinically relevant as it is linked to altered drug responses. Complete ITPase deficiency causes a severe multisystem disorder characterized by seizures and encephalopathy that is frequently associated with fatal infantile dilated cardiomyopathy. In the absence of ITPase activity, its substrate noncanonical nucleotides have the potential to accumulate and become aberrantly incorporated into DNA and RNA. Hence, the pathophysiology of ITPase deficiency could arise from metabolic imbalance, altered DNA or RNA regulation, or from a combination of these factors. Here, we review the known functions of ITPase and highlight recent work aimed at determining the molecular basis for <jats:italic>ITPA<\/jats:italic>\u2010associated pathogenesis which provides evidence for RNA dysfunction.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RNA in Disease and Development &gt; RNA in Development<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wrna.1790","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T09:48:04Z","timestamp":1682329684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inosine triphosphate pyrophosphatase: A guardian of the cellular nucleotide pool and potential mediator of <scp>RNA<\/scp> function"],"prefix":"10.1002","volume":"14","author":[{"given":"Jacob H.","family":"Schroader","sequence":"first","affiliation":[{"name":"The RNA Institute, University at Albany State University of New York  Albany New York USA"},{"name":"Department of Biological Sciences, University at Albany State University of New York  Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Handley","sequence":"additional","affiliation":[{"name":"Faculty of Biological Sciences University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1916-0261","authenticated-orcid":false,"given":"Kaalak","family":"Reddy","sequence":"additional","affiliation":[{"name":"The RNA Institute, University at Albany State University of New York  Albany New York USA"},{"name":"Department of Biological Sciences, University at Albany State University of New York  Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp1250"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0076-6879(78)51066-5"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(71)90261-9"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.07.005"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101378"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.33588\/rn.7105.2020239"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.10.006"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-111221-103208"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-021-00255-3"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.53"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.06.003"},{"key":"e_1_2_14_13_1","volume-title":"Biochemistry","author":"Berg J. 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