{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies using heterologous expression systems have established that SLC28A2, which encodes the human concentrative nucleoside transporter 2 (CNT2), is a high‐affinity, sodium‐dependent transporter that preferentially mediates the uptake of purine nucleosides and select deoxyribonucleosides. CNT2 exhibits efficient transport of endogenous substrates such as inosine and guanosine as well as nucleoside analog drugs (e.g., ribavirin), and its substrate selectivity has been elucidated in assays involving Xenopus oocytes and human-derived cell lines. The transporter’s kinetic properties and sodium-coupled uptake mechanism underscore its critical roles in intestinal absorption and hepatic disposition of both naturally occurring nucleosides and therapeutically administered analogs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic analyses of SLC28A2 have revealed that both coding and promoter region polymorphisms can modulate CNT2 expression and function. Functional studies in diverse populations have characterized several non‐synonymous variants that, while generally retaining the ability to transport nucleosides such as inosine and ribavirin, may alter the transport specificity for endogenous substrates. These findings suggest that genetic variability in SLC28A2 could contribute to interindividual differences in nucleoside homeostasis and influence patients’ responses to nucleoside analog therapeutics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical role in nucleoside salvage, CNT2 appears to interact with components of cellular energy metabolism, thereby linking nucleoside transport to broader metabolic regulation. Moreover, emerging associations between SLC28A2 polymorphisms and serum uric acid levels point to a potential involvement of CNT2 in modulating systemic metabolic traits and susceptibility to conditions such as hyperuricemia and gout. Collectively, these studies emphasize the clinical relevance of SLC28A2 in determining the pharmacokinetics and pharmacodynamics of nucleoside-derived drugs as well as its impact on endogenous metabolic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Karin M Gerstin, Mark J Dresser, Kathleen M Giacomini "}, {"type": "b", "children": [{"type": "t", "text": "Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00274.2001"}], "href": "https://doi.org/10.1152/ajprenal.00274.2001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12110519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12110519"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ho-Chul Shin, Christopher P Landowski, Duxin Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression and characterization of a sodium-dependent nucleoside transporter hCNT2 cloned from human duodenum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)01259-2"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "01259-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12893280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12893280"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryan P Owen, Jennifer H Gray, Travis R Taylor, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Cation coupling properties of human concentrative nucleoside transporters hCNT1, hCNT2 and hCNT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Membr Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09687860600942534"}], "href": "https://doi.org/10.1080/09687860600942534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17453413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17453413"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Taiki Yamamura, Katsuya Narumi, Tsukika Ohata, et al. 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