{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGenome‐wide association studies have consistently implicated SLC16A9 in the regulation of serum uric acid levels and related metabolic traits. Variants in this gene are significantly associated not only with altered urate concentrations—as seen in large cohorts investigating hyperuricemia and gout—but also with changes in key metabolites, such as DL‐carnitine and propionyl‐L-carnitine. These findings, observed in diverse populations, indicate that SLC16A9 may influence urate metabolism and the risk of gout, potentially by impacting the balance between renal and intestinal excretion of urate. Moreover, intra-individual studies have shown that genetic variation in SLC16A9 contributes to the variability of serum uric acid levels over time."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExperimental investigations into the functional properties of SLC16A9, also referred to as hMCT9, have demonstrated that it acts as a transporter for creatine. Heterologous expression studies in Xenopus laevis oocytes revealed that hMCT9 exhibits both high- and low-affinity kinetic components and its activity is highly sensitive to extracellular pH and sodium levels. These studies further confirmed that hMCT9-mediated creatine uptake is modulated by proton gradients and can be selectively inhibited by specific substrates and analogs, underscoring its role in mediating the transport of creatine across cell membranes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTaken together, these converging lines of evidence support a multifaceted role for SLC16A9 in human metabolism. Its genetic associations with serum uric acid levels and gout, coupled with functional evidence of its role as a creatine transporter, point toward a key contribution in metabolic regulation. These insights not only enhance our understanding of the molecular basis underlying hyperuricemia and related metabolic disorders but also suggest that SLC16A9 may represent a novel target for therapeutic intervention in conditions such as gout and metabolic syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Melanie Kolz, Toby Johnson, Serena Sanna, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Common missense variant of monocarboxylate transporter 9 (MCT9/SLC16A9) gene is associated with renal overload gout, but not with all gout susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-013-0073-8"}], "href": "https://doi.org/10.1007/s13577-013-0073-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23990105"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23990105"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuya Futagi, Katsuya Narumi, Ayako Furugen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterization of the orphan transporter SLC16A9, an extracellular pH- and Na"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-sensitive creatine transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.11.137"}], "href": "https://doi.org/10.1016/j.bbrc.2019.11.137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31784090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31784090"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Atsushi Yamaguchi, Yuto Mukai, Tomoya Sakuma, et al. 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