{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC16A12, also known as monocarboxylate transporter 12 (MCT12) or creatine transporter 2 (CRT2), is a key solute carrier expressed in the ocular lens, kidney, retina, and other tissues. Early genetic studies identified that mutations in SLC16A12, including a nonsense mutation and altered regulatory sequences in the 5′ untranslated region, are associated with congenital and juvenile cataracts, microcornea, and renal glucosuria—findings that support its critical role in the homeostasis of both lens and kidney cells. The tissue‐specific expression pattern, with high levels in the eye and kidney, highlights its importance for the maintenance of refractive properties of the lens and proper renal function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSubsequent functional studies have revealed that SLC16A12 mediates the transport of creatine via facilitative diffusion. Unlike the classic creatine transporter (SLC6A8), SLC16A12 appears to promote creatine efflux—its activity being influenced by mutations that alter conserved charged residues and by interactions with the molecular chaperone CD147. Investigations employing Xenopus oocyte expression systems and mammalian cell lines demonstrate that pathogenic variants result in reduced creatine uptake and mislocalization of the transporter, providing a mechanistic insight into how altered creatine handling might contribute to the development of cataract."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to creatine, recent evidence indicates that SLC16A12 contributes to the transport of guanidinoacetate, a creatine precursor, in renal proximal tubular epithelial cells. Studies employing primary cultures and siRNA-mediated knockdown in RPTECs demonstrate that SLC16A12 facilitates both the influx and efflux of guanidinoacetate, suggesting an essential role in releasing these metabolites into the circulation. This function adds another dimension to the role of SLC16A12 in renal substrate handling and metabolic homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Barbara Kloeckener-Gruissem, Kristof Vandekerckhove, Gudrun Nürnberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of solute carrier SLC16A12 associates with a syndrome combining juvenile cataract with microcornea and renal glucosuria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2007.12.013"}], "href": "https://doi.org/10.1016/j.ajhg.2007.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18304496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18304496"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jurian Zuercher, John Neidhardt, Istvan Magyar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alterations of the 5'untranslated region of SLC16A12 lead to age-related cataract."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.10-5193"}], "href": "https://doi.org/10.1167/iovs.10-5193"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20181839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20181839"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jeannette Abplanalp, Endre Laczko, Nancy J Philp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt175"}], "href": "https://doi.org/10.1093/hmg/ddt175"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23578822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23578822"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nasser Dhayat, Alexandre Simonin, Manuel Anderegg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause Glucosuria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2015040411"}], "href": "https://doi.org/10.1681/ASN.2015040411"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26376857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26376857"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masaki Takahashi, Hisanao Kishimoto, Yoshiyuki Shirasaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of monocarboxylate transporter 12 (SLC16A12/MCT12) as a facilitative creatine transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Pharmacokinet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dmpk.2020.01.008"}], "href": "https://doi.org/10.1016/j.dmpk.2020.01.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32249133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32249133"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andrina Stäubli, Nadejda Capatina, Yvonne Fuhrer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal creatine transport of mutations in monocarboxylate transporter 12 (MCT12) found in patients with age-related cataract can be partially rescued by exogenous chaperone CD147."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx310"}], "href": "https://doi.org/10.1093/hmg/ddx310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29088427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29088427"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ryuta Jomura, Yu Tanno, Shin-Ichi Akanuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Monocarboxylate transporter 12 as a guanidinoacetate efflux transporter in renal proximal tubular epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Biomembr (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamem.2020.183434"}], "href": "https://doi.org/10.1016/j.bbamem.2020.183434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32781157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32781157"}]}]}]}