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Monocarboxylate transporter 8
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<h2 id="function">Function</h2> <p>MCT8 actively transports a variety of iodo-<a href="/facts/Thyronine/4EqjtfRw">thyronines</a> including the thyroid hormones <a href="/facts/Triiodothyronine/MPBz6ApV">T3</a> and <a href="/facts/Thyroxine/9k4xJtCq">T4</a>.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p>A genetic disorder (discovered in 2003<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> and 2004<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a>) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in <a href="/facts/Hypotonia/73guQUlU">hypotonic</a>/floppy infants with delayed milestones). This genetic defect was known as <a href="/facts/Allan%25E2%2580%2593Herndon%25E2%2580%2593Dudley_syndrome/Kg3WVpd7">Allan–Herndon–Dudley syndrome</a> (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked <a href="/facts/Leukoencephalopathy/boCjmHuo">leukoencephalopathy</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> Some of the symptoms for this disorder as are follows: normal to slightly elevated <a href="/facts/Thyroid-stimulating_hormone/w8ettSpY">TSH</a>, elevated T3 and reduced T4 (ratio of T3/T4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to <a href="/facts/Pelizaeus%25E2%2580%2593Merzbacher_disease/dz9DyVBK">Pelizaeus–Merzbacher disease</a>, known as PMD<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a>), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating <a href="/facts/Lactic_acid/BsVRFx7s">lactate</a> level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. This disease can be ruled out with a simple TSH/T4/T3 thyroid test. </p> <h2 id="model-organisms">Model organisms</h2> <h3>Zebrafish</h3> <p>A knockout <a href="/facts/Zebrafish/Nxg1F1mG">zebrafish</a> line was generated in 2014 using the <a href="/facts/Zinc_finger_nuclease/f8LDUsT7">zinc-finger nuclease (ZFN)</a>-mediated targeted gene editing system.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> Similar to human patients, <i>the</i> zebrafish larvae exhibited neurological and behavioral deficiencies. They demonstrated reduced locomotor activity, altered <a href="/facts/Myelin/DKgJB8s8">myelin</a>-related genes and neuron-specific deficiencies in circuit formation.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h3><i>Xenopus</i></h3> <p>Expression of <i>mct8</i> has been characterised in <i><a href="/facts/Xenopus_laevis/khG1KPrd">Xenopus laevis</a></i><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> and <i><a href="/facts/Xenopus_tropicalis/uoS2ALeT">Xenopus tropicalis</a></i>.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Solute_carrier_family/Pnuz1TLA">Solute carrier family</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Halestrap AP, Meredith D (Feb 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". <i>Pflügers Archiv: European Journal of Physiology</i>. 447 (5): 619–628. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs00424-003-1067-2">10.1007/s00424-003-1067-2</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12739169">12739169</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:15498611">15498611</a>.</li> <li>Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ (Sep 2006). "Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8". <i>Nature Clinical Practice. Endocrinology & Metabolism</i>. 2 (9): 512–523. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fncpendmet0262">10.1038/ncpendmet0262</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16957765">16957765</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:25232696">25232696</a>.</li> <li>Grüters A (2007). "Thyroid hormone transporter defects". <i>Endocrine Development</i>. 10: 118–126. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1159%2F000106823">10.1159/000106823</a>. <a href="/facts/ISBN_(identifier)/15AdSPa9">ISBN</a> 978-3-8055-8296-4. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17684393">17684393</a>.</li> <li>Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". <i>Analytical Biochemistry</i>. 236 (1): 107–113. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fabio.1996.0138">10.1006/abio.1996.0138</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8619474">8619474</a>.</li> <li>Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (Apr 1997). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139146">"Large-scale concatenation cDNA sequencing"</a>. <i>Genome Research</i>. 7 (4): 353–358. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1101%2Fgr.7.4.353">10.1101/gr.7.4.353</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139146">139146</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9110174">9110174</a>.</li> <li>Price NT, Jackson VN, Halestrap AP (Jan 1998). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219047">"Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past"</a>. <i>The Biochemical Journal</i>. 329 (2): 321–328. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbj3290321">10.1042/bj3290321</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219047">1219047</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9425115">9425115</a>.</li> <li>Debrand E, Heard E, Avner P (Mar 1998). "Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene". <i>Genomics</i>. 48 (3): 296–303. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fgeno.1997.5173">10.1006/geno.1997.5173</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9545634">9545634</a>.</li> <li>Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (Jan 2004). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181904">"A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene"</a>. <i>American Journal of Human Genetics</i>. 74 (1): 168–175. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1086%2F380999">10.1086/380999</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181904">1181904</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/14661163">14661163</a>.</li> <li>Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, et al. (2004). "Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation". <i>Lancet</i>. 364 (9443). London, England: 1435–1437. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0140-6736%2804%2917226-7">10.1016/S0140-6736(04)17226-7</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15488219">15488219</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:37520843">37520843</a>.</li> <li>Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, et al. (Apr 2005). <a href="https://doi.org/10.1210%2Fen.2004-1179">"The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations"</a>. <i>Endocrinology</i>. 146 (4): 1701–1706. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fen.2004-1179">10.1210/en.2004-1179</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15661862">15661862</a>.</li> <li>Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S (Jun 2005). "X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene". <i>Journal of Neurology</i>. 252 (6): 663–666. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs00415-005-0713-3">10.1007/s00415-005-0713-3</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15834651">15834651</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:31994320">31994320</a>.</li> <li>Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH (Nov 2006). <a href="https://doi.org/10.1210%2Fme.2005-0256">"Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism"</a>. <i>Molecular Endocrinology</i>. 20 (11). Baltimore, Md.: 2761–2772. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fme.2005-0256">10.1210/me.2005-0256</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16887882">16887882</a>.</li> <li>Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (Nov 2006). <a href="https://doi.org/10.1016%2Fj.cell.2006.09.026">"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks"</a>. <i>Cell</i>. 127 (3): 635–648. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2Fj.cell.2006.09.026">10.1016/j.cell.2006.09.026</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17081983">17081983</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:7827573">7827573</a>.</li> <li>Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Grüters A, et al. (Jun 2007). <a href="https://doi.org/10.1210%2Fjc.2006-2570">"Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine"</a>. <i>The Journal of Clinical Endocrinology and Metabolism</i>. 92 (6): 2378–2381. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fjc.2006-2570">10.1210/jc.2006-2570</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17356046">17356046</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Lafrenière RG, Carrel L, Willard HF (Jul 1994). "A novel transmembrane transporter encoded by the XPCT gene in Xq13.2". Human Molecular Genetics. 3 (7): 1133–1139. doi:10.1093/hmg/3.7.1133. PMID 7981683. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (Oct 2003). "Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter". The Journal of Biological Chemistry. 278 (41): 40128–40135. doi:10.1074/jbc.M300909200. PMID 12871948. <a href="https://doi.org/10.1074%2Fjbc.M300909200" target="_blank">https://doi.org/10.1074%2Fjbc.M300909200</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, et al. (Jul 2005). "Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene". American Journal of Human Genetics. 77 (1): 41–53. doi:10.1086/431313. PMC 1226193. PMID 15889350. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226193" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226193</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (Oct 2003). "Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter". The Journal of Biological Chemistry. 278 (41): 40128–40135. doi:10.1074/jbc.M300909200. PMID 12871948. <a href="https://doi.org/10.1074%2Fjbc.M300909200" target="_blank">https://doi.org/10.1074%2Fjbc.M300909200</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (Oct 2003). "Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter". The Journal of Biological Chemistry. 278 (41): 40128–40135. doi:10.1074/jbc.M300909200. PMID 12871948. <a href="https://doi.org/10.1074%2Fjbc.M300909200" target="_blank">https://doi.org/10.1074%2Fjbc.M300909200</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (Jan 2004). "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". American Journal of Human Genetics. 74 (1): 168–175. doi:10.1086/380999. PMC 1181904. PMID 14661163. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181904" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181904</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, et al. (Sep 2011). "Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing". Journal of Medical Genetics. 48 (9): 606–609. doi:10.1136/jmg.2010.083535. PMID 21415082. S2CID 1157351. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Vaurs-Barrière C, Deville M, Sarret C, Giraud G, Des Portes V, Prats-Viñas JM, et al. (Jan 2009). "Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects". Annals of Neurology. 65 (1): 114–118. doi:10.1002/ana.21579. PMID 19194886. S2CID 27740314. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L (Sep 2014). "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLOS Genetics. 10 (9): e1004615. doi:10.1371/journal.pgen.1004615. PMC 4177677. PMID 25255244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177677" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177677</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L (Sep 2014). "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLOS Genetics. 10 (9): e1004615. doi:10.1371/journal.pgen.1004615. PMC 4177677. PMID 25255244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177677" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177677</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Mughal BB, Leemans M, Lima de Souza EC, le Mevel S, Spirhanzlova P, Visser TJ, et al. (2017-08-01). "Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1". Endocrinology. 158 (8): 2694–2705. doi:10.1210/en.2017-00108. ISSN 1945-7170. PMID 28591769. <a href="https://doi.org/10.1210%2Fen.2017-00108" target="_blank">https://doi.org/10.1210%2Fen.2017-00108</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Connors KA, Korte JJ, Anderson GW, Degitz SJ (2010-08-01). "Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis". General and Comparative Endocrinology. 168 (1): 149–159. doi:10.1016/j.ygcen.2010.04.015. ISSN 1095-6840. PMID 20417208. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> </ol>