{"gene":"SLC16A10","run_date":"2026-06-10T07:46:32","timeline":{"discoveries":[{"year":2006,"finding":"TAT1 (SLC16A10/MCT10) functions as a facilitated diffusion uniporter for aromatic amino acids with symmetrical selectivity and apparent affinity for influx and efflux, localizes to the basolateral membrane of small intestine enterocytes and kidney proximal tubule cells, and to the sinusoidal side of perivenous hepatocytes; it is not N-glycosylated.","method":"Xenopus oocyte transport assays, real-time RT-PCR, immunolocalization in mouse tissues","journal":"Journal of cellular physiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — transport assays in Xenopus oocytes combined with tissue localization; replicated across multiple experimental systems in one study","pmids":["16245314"],"is_preprint":false},{"year":2012,"finding":"TAT1 (SLC16A10) knockout mice show increased plasma, muscle, and kidney aromatic amino acid concentrations, aromatic aminoaciduria under high-protein diet, and impaired basolateral efflux of aromatic amino acids from small intestine enterocytes and proximal kidney tubule cells, establishing TAT1 as a required uniporter for equilibrating aromatic amino acid concentrations across specific epithelial membranes and enabling hepatocytes to act as a sink controlling extracellular aromatic amino acid concentrations.","method":"Knockout mouse phenotyping, plasma/tissue amino acid measurement, radiolabeled amino acid accumulation assays (in vivo injection, ex vivo everted gut sac), mRNA analysis of transporter expression","journal":"The Journal of physiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods in a clean knockout model; in vivo and ex vivo functional assays","pmids":["23045339"],"is_preprint":false},{"year":2013,"finding":"In Mct10/Mct8 double knockout mice, additional Mct10 inactivation partially rescues the elevated serum T3 and normalized serum T4 of Mct8 knockout mice, while worsening the hyperthyroid state in liver, kidneys, and thyroid gland, establishing that Mct10 contributes to thyroid hormone efflux from liver, kidneys, and thyroid gland, and participates in tissue-specific TH homeostasis.","method":"Mct10 knockout and Mct10/Mct8 double knockout mouse analysis; serum and tissue thyroid hormone measurement; hypothalamic TRH expression analysis","journal":"Endocrinology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic epistasis using single and double knockout mice with multiple tissue-level TH measurements","pmids":["24248460"],"is_preprint":false},{"year":2016,"finding":"MCT10 (and MCT8) facilitate T3 efflux from cells and potently stimulate T3 metabolism by type 3 deiodinase (D3), but do not augment steady-state nuclear T3 receptor activation, indicating that MCT10 bidirectional T3 transport predominantly affects T3 availability at the cell periphery (where D3 is located) rather than steady-state nuclear T3 levels.","method":"JEG3 cell transfection with TRβ1/luciferase T3-response element reporter, D3 metabolism assay, MCT10 and CRYM co-transfection experiments","journal":"Molecular and cellular endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional cell-based assays with multiple constructs, single lab","pmids":["27492966"],"is_preprint":false},{"year":2017,"finding":"Human MCT10 mediates facilitated diffusion of tryptophan independent of pH gradient when expressed in yeast; the N81K SNP completely abolishes tryptophan import without affecting MCT10 expression or plasma membrane localization, implicating N81 as a residue in the putative substrate trajectory.","method":"Yeast (S. cerevisiae) tat2Δ deletion complementation growth assay, tryptophan uptake, SNP mutagenesis, localization in HEK293T cells","journal":"Biochimica et biophysica acta. Biomembranes","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — functional reconstitution in yeast with mutagenesis and localization validation, single lab","pmids":["28754537"],"is_preprint":false},{"year":2011,"finding":"hMCT10 (and hMCT8) facilitate transport of the affinity-label N-bromoacetyl-[(125)I]T3 but are not themselves covalently modified (labeled) by it; differential inhibitory effects of iodothyronine derivatives with different side chains were observed on T3 transport by hMCT8 versus hMCT10, suggesting distinct substrate recognition.","method":"Radiolabeled BrAc-T3 transport and covalent labeling assays in transfected cells, iodothyronine derivative inhibition experiments","journal":"Molecular and cellular endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct transport and labeling assays, single lab, two orthogonal methods","pmids":["21315799"],"is_preprint":false},{"year":2018,"finding":"Mice deficient in both Slc16a2 (Mct8) and Slc16a10 (Mct10) exhibit hearing loss, retarded development of the cochlear sensory epithelium resembling hypothyroidism, progressive degeneration of cochlear hair cells, and loss of endocochlear potential; T3 administration largely restores sensory epithelium development and limited auditory function, demonstrating that both transporters are required for thyroid hormone delivery to cochlear tissues.","method":"Double knockout mouse auditory testing, cochlear histology, T3 rescue experiment","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic knockout with T3 rescue demonstrating TH-mediated mechanism","pmids":["29535325"],"is_preprint":false},{"year":2021,"finding":"In Mct10 knockout mouse thyrocytes, TSH receptor localization shifts from its canonical basolateral membrane location to vesicles; the additional absence of cathepsin K reverses this mislocalization back to basolateral, indicating that Mct10 contributes to TSH receptor homeostasis and canonical basolateral localization in thyrocytes.","method":"Immunofluorescence localization in single and multiple knockout mouse thyroid tissue (Mct10-/-, Ctsk-/-/Mct10-/-, Mct8-/y/Mct10-/-, Ctsk-/-/Mct8-/y/Mct10-/-)","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence in multiple genetic backgrounds, single lab","pmids":["34071318"],"is_preprint":false},{"year":2021,"finding":"The transcription factor Six1 directly binds a transcriptional enhancer of the Slc16a10 gene in skeletal muscle; Six1 loss-of-function reduces MCT10 expression, and MCT10 knockdown in tibialis anterior recapitulates the effect of Six1 on fast-twitch muscle gene expression and reduces thyroid hormone receptor-dependent reporter activity.","method":"Chromatin immunoprecipitation (genome-wide location analysis), in vivo RNA interference, RT-PCR, transcriptional reporter assay","journal":"Skeletal muscle","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP-validated direct binding plus in vivo RNAi functional phenotype, single lab","pmids":["34809717"],"is_preprint":false},{"year":2022,"finding":"Mct10 knockout male mice at 12 weeks have decreased trabecular femoral bone volume with reduced osteoblast numbers, while at 24 weeks they exhibit trabecular bone gain with increased osteoblast and decreased osteoclast numbers; in vitro osteoblast differentiation and activity are impaired by Mct10 deficiency, demonstrating a site- and age-dependent role for MCT10 in bone mass regulation.","method":"MicroCT skeletal analysis of Mct10 KO mice at multiple ages, osteoblast/osteoclast counting, in vitro osteoblast differentiation assays","journal":"Endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockout with multiple skeletal endpoints and in vitro validation, single lab","pmids":["34669927"],"is_preprint":false},{"year":2024,"finding":"SLC16A10 overexpression in MNT1 melanocytes increases melanin production, upregulates melanogenesis-related proteins TYR and TYRP1 (without changing their RNA levels), and increases intracellular phenylalanine uptake as shown by targeted metabolomics and ELISA; SLC16A10 knockdown reduces UVB-induced melanin production and phenylalanine uptake, establishing SLC16A10 as a transporter that promotes melanogenesis by facilitating phenylalanine import.","method":"SLC16A10 overexpression/knockdown in MNT1 cells, melanin quantification, Western blot, targeted metabolomics, ELISA, RT-PCR, UVB irradiation model","journal":"Experimental dermatology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional gain- and loss-of-function with multiple biochemical readouts, single lab","pmids":["39171634"],"is_preprint":false},{"year":2024,"finding":"miR-21-5p targets SLC16A10 in alveolar epithelial cells (A549); luciferase reporter assay confirmed direct targeting; SLC16A10 knockdown reduces LPS-induced IL-1β and TNF-α expression, while miR-21-5p inhibitor increases inflammatory cytokines and co-transfection of si-SLC16A10 rescues this effect, placing SLC16A10 downstream of miR-21-5p in the regulation of LPS-induced inflammatory response.","method":"Dual luciferase reporter assay, siRNA knockdown, miR-21-5p mimic/inhibitor transfection, RT-qPCR and Western blot for cytokines","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — luciferase reporter validates direct miR-21-5p targeting plus functional epistasis by rescue experiment, single lab","pmids":["38750066"],"is_preprint":false},{"year":2024,"finding":"Cryo-EM structures of ligand-free and thyroxine-bound human MCT10 in the inward-facing state were determined; structural analysis identified a network of conserved gate residues involved in conformational changes upon thyroxine binding that trigger ligand release on the opposite side of the membrane, revealing the alternating-access molecular mechanism of thyroid hormone transport.","method":"Cryo-EM structure determination of human MCT10 in inward-facing, thyroxine-bound state","journal":"bioRxiv","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with ligand-bound state and identification of functional gate residues; complemented by parallel MCT8 structural studies in same paper","pmids":[],"is_preprint":true}],"current_model":"SLC16A10 (MCT10/TAT1) is a facilitated diffusion uniporter that transports aromatic amino acids (phenylalanine, tyrosine, tryptophan) and thyroid hormones (T3, T4) bidirectionally across plasma membranes via an alternating-access mechanism involving conserved gate residues; it localizes to the basolateral membrane of intestinal, renal, and hepatic epithelia where it drives net aromatic amino acid efflux and thyroid hormone transport, contributes to tissue-specific thyroid hormone homeostasis in liver, kidney, thyroid, cochlea, bone, and skeletal muscle, maintains TSH receptor at its canonical basolateral location in thyrocytes, and promotes melanogenesis by facilitating phenylalanine uptake into melanocytes."},"narrative":{"mechanistic_narrative":"SLC16A10 (MCT10/TAT1) is a facilitated-diffusion uniporter that bidirectionally equilibrates aromatic amino acids (phenylalanine, tyrosine, tryptophan) across epithelial plasma membranes, where it localizes to the basolateral membrane of small-intestine enterocytes and kidney proximal-tubule cells and to the sinusoidal side of perivenous hepatocytes [PMID:16245314]. Genetic ablation in mice elevates plasma, muscle, and kidney aromatic amino acid levels and causes aromatic aminoaciduria under high-protein diet, establishing the transporter as required for net basolateral efflux from intestine and kidney and for hepatocyte-mediated control of extracellular aromatic amino acid concentrations [PMID:23045339]. The same carrier transports the thyroid hormones T3 and T4: it mediates hormone efflux from liver, kidney, and thyroid and participates in tissue-specific thyroid hormone homeostasis, acting in genetic epistasis with the related transporter MCT8 [PMID:24248460, PMID:21315799]. By facilitating T3 efflux, MCT10 chiefly governs peripheral T3 availability—potently feeding cell-surface type-3-deiodinase metabolism rather than steady-state nuclear receptor activation [PMID:27492966]. Cryo-EM of human MCT10 in inward-facing and thyroxine-bound states defines a conserved gate-residue network that drives an alternating-access mechanism for hormone translocation and release. Through these transport functions MCT10 supports thyroid-hormone delivery to the cochlea, where loss alongside MCT8 produces hypothyroid-like sensory-epithelium defects rescued by T3 [PMID:29535325], maintains canonical basolateral TSH-receptor localization in thyrocytes [PMID:34071318], regulates fast-twitch muscle gene programs as a direct Six1 target [PMID:34809717], modulates bone mass [PMID:34669927], and promotes melanogenesis by importing phenylalanine into melanocytes [PMID:39171634].","teleology":[{"year":2006,"claim":"Established the molecular identity and transport mode of TAT1, answering whether SLC16A10 is an active or facilitative carrier and where it acts in epithelia.","evidence":"Xenopus oocyte transport assays with symmetrical influx/efflux kinetics plus immunolocalization in mouse intestine, kidney, and liver","pmids":["16245314"],"confidence":"High","gaps":["Did not define physiological consequence of transport in vivo","Thyroid hormone handling not addressed"]},{"year":2011,"claim":"Demonstrated that MCT10 transports iodothyronines and recognizes substrates differently from MCT8, extending its substrate range beyond amino acids.","evidence":"Radiolabeled BrAc-T3 transport and covalent-labeling assays in transfected cells with iodothyronine derivative inhibition","pmids":["21315799"],"confidence":"Medium","gaps":["No structural basis for distinct substrate recognition","In vivo relevance of TH transport not yet tested"]},{"year":2012,"claim":"Showed that TAT1 is physiologically required for aromatic amino acid homeostasis, converting in vitro transport activity into an organismal function.","evidence":"Knockout mouse phenotyping with plasma/tissue amino acid measurement and ex vivo everted gut sac efflux assays","pmids":["23045339"],"confidence":"High","gaps":["Did not address thyroid hormone phenotypes","Mechanism of hepatocyte sink function not dissected at transporter level"]},{"year":2013,"claim":"Resolved the in vivo contribution of MCT10 to thyroid hormone efflux and its genetic interaction with MCT8 in tissue-specific TH homeostasis.","evidence":"Mct10 single and Mct10/Mct8 double knockout mice with serum and tissue TH measurements","pmids":["24248460"],"confidence":"High","gaps":["Tissue-level molecular mechanism of partial Mct8 rescue not defined","Did not separate amino acid from TH transport contributions"]},{"year":2016,"claim":"Clarified where MCT10-mediated T3 transport exerts its effect, distinguishing peripheral T3 availability from nuclear receptor activation.","evidence":"JEG3 cell TRβ1/luciferase reporter, D3 metabolism assays, and CRYM co-transfection","pmids":["27492966"],"confidence":"Medium","gaps":["Single cell-line model","Did not test endogenous tissue contexts"]},{"year":2017,"claim":"Mapped a residue in the substrate trajectory by showing a natural SNP abolishes transport, linking sequence variation to carrier function.","evidence":"Yeast tat2Δ complementation tryptophan-uptake assay with N81K mutagenesis and HEK293T localization control","pmids":["28754537"],"confidence":"Medium","gaps":["Physiological consequence of N81K in humans unknown","Single residue tested without full structural context"]},{"year":2018,"claim":"Demonstrated that MCT10 with MCT8 delivers thyroid hormone to cochlear tissue, explaining a sensory phenotype mechanistically through TH.","evidence":"Mct8/Mct10 double knockout auditory testing, cochlear histology, and T3 rescue","pmids":["29535325"],"confidence":"High","gaps":["Relative contribution of MCT10 versus MCT8 in cochlea not separated","Cell-type-specific transport site within cochlea undefined"]},{"year":2021,"claim":"Linked MCT10 to thyrocyte membrane organization, showing it maintains canonical basolateral TSH-receptor localization.","evidence":"Immunofluorescence localization across Mct10, Ctsk, and Mct8 compound knockout thyroid tissue","pmids":["34071318"],"confidence":"Medium","gaps":["Molecular mechanism connecting transport to TSHR trafficking unknown","Cathepsin K interaction mechanism not resolved"]},{"year":2021,"claim":"Identified an upstream transcriptional regulator and a muscle-specific role, placing Slc16a10 in a Six1-driven fast-twitch gene program.","evidence":"ChIP genome-wide location analysis, in vivo RNAi, and TH-dependent reporter assay in tibialis anterior","pmids":["34809717"],"confidence":"Medium","gaps":["Whether muscle effect is mediated by TH or amino acid transport not resolved","Single muscle model"]},{"year":2022,"claim":"Revealed a site- and age-dependent role for MCT10 in bone mass through effects on osteoblast differentiation.","evidence":"MicroCT of Mct10 KO mice at multiple ages with osteoblast/osteoclast counts and in vitro differentiation assays","pmids":["34669927"],"confidence":"Medium","gaps":["Transported substrate driving bone phenotype not identified","Mechanism for biphasic age-dependent effect unknown"]},{"year":2024,"claim":"Established a melanogenic function by showing SLC16A10 imports phenylalanine to drive melanin synthesis.","evidence":"Overexpression/knockdown in MNT1 melanocytes with melanin quantification, targeted metabolomics, ELISA, and UVB model","pmids":["39171634"],"confidence":"Medium","gaps":["How phenylalanine uptake increases TYR/TYRP1 protein without RNA change unclear","Single cell-line system"]},{"year":2024,"claim":"Placed SLC16A10 in an inflammatory regulatory circuit as a direct miR-21-5p target controlling LPS-induced cytokine output.","evidence":"Dual-luciferase reporter, siRNA knockdown, and miR-21-5p mimic/inhibitor rescue in A549 cells","pmids":["38750066"],"confidence":"Medium","gaps":["Transport mechanism linking SLC16A10 to cytokine induction undefined","Single epithelial cell line"]},{"year":2024,"claim":"Defined the structural basis of thyroid hormone transport, revealing the alternating-access gate mechanism.","evidence":"Cryo-EM of human MCT10 in inward-facing and thyroxine-bound states (preprint)","pmids":[],"confidence":"High","gaps":["Outward-facing state not captured","Aromatic amino acid bound structures not determined"]},{"year":null,"claim":"How the single transporter's distinct substrate streams (aromatic amino acids versus thyroid hormones) are integrated to produce its diverse tissue-specific phenotypes remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No human disease mutation has been linked to SLC16A10 via direct genetic evidence in this corpus","Substrate selectivity determinants between amino acids and iodothyronines not structurally separated","Regulatory partners coordinating transport with downstream phenotypes largely undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005215","term_label":"transporter activity","supporting_discovery_ids":[0,1,2,4,5,10,12]},{"term_id":"GO:0140104","term_label":"molecular carrier activity","supporting_discovery_ids":[0,3,5,12]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,4,7]}],"pathway":[{"term_id":"R-HSA-382551","term_label":"Transport of small molecules","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[1,3]}],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8TF71","full_name":"Monocarboxylate transporter 10","aliases":["Aromatic amino acid transporter 1","Solute carrier family 16 member 10","T-type amino acid transporter 1"],"length_aa":515,"mass_kda":55.5,"function":"Sodium- and proton-independent thyroid hormones and aromatic acids transporter (PubMed:11827462, PubMed:18337592, PubMed:28754537). Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels (PubMed:18337592). Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa) (PubMed:11827462, PubMed:28754537). Plays an important role in homeostasis of aromatic amino acids (By similarity)","subcellular_location":"Cell membrane; Basolateral cell membrane","url":"https://www.uniprot.org/uniprotkb/Q8TF71/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLC16A10","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000112394","cell_line_id":"CID001313","localizations":[{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"LAS1L","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID001313","total_profiled":1310},"omim":[{"mim_id":"607550","title":"SOLUTE CARRIER FAMILY 16 (MONOCARBOXYLIC ACID TRANSPORTER), MEMBER 10; SLC16A10","url":"https://www.omim.org/entry/607550"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Vesicles","reliability":"Supported"},{"location":"Cell Junctions","reliability":"Supported"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"choroid plexus","ntpm":24.8},{"tissue":"pancreas","ntpm":28.0},{"tissue":"skeletal muscle","ntpm":33.7}],"url":"https://www.proteinatlas.org/search/SLC16A10"},"hgnc":{"alias_symbol":["TAT1","MCT10"],"prev_symbol":[]},"alphafold":{"accession":"Q8TF71","domains":[{"cath_id":"1.20.1250.20","chopping":"65-254","consensus_level":"medium","plddt":94.1066,"start":65,"end":254},{"cath_id":"1.20.1250.20","chopping":"284-494","consensus_level":"medium","plddt":93.1581,"start":284,"end":494}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TF71","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TF71-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8TF71-F1-predicted_aligned_error_v6.png","plddt_mean":81.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLC16A10","jax_strain_url":"https://www.jax.org/strain/search?query=SLC16A10"},"sequence":{"accession":"Q8TF71","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8TF71.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8TF71/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8TF71"}},"corpus_meta":[{"pmid":"19541799","id":"PMC_19541799","title":"Molecular aspects of thyroid hormone transporters, including MCT8, MCT10, and OATPs, and the effects of genetic variation in these transporters.","date":"2009","source":"Journal of molecular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/19541799","citation_count":94,"is_preprint":false},{"pmid":"16245314","id":"PMC_16245314","title":"Basolateral aromatic amino acid transporter TAT1 (Slc16a10) functions as an efflux pathway.","date":"2006","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/16245314","citation_count":76,"is_preprint":false},{"pmid":"28785541","id":"PMC_28785541","title":"Hypothyroid Patients Encoding Combined MCT10 and DIO2 Gene Polymorphisms May Prefer L-T3 + L-T4 Combination Treatment - Data Using a Blind, Randomized, Clinical Study.","date":"2017","source":"European thyroid journal","url":"https://pubmed.ncbi.nlm.nih.gov/28785541","citation_count":71,"is_preprint":false},{"pmid":"24248460","id":"PMC_24248460","title":"Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency.","date":"2013","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/24248460","citation_count":71,"is_preprint":false},{"pmid":"23045339","id":"PMC_23045339","title":"T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control.","date":"2012","source":"The Journal of physiology","url":"https://pubmed.ncbi.nlm.nih.gov/23045339","citation_count":64,"is_preprint":false},{"pmid":"29535325","id":"PMC_29535325","title":"Deafness and loss of cochlear hair cells in the absence of thyroid hormone transporters Slc16a2 (Mct8) and Slc16a10 (Mct10).","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29535325","citation_count":40,"is_preprint":false},{"pmid":"24113777","id":"PMC_24113777","title":"Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8, Mct10, and organic anion-transporting polypeptides (Oatps) in a teleost fish.","date":"2013","source":"Comparative biochemistry and physiology. Part A, Molecular & integrative physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24113777","citation_count":39,"is_preprint":false},{"pmid":"27492966","id":"PMC_27492966","title":"Effects of thyroid hormone transporters MCT8 and MCT10 on nuclear activity of T3.","date":"2016","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/27492966","citation_count":22,"is_preprint":false},{"pmid":"28754537","id":"PMC_28754537","title":"Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the yeast Saccharomyces cerevisiae.","date":"2017","source":"Biochimica et biophysica acta. Biomembranes","url":"https://pubmed.ncbi.nlm.nih.gov/28754537","citation_count":16,"is_preprint":false},{"pmid":"21315799","id":"PMC_21315799","title":"The thyroid hormone transporters MCT8 and MCT10 transport the affinity-label N-bromoacetyl-[(125)I]T3 but are not modified by it.","date":"2011","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/21315799","citation_count":9,"is_preprint":false},{"pmid":"31280469","id":"PMC_31280469","title":"Variants in MCT10 protein do not affect FT3 levels in athyreotic patients.","date":"2019","source":"Endocrine","url":"https://pubmed.ncbi.nlm.nih.gov/31280469","citation_count":8,"is_preprint":false},{"pmid":"34669927","id":"PMC_34669927","title":"The Thyroid Hormone Transporter MCT10 Is a Novel Regulator of Trabecular Bone Mass and Bone Turnover in Male Mice.","date":"2022","source":"Endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/34669927","citation_count":8,"is_preprint":false},{"pmid":"39171634","id":"PMC_39171634","title":"The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine.","date":"2024","source":"Experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/39171634","citation_count":7,"is_preprint":false},{"pmid":"38750066","id":"PMC_38750066","title":"MiR-21-5p modulates LPS-induced acute injury in alveolar epithelial cells by targeting SLC16A10.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38750066","citation_count":7,"is_preprint":false},{"pmid":"34809717","id":"PMC_34809717","title":"Six1 promotes skeletal muscle thyroid hormone response through regulation of the MCT10 transporter.","date":"2021","source":"Skeletal muscle","url":"https://pubmed.ncbi.nlm.nih.gov/34809717","citation_count":6,"is_preprint":false},{"pmid":"37740545","id":"PMC_37740545","title":"Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank.","date":"2024","source":"The Journal of clinical endocrinology and metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/37740545","citation_count":4,"is_preprint":false},{"pmid":"40919667","id":"PMC_40919667","title":"Role of SLC16A10 in Psoriasis Through the Regulation of Arachidonic Acid Metabolism in Keratinocytes.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40919667","citation_count":3,"is_preprint":false},{"pmid":"33946552","id":"PMC_33946552","title":"Natural Autoimmunity to the Thyroid Hormone Monocarboxylate Transporters MCT8 and MCT10.","date":"2021","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/33946552","citation_count":1,"is_preprint":false},{"pmid":"34071318","id":"PMC_34071318","title":"The Amino Acid Transporter Mct10/Tat1 Is Important to Maintain the TSH Receptor at Its Canonical Basolateral Localization and Assures Regular Turnover of Thyroid Follicle Cells in Male Mice.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34071318","citation_count":1,"is_preprint":false},{"pmid":"41328587","id":"PMC_41328587","title":"Uncovering CD248, MMP28, and SLC16A10 in Sjögren's disease: a machine learning-driven SHAP approach for CD4+ T cell-associated biomarker discovery.","date":"2025","source":"Clinical and experimental rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/41328587","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.09.17.676751","title":"Placental transcriptome profiling in congenital Chagas disease: gene networks associated with transmission","date":"2025-09-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.17.676751","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.10.17.618737","title":"Molecular mechanism of thyroxine transport by monocarboxylate transporters","date":"2024-10-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.10.17.618737","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15307,"output_tokens":3429,"usd":0.048678,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11040,"output_tokens":3756,"usd":0.07455,"stage2_stop_reason":"end_turn"},"total_usd":0.123228,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"TAT1 (SLC16A10/MCT10) functions as a facilitated diffusion uniporter for aromatic amino acids with symmetrical selectivity and apparent affinity for influx and efflux, localizes to the basolateral membrane of small intestine enterocytes and kidney proximal tubule cells, and to the sinusoidal side of perivenous hepatocytes; it is not N-glycosylated.\",\n      \"method\": \"Xenopus oocyte transport assays, real-time RT-PCR, immunolocalization in mouse tissues\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — transport assays in Xenopus oocytes combined with tissue localization; replicated across multiple experimental systems in one study\",\n      \"pmids\": [\"16245314\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"TAT1 (SLC16A10) knockout mice show increased plasma, muscle, and kidney aromatic amino acid concentrations, aromatic aminoaciduria under high-protein diet, and impaired basolateral efflux of aromatic amino acids from small intestine enterocytes and proximal kidney tubule cells, establishing TAT1 as a required uniporter for equilibrating aromatic amino acid concentrations across specific epithelial membranes and enabling hepatocytes to act as a sink controlling extracellular aromatic amino acid concentrations.\",\n      \"method\": \"Knockout mouse phenotyping, plasma/tissue amino acid measurement, radiolabeled amino acid accumulation assays (in vivo injection, ex vivo everted gut sac), mRNA analysis of transporter expression\",\n      \"journal\": \"The Journal of physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods in a clean knockout model; in vivo and ex vivo functional assays\",\n      \"pmids\": [\"23045339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In Mct10/Mct8 double knockout mice, additional Mct10 inactivation partially rescues the elevated serum T3 and normalized serum T4 of Mct8 knockout mice, while worsening the hyperthyroid state in liver, kidneys, and thyroid gland, establishing that Mct10 contributes to thyroid hormone efflux from liver, kidneys, and thyroid gland, and participates in tissue-specific TH homeostasis.\",\n      \"method\": \"Mct10 knockout and Mct10/Mct8 double knockout mouse analysis; serum and tissue thyroid hormone measurement; hypothalamic TRH expression analysis\",\n      \"journal\": \"Endocrinology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic epistasis using single and double knockout mice with multiple tissue-level TH measurements\",\n      \"pmids\": [\"24248460\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MCT10 (and MCT8) facilitate T3 efflux from cells and potently stimulate T3 metabolism by type 3 deiodinase (D3), but do not augment steady-state nuclear T3 receptor activation, indicating that MCT10 bidirectional T3 transport predominantly affects T3 availability at the cell periphery (where D3 is located) rather than steady-state nuclear T3 levels.\",\n      \"method\": \"JEG3 cell transfection with TRβ1/luciferase T3-response element reporter, D3 metabolism assay, MCT10 and CRYM co-transfection experiments\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional cell-based assays with multiple constructs, single lab\",\n      \"pmids\": [\"27492966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Human MCT10 mediates facilitated diffusion of tryptophan independent of pH gradient when expressed in yeast; the N81K SNP completely abolishes tryptophan import without affecting MCT10 expression or plasma membrane localization, implicating N81 as a residue in the putative substrate trajectory.\",\n      \"method\": \"Yeast (S. cerevisiae) tat2Δ deletion complementation growth assay, tryptophan uptake, SNP mutagenesis, localization in HEK293T cells\",\n      \"journal\": \"Biochimica et biophysica acta. Biomembranes\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — functional reconstitution in yeast with mutagenesis and localization validation, single lab\",\n      \"pmids\": [\"28754537\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"hMCT10 (and hMCT8) facilitate transport of the affinity-label N-bromoacetyl-[(125)I]T3 but are not themselves covalently modified (labeled) by it; differential inhibitory effects of iodothyronine derivatives with different side chains were observed on T3 transport by hMCT8 versus hMCT10, suggesting distinct substrate recognition.\",\n      \"method\": \"Radiolabeled BrAc-T3 transport and covalent labeling assays in transfected cells, iodothyronine derivative inhibition experiments\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct transport and labeling assays, single lab, two orthogonal methods\",\n      \"pmids\": [\"21315799\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Mice deficient in both Slc16a2 (Mct8) and Slc16a10 (Mct10) exhibit hearing loss, retarded development of the cochlear sensory epithelium resembling hypothyroidism, progressive degeneration of cochlear hair cells, and loss of endocochlear potential; T3 administration largely restores sensory epithelium development and limited auditory function, demonstrating that both transporters are required for thyroid hormone delivery to cochlear tissues.\",\n      \"method\": \"Double knockout mouse auditory testing, cochlear histology, T3 rescue experiment\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic knockout with T3 rescue demonstrating TH-mediated mechanism\",\n      \"pmids\": [\"29535325\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In Mct10 knockout mouse thyrocytes, TSH receptor localization shifts from its canonical basolateral membrane location to vesicles; the additional absence of cathepsin K reverses this mislocalization back to basolateral, indicating that Mct10 contributes to TSH receptor homeostasis and canonical basolateral localization in thyrocytes.\",\n      \"method\": \"Immunofluorescence localization in single and multiple knockout mouse thyroid tissue (Mct10-/-, Ctsk-/-/Mct10-/-, Mct8-/y/Mct10-/-, Ctsk-/-/Mct8-/y/Mct10-/-)\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence in multiple genetic backgrounds, single lab\",\n      \"pmids\": [\"34071318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The transcription factor Six1 directly binds a transcriptional enhancer of the Slc16a10 gene in skeletal muscle; Six1 loss-of-function reduces MCT10 expression, and MCT10 knockdown in tibialis anterior recapitulates the effect of Six1 on fast-twitch muscle gene expression and reduces thyroid hormone receptor-dependent reporter activity.\",\n      \"method\": \"Chromatin immunoprecipitation (genome-wide location analysis), in vivo RNA interference, RT-PCR, transcriptional reporter assay\",\n      \"journal\": \"Skeletal muscle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-validated direct binding plus in vivo RNAi functional phenotype, single lab\",\n      \"pmids\": [\"34809717\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Mct10 knockout male mice at 12 weeks have decreased trabecular femoral bone volume with reduced osteoblast numbers, while at 24 weeks they exhibit trabecular bone gain with increased osteoblast and decreased osteoclast numbers; in vitro osteoblast differentiation and activity are impaired by Mct10 deficiency, demonstrating a site- and age-dependent role for MCT10 in bone mass regulation.\",\n      \"method\": \"MicroCT skeletal analysis of Mct10 KO mice at multiple ages, osteoblast/osteoclast counting, in vitro osteoblast differentiation assays\",\n      \"journal\": \"Endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with multiple skeletal endpoints and in vitro validation, single lab\",\n      \"pmids\": [\"34669927\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"SLC16A10 overexpression in MNT1 melanocytes increases melanin production, upregulates melanogenesis-related proteins TYR and TYRP1 (without changing their RNA levels), and increases intracellular phenylalanine uptake as shown by targeted metabolomics and ELISA; SLC16A10 knockdown reduces UVB-induced melanin production and phenylalanine uptake, establishing SLC16A10 as a transporter that promotes melanogenesis by facilitating phenylalanine import.\",\n      \"method\": \"SLC16A10 overexpression/knockdown in MNT1 cells, melanin quantification, Western blot, targeted metabolomics, ELISA, RT-PCR, UVB irradiation model\",\n      \"journal\": \"Experimental dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional gain- and loss-of-function with multiple biochemical readouts, single lab\",\n      \"pmids\": [\"39171634\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"miR-21-5p targets SLC16A10 in alveolar epithelial cells (A549); luciferase reporter assay confirmed direct targeting; SLC16A10 knockdown reduces LPS-induced IL-1β and TNF-α expression, while miR-21-5p inhibitor increases inflammatory cytokines and co-transfection of si-SLC16A10 rescues this effect, placing SLC16A10 downstream of miR-21-5p in the regulation of LPS-induced inflammatory response.\",\n      \"method\": \"Dual luciferase reporter assay, siRNA knockdown, miR-21-5p mimic/inhibitor transfection, RT-qPCR and Western blot for cytokines\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — luciferase reporter validates direct miR-21-5p targeting plus functional epistasis by rescue experiment, single lab\",\n      \"pmids\": [\"38750066\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structures of ligand-free and thyroxine-bound human MCT10 in the inward-facing state were determined; structural analysis identified a network of conserved gate residues involved in conformational changes upon thyroxine binding that trigger ligand release on the opposite side of the membrane, revealing the alternating-access molecular mechanism of thyroid hormone transport.\",\n      \"method\": \"Cryo-EM structure determination of human MCT10 in inward-facing, thyroxine-bound state\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with ligand-bound state and identification of functional gate residues; complemented by parallel MCT8 structural studies in same paper\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"SLC16A10 (MCT10/TAT1) is a facilitated diffusion uniporter that transports aromatic amino acids (phenylalanine, tyrosine, tryptophan) and thyroid hormones (T3, T4) bidirectionally across plasma membranes via an alternating-access mechanism involving conserved gate residues; it localizes to the basolateral membrane of intestinal, renal, and hepatic epithelia where it drives net aromatic amino acid efflux and thyroid hormone transport, contributes to tissue-specific thyroid hormone homeostasis in liver, kidney, thyroid, cochlea, bone, and skeletal muscle, maintains TSH receptor at its canonical basolateral location in thyrocytes, and promotes melanogenesis by facilitating phenylalanine uptake into melanocytes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLC16A10 (MCT10/TAT1) is a facilitated-diffusion uniporter that bidirectionally equilibrates aromatic amino acids (phenylalanine, tyrosine, tryptophan) across epithelial plasma membranes, where it localizes to the basolateral membrane of small-intestine enterocytes and kidney proximal-tubule cells and to the sinusoidal side of perivenous hepatocytes [#0]. Genetic ablation in mice elevates plasma, muscle, and kidney aromatic amino acid levels and causes aromatic aminoaciduria under high-protein diet, establishing the transporter as required for net basolateral efflux from intestine and kidney and for hepatocyte-mediated control of extracellular aromatic amino acid concentrations [#1]. The same carrier transports the thyroid hormones T3 and T4: it mediates hormone efflux from liver, kidney, and thyroid and participates in tissue-specific thyroid hormone homeostasis, acting in genetic epistasis with the related transporter MCT8 [#2, #5]. By facilitating T3 efflux, MCT10 chiefly governs peripheral T3 availability—potently feeding cell-surface type-3-deiodinase metabolism rather than steady-state nuclear receptor activation [#3]. Cryo-EM of human MCT10 in inward-facing and thyroxine-bound states defines a conserved gate-residue network that drives an alternating-access mechanism for hormone translocation and release [#12]. Through these transport functions MCT10 supports thyroid-hormone delivery to the cochlea, where loss alongside MCT8 produces hypothyroid-like sensory-epithelium defects rescued by T3 [#6], maintains canonical basolateral TSH-receptor localization in thyrocytes [#7], regulates fast-twitch muscle gene programs as a direct Six1 target [#8], modulates bone mass [#9], and promotes melanogenesis by importing phenylalanine into melanocytes [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established the molecular identity and transport mode of TAT1, answering whether SLC16A10 is an active or facilitative carrier and where it acts in epithelia.\",\n      \"evidence\": \"Xenopus oocyte transport assays with symmetrical influx/efflux kinetics plus immunolocalization in mouse intestine, kidney, and liver\",\n      \"pmids\": [\"16245314\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define physiological consequence of transport in vivo\", \"Thyroid hormone handling not addressed\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Demonstrated that MCT10 transports iodothyronines and recognizes substrates differently from MCT8, extending its substrate range beyond amino acids.\",\n      \"evidence\": \"Radiolabeled BrAc-T3 transport and covalent-labeling assays in transfected cells with iodothyronine derivative inhibition\",\n      \"pmids\": [\"21315799\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural basis for distinct substrate recognition\", \"In vivo relevance of TH transport not yet tested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed that TAT1 is physiologically required for aromatic amino acid homeostasis, converting in vitro transport activity into an organismal function.\",\n      \"evidence\": \"Knockout mouse phenotyping with plasma/tissue amino acid measurement and ex vivo everted gut sac efflux assays\",\n      \"pmids\": [\"23045339\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address thyroid hormone phenotypes\", \"Mechanism of hepatocyte sink function not dissected at transporter level\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Resolved the in vivo contribution of MCT10 to thyroid hormone efflux and its genetic interaction with MCT8 in tissue-specific TH homeostasis.\",\n      \"evidence\": \"Mct10 single and Mct10/Mct8 double knockout mice with serum and tissue TH measurements\",\n      \"pmids\": [\"24248460\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue-level molecular mechanism of partial Mct8 rescue not defined\", \"Did not separate amino acid from TH transport contributions\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Clarified where MCT10-mediated T3 transport exerts its effect, distinguishing peripheral T3 availability from nuclear receptor activation.\",\n      \"evidence\": \"JEG3 cell TRβ1/luciferase reporter, D3 metabolism assays, and CRYM co-transfection\",\n      \"pmids\": [\"27492966\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single cell-line model\", \"Did not test endogenous tissue contexts\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Mapped a residue in the substrate trajectory by showing a natural SNP abolishes transport, linking sequence variation to carrier function.\",\n      \"evidence\": \"Yeast tat2Δ complementation tryptophan-uptake assay with N81K mutagenesis and HEK293T localization control\",\n      \"pmids\": [\"28754537\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological consequence of N81K in humans unknown\", \"Single residue tested without full structural context\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated that MCT10 with MCT8 delivers thyroid hormone to cochlear tissue, explaining a sensory phenotype mechanistically through TH.\",\n      \"evidence\": \"Mct8/Mct10 double knockout auditory testing, cochlear histology, and T3 rescue\",\n      \"pmids\": [\"29535325\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contribution of MCT10 versus MCT8 in cochlea not separated\", \"Cell-type-specific transport site within cochlea undefined\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linked MCT10 to thyrocyte membrane organization, showing it maintains canonical basolateral TSH-receptor localization.\",\n      \"evidence\": \"Immunofluorescence localization across Mct10, Ctsk, and Mct8 compound knockout thyroid tissue\",\n      \"pmids\": [\"34071318\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism connecting transport to TSHR trafficking unknown\", \"Cathepsin K interaction mechanism not resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified an upstream transcriptional regulator and a muscle-specific role, placing Slc16a10 in a Six1-driven fast-twitch gene program.\",\n      \"evidence\": \"ChIP genome-wide location analysis, in vivo RNAi, and TH-dependent reporter assay in tibialis anterior\",\n      \"pmids\": [\"34809717\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether muscle effect is mediated by TH or amino acid transport not resolved\", \"Single muscle model\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Revealed a site- and age-dependent role for MCT10 in bone mass through effects on osteoblast differentiation.\",\n      \"evidence\": \"MicroCT of Mct10 KO mice at multiple ages with osteoblast/osteoclast counts and in vitro differentiation assays\",\n      \"pmids\": [\"34669927\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transported substrate driving bone phenotype not identified\", \"Mechanism for biphasic age-dependent effect unknown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established a melanogenic function by showing SLC16A10 imports phenylalanine to drive melanin synthesis.\",\n      \"evidence\": \"Overexpression/knockdown in MNT1 melanocytes with melanin quantification, targeted metabolomics, ELISA, and UVB model\",\n      \"pmids\": [\"39171634\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How phenylalanine uptake increases TYR/TYRP1 protein without RNA change unclear\", \"Single cell-line system\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placed SLC16A10 in an inflammatory regulatory circuit as a direct miR-21-5p target controlling LPS-induced cytokine output.\",\n      \"evidence\": \"Dual-luciferase reporter, siRNA knockdown, and miR-21-5p mimic/inhibitor rescue in A549 cells\",\n      \"pmids\": [\"38750066\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transport mechanism linking SLC16A10 to cytokine induction undefined\", \"Single epithelial cell line\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined the structural basis of thyroid hormone transport, revealing the alternating-access gate mechanism.\",\n      \"evidence\": \"Cryo-EM of human MCT10 in inward-facing and thyroxine-bound states (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Outward-facing state not captured\", \"Aromatic amino acid bound structures not determined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the single transporter's distinct substrate streams (aromatic amino acids versus thyroid hormones) are integrated to produce its diverse tissue-specific phenotypes remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No human disease mutation has been linked to SLC16A10 via direct genetic evidence in this corpus\", \"Substrate selectivity determinants between amino acids and iodothyronines not structurally separated\", \"Regulatory partners coordinating transport with downstream phenotypes largely undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005215\", \"supporting_discovery_ids\": [0, 1, 2, 4, 5, 10, 12]},\n      {\"term_id\": \"GO:0140104\", \"supporting_discovery_ids\": [0, 3, 5, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 4, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-382551\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":5,"faith_pct":80.0}}