Human Transporters


MCT10 (Monocarboxylate transporter 10)

Aliases: TAT1, PRO0813

Gene name: Solute Carrier Family 16 Member 10 (SLC16A10)


Monocarboxylate transporter 10 is a member of the MCT family within the solute carrier transporter superfamily. Initially, MCT10/TAT1 was identified as a low-affinity ‘system T’ aromatic amino acid transporter with no thyroid hormone (TH) transport activity, but its high homology with MCT8, the most specific TH transporter, prompted subsequent experiments that revealed its affinity towards THs. MCT10, an integral membrane protein with 12 putative transmembrane domains, has a wide tissue distribution with highest expression in the kidney and skeletal muscle. To date, there are no known clinically significant polymorphisms of MCT10. 
The current guidelines from FDA and EMA do not contain recommendations on testing NCEs for in vitro inhibition of MCT10.


MCT10 It is ubiquitously expressed in human tissues, especially in the proximal tubules of the kidney and in skeletal muscle. Moderate or low levels are found in the placenta, small intestinal epithelium, heart, liver, spleen, erythrocytes and thymus[1-3]. In epithelial cells it is predominantly expressed in the basolateral membrane.

Function, physiology, and clinically significant polymorphisms

The SLC16A10 gene is located on chromosome 6q21-22 [1-3]. MCT10, like MCT8, contains 6 exons but has only one translation initiation site. MCT10 is a 515-amino-acid protein with 12 predicted transmembrane domains (TMD) [4-6]. Similar to MCT8, the N-and C- termini of MCT10 are located intracellularly; however, unlike all other MCT family members, it possesses an N-terminal PEST domain [1, 2]. MCT10 shares 49% amino acid identity with MCT8, with the highest homology in TMDs [7]. 
MCT10 is responsible for the Na+-independent, bidirectional, low affinity (KM between 0.5-3 mM) transport of the aromatic amino acids phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp), as well as of their derivatives such as L-3,4-dihydroxyphenylalanine (L-DOPA) [1] [8]. In addition, MCT10 transports 3,5,3’-triiodothyronine (T3) with high affinity (KM around 4 µM); the literature is divided on its ability to transport 3,5,3’,5’-tetraiodo-L-thyronine (T4) [8-10]. The TH degradation products 3-T1, 3’-T1, 3,3’-T2, 3,5-T2 and rT3 are probably also MCT10 substrates as they were found to inhibit T3 transport by 60-90%. The known MCT10 substrate L-Trp (1 mM) also inhibited T3 (1nM) transport by ~50% [11]. MCT8 and MCT10 transport T3 with similar affinities, but the capacity of MCT10-mediated T3 transport is higher [12]. 
Since MCT8 deficiency is known to cause severe neurological phenotypes [13], and MCT10 is a potent TH transporter, too, it is highly relevant to identify the effects of MCT10 mutations. Intriguingly, Mct10-knockout mice did not display any alterations in blood or tissue TH levels, nor any neurodegeneration. This is most likely explained by the overlapping substrate specificities and tissue distribution of MCT10 and MCT8 [14]. On the other hand, the plasma and urinary concentrations of Phe, Trp and Tyr were significantly elevated in Mct10-knockout mice. MCT10 plays a pivotal role in the homeostasis of aromatic amino acids and the amino acid recycling pathway in collaboration with the LAT2/4F2hc amino acid exchanger [15, 16].
So far, 22 missense variants have been reported in the SLC16A10 gene, but no association with TH-related abnormalities or diseases was observed. One study has found that the common single nucleotide polymorphism (SNP) rs14399 in the 3’UTR of MCT10 was associated with decreased serum TSH and increased T3 concentration in healthy Caucasian donors; this finding, however, remained unconfirmed in other studies where rs14399 was not related to abnormal serum TH levels [17, 18]. The human MCT10 variant N81K, when expressed in Saccharomyces cerevisiae, displayed Trp transport deficiency in spite of normal expression and localization of the protein [16].

Clinical significance

No reports of DDIs due to MCT10 inhibition have been posted to date. Hence, MCT10 is not regarded as a likely candidate for DDI liabilities. Although several SNPs have been identified, no clinical consequences of any MCT10 genetic variant have been found. The tricyclic antidepressant desipramine (Ki≈390 µM) and the phenolphthalein dye bromsulphthalein (BSP) (IC50≈250) were published as inhibitors of MCT10-mediated TH transport [19].

Regulatory requirements

The current guidelines from FDA and EMA do not contain recommendations on testing NCEs for in vitro inhibition of MCT10.


Endogenous substrates

In vitro substrates used experimentally

Substrate drugs


Skeletal muscle, bone, kidney, thyroid, liver, intestine, heart, erythrocytes, spleen

Aromatic amino acids (Phe, Tyr, Trp, L-DOPA), T3

T3, L-DOPA, Trp

None identified

BSP, desipramine



1.    Kim, D.K., et al., The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics, 2002. 79(1): p. 95-103.
2.    Kersseboom, S. and T.J. Visser, Tissue-specific effects of mutations in the thyroid hormone transporter MCT8. Arq Bras Endocrinol Metabol, 2011. 55(1): p. 1-5.
3.    Morris, M.E. and M.A. Felmlee, Overview of the proton-coupled MCT (SLC16A) family of transporters: characterization, function and role in the transport of the drug of abuse gamma-hydroxybutyric acid. AAPS J, 2008. 10(2): p. 311-21.
4.    Halestrap, A.P., The monocarboxylate transporter family--Structure and functional characterization. IUBMB Life, 2012. 64(1): p. 1-9.
5.    Halestrap, A.P. and D. Meredith, The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch, 2004. 447(5): p. 619-28.
6.    Kim, D.K., et al., Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem, 2001. 276(20): p. 17221-8.
7.    Friesema, E.C., et al., Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem, 2003. 278(41): p. 40128-35.
8.    Friesema, E.C., et al., Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol Endocrinol, 2008. 22(6): p. 1357-69.
9.    Thyroid Hormone, ed. A.N. K. 2012: In Tech Open Access Publisher. 125-156.
10.    Schweizer, U., et al., Structure and function of thyroid hormone plasma membrane transporters. Eur Thyroid J, 2014. 3(3): p. 143-53.
11.    Johannes, J., et al., Few Amino Acid Exchanges Expand the Substrate Spectrum of Monocarboxylate Transporter 10. Mol Endocrinol, 2016. 30(7): p. 796-808.
12.    Chan, S.Y., et al., The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation. J Physiol, 2011. 589(Pt 11): p. 2827-45.
13.    Jansen, J., Mutations in Thyroid Hormone Transporter MCT8: genotype, function and phenotype. 2008, Erasmus University Rotterdam.
14.    Muller, J., et al., Tissue-specific alterations in thyroid hormone homeostasis in combined Mct10 and Mct8 deficiency. Endocrinology, 2014. 155(1): p. 315-25.
15.    Mariotta, L., et al., T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control. J Physiol, 2012. 590(24): p. 6413-24.
16.    Uemura, S., et al., Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the yeast Saccharomyces cerevisiae. Biochim Biophys Acta Biomembr, 2017. 1859(10): p. 2076-2085.
17.    Roef, G.L., et al., Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones. Clin Chim Acta, 2013. 425: p. 227-32.
18.    van der Deure, W.M., R.P. Peeters, and T.J. Visser, Genetic variation in thyroid hormone transporters. Best Pract Res Clin Endocrinol Metab, 2007. 21(2): p. 339-50.
19.    Roth, S., A. Kinne, and U. Schweizer, The tricyclic antidepressant desipramine inhibits T3 import into primary neurons. Neurosci Lett, 2010. 478(1): p. 5-8.





Solvo Transporter Book 4th Edition
Transporter Book 4th edition
  • 63 transporters
  • over 1500 references
  • comprehensive information on holistic models and proteomics for transporter research
  • changes in the regulatory landscape and scientific insights

Get the Book