Relationship between MCT8 gene and thyroid disorder

Thyroid hormone metabolism, intracellular activity, and transmembrane transport are processes facilitated by specific transport proteins. Over the past 20 years, several thyroid hormone transporters have been discovered, such as monocarboxylate transporter 8 (MCT8). MCT8 is a 12-domain transmembrane protein that crosses the cell membrane and transports monocarboxylates. The MCT8 gene (encoded by SLC16A2) is located on chromosome Xq13.2. This transporter (MCT8) is essential for the uptake of thyroid hormone (T3) in neurons and also plays a crucial role in optimal neuronal development. MCT8 supplies neurons with T3 and is found in the choroid plexus and neuronal cell membranes. The hypothalamus has been identified as an important site for integrating thyroid hormone feedback and gene control, and several pathogenic mutations in the MCT8 transporter are associated with it. These mutations include large-scale deletions involving one or more missing exons, frameshift mutations, deletions or insertions of a single amino acid, and alterations in a single amino acid. Some have also been observed in multiple unrelated cases. Several of these mutations have been functionally evaluated in cell lines that permanently or temporarily overexpress MCT8, resulting in complete loss of MCT8 function.