Anomalous Behavior of Disease-Inflicting Polymorphic Variants of Nuclear Receptor THRβ of Indian Origin

Abstract

Thyroid hormone receptor β (THRβ) binds to thyroid hormones to execute various cellular and physiological processes as a ligand-inducible transcriptional factor. THRs, especially THRβ, are key players in the central regulation of the HPT axis. They ensure a delicate balance between thyroid hormone production and feedback control, allowing the body to adapt to changing environmental conditions. Polymorphisms in THRβ can lead to multiple clinical manifestations like resistance to thyroid hormone β, neurological or psychological disorders (like autism, intellectual disabilities, etc), and several types of cancers (papillary thyroid cancer, breast cancer, etc). This study examined two disease-inflicting polymorphic variants of THRβ, P323L, and P453S of Indian origin. It was observed that these variants exhibit impaired subcellular localization patterns, transcriptional functions, and compromised receptor stability. The study provides valuable insight into the cellular mechanism underlying receptor dysfunction and inflicting disease states. It is anticipated that disease-inflicting polymorphic variants of THRβ influence the structural and functional behavior of the receptor, contributing to the onset of disease. A concerted effort to gain the molecular basis of receptor dysregulation will help improve the assessment and management of THRβ-mediated diseases.