THRA Gene - Thyroid Hormone Receptor Alpha | NCBI, UniProt, ClinVar

The THRA gene encodes thyroid hormone receptor alpha (TRα), a nuclear hormone receptor that binds triiodothyronine (T3) and regulates transcription of genes involved in development, metabolism, and cardiac function. Alternative splicing yields isoforms TRα1 and TRα2, with TRα2 lacking a functional ligand-binding domain. Mutations in THRA cause resistance to thyroid hormone alpha (RTHα), characterized by growth delay, constipation, and bradycardia. Somatic mutations and altered expression are implicated in several cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Thyroid hormone signaling pathway (KEGG hsa04919)

• Nuclear receptor transcription pathway (Reactome R-HSA-383280)

• Gene expression (transcription) (Reactome R-HSA-74160)

Thyroid hormone receptor alpha (TRα) is a 410-amino-acid nuclear receptor with an N-terminal domain, a DNA-binding domain containing two zinc fingers, a hinge region, and a C-terminal ligand-binding domain. It forms heterodimers with retinoid X receptors (RXRs) and binds to thyroid hormone response elements (TREs) in target gene promoters. Upon T3 binding, TRα undergoes a conformational change that releases corepressors and recruits coactivators, leading to transcriptional activation. TRα1 is the functional isoform; TRα2 lacks a ligand-binding domain and may act as a dominant-negative inhibitor. Post-translational modifications include phosphorylation and sumoylation, modulating its activity and stability.