TBL1Xencodes a WD40-repeat protein that is an essential subunit of the nuclear receptor corepressor (NCoR)-silencing mediator for retinoid and thyroid hormone receptors (SMRT) complex. This corepressor complex interacts with unliganded thyroid hormone receptors to modulate transcription of genes regulated by thyroid hormone and other nuclear receptors. Mutations identified in TBL1Xin central hypothyroidism patients are often missense or truncating variants localized in the highly conserved WD40 repeat domains, affecting protein stability and function in chromatin repression and corepressor complex assembly.
TBL1XmRNA is expressed in multiple tissues, including the pituitary and hypothalamus. Regarding the hearing abnormalities it was suggested that due to TBL1Xand subsequently NCoR-SMRT dysfunction there is differential expression of T3-regulated genes involved in ear development, such as pendrin. Similarly, the homologous gene TBL1Yis implicated in X-linked hearing loss.
TBL1X