TBL1XR1
Description
The TBL1XR1 (TBL1X/Y related 1) is a protein-coding gene located on chromosome 3.
TBL1XR1 is a protein encoded by the TBL1XR1 gene in humans. It is similar to members of the WD40 repeat-containing protein family, which are involved in regulation. WD40 repeats likely mediate protein-protein interactions, and these proteins play roles in various cellular processes, including signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly, and possibly cytotypic differentiation. Mutations in TBL1XR1 cause Pierpont syndrome, characterized by intellectual disability, distinctive facial features, and limb abnormalities. Mutations have also been found in lymphomas, including MYD88 wild-type Waldenstrom's macroglobulinemia. In prostate cancer, copy-number gains in TBL1XR1 are observed in around 15% of patients with localized disease, often alongside the megagene NAALADL2. These gains are associated with aggressive features of prostate cancer, such as high Gleason grade, advanced stage, positive surgical margins, and lymph node metastasis. The frequency of these gains increases in castrate-resistant and neuroendocrine prostate cancer. The region surrounding TBL1XR1 is rich in oncogenes.
TBL1XR1 is an F-box-like protein involved in recruiting the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. It plays a critical role in activating transcription by nuclear receptors. It is likely an integral part of the N-Cor corepressor complex, mediating the recruitment of the 19S proteasome complex. This leads to the degradation of the N-Cor complex through the proteasome, allowing for cofactor exchange and the initiation of transcription.
TBL1XR1 is also known as C21, DC42, IRA1, MRD41, TBLR1.
