SMARCB1 missense mutants destabilize SWI/SNF complex stability and remodeling activity
Study Design and Aims: This study utilizes a comprehensive deep mutational scanning (DMS) approach to systematically assess the functional consequences of 8,418 amino acid substitutions in the SMARCB1 gene, a core subunit of the SWI/SNF chromatin remodeling complex. The primary aim is to evaluate how missense mutations affect SMARCB1's tumor suppressor function and its role in the assembly and activity of distinct SWI/SNF subcomplexes (cBAF, PBAF, and GBAF). By addressing functional impacts across the entire coding sequence of SMARCB1, the study seeks to elucidate the molecular mechanisms underlying chromatin remodeling deficiencies caused by SMARCB1 missense mutations and their implications for cancer biology and diagnostics.Population Information: The study focuses on functional... (for more see dbGaP study page.)