SMARCA2

SMARCA2 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2), also known as BRM (Brahma homolog), is a catalytic subunit of the SWI/SNF chromatin-remodeling complex. This ATP-dependent chromatin remodeler regulates transcriptional activation/repression by altering nucleosome positioning. It functionally intersects with pathways including Wnt/β-catenin, p53, and RB/E2F, impacting cell differentiation, proliferation, and DNA repair. SMARCA2 aberrations are implicated in non-small cell lung cancer, gastric cancer, and Coffin-Siris syndrome. Though less frequently mutated than its paralog SMARCA4, SMARCA2 loss exhibits synthetic lethality with SMARCA4-deficient tumors, driving interest in SWI/SNF-targeted therapies. Current strategies explore ATPase inhibitors (e.g., BRM011) and epigenetic modulators to restore chromatin regulation, with preclinical models showing enhanced chemotherapy sensitivity upon SMARCA2 suppression.