AT-rich interactive domain-containing protein 1B (ARID1B)

AT-rich interactive domain-containing protein 1B (ARID1B) is a critical non-catalytic subunit of the SWI/SNF (BAF) chromatin-remodeling complex, which utilizes energy from ATP hydrolysis to reposition nucleosomes and modulate DNA accessibility. It plays a fundamental role in regulating gene expression programs essential for cell cycle progression, cellular differentiation, and particularly neurodevelopment (UniProt Q8NFD5). Germline mutations or deletions in ARID1B are the most frequent cause of Coffin-Siris syndrome, a condition characterized by intellectual disability and distinct physical features (Santen et al., 2012, PMID: 22426309). In the context of oncology, ARID1B has gained prominence as a major therapeutic vulnerability due to its synthetic lethal relationship with its paralog, ARID1A. In cancers where ARID1A is lost—a common occurrence in gynecological and gastrointestinal malignancies—tumor cells become absolutely dependent on ARID1B to maintain the functional integrity of the BAF complex (Helming et al., 2014, PMID: 25501368). Consequently, the development of ARID1B degraders, such as PROTACs, represents a promising precision medicine strategy to selectively target ARID1A-mutant tumors while minimizing impact on healthy cells.

Other names

BAF250B6q25.3DAN15ELD/OSA1OSA2P250RBRG1-associated factor 250b

Synthetic lethality (targeting ARID1B in ARID1A-deficient cells to disrupt BAF complex function)