SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4 (commonly known as BRG1))

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4), commonly known as BRG1, is the ATPase core of the SWI/SNF chromatin remodeling complex. This protein plays a critical role in modifying chromatin structure to regulate the accessibility of DNA for transcription, replication, repair, and recombination. Possessing both ATPase and bromodomain motifs, SMARCA4 binds nucleosomes and reads epigenetic marks. It acts as a tumor suppressor and is frequently mutated or deleted in diverse cancers, including rhabdoid tumors, lung adenocarcinoma, and small cell carcinoma of the ovary. Germline or somatic alterations in SMARCA4 disrupt normal cell differentiation, cycles, and proliferation, giving rise to developmental syndromes and predisposing to aggressive tumors. Current therapeutic interest focuses on exploiting vulnerabilities in SMARCA4-mutant cancers, using epigenetic/kinase inhibitors or immunomodulatory approaches, since direct reactivation of SMARCA4 function is not yet feasible

Other names

BRG1Brahma-related gene 1ATP-dependent helicase SMARCA4BAF190Brahma protein-like 1BRG1-associated factor 190ABRM/SWI2-related gene 1Protein BRG-1RTPS2SNF2SWI2Transcription activator BRG1

Modulation of chromatin remodeling to restore transcriptional regulation; Synthetic lethality induction (e.g., DNA damage repair inhibition with ATR inhibitors or platinum agents); Epigenetic modification inhibition (e.g., BET, EZH2, HDAC inhibitors); Immune activation (immune checkpoint blockade)