Brahma-related gene 1 protein (BRG1)

Brahma-related gene 1 protein (BRG1, encoded by SMARCA4) is a highly conserved ATPase and core catalytic subunit of the SWI/SNF chromatin remodeling complex, which regulates transcription by altering chromatin structure. This protein is essential for the control of gene expression during development, especially in the brain and eye, and plays a role in the maintenance and differentiation of neural stem cells. Loss-of-function mutations or deficiencies are linked to neurodevelopmental disorders (such as Coffin-Siris syndrome and intellectual disabilities) and serve as a tumor suppressor in many human cancers. In the context of cancer, SMARCA4/BRG1 deficiency creates therapeutic vulnerabilities that are being exploited using synthetic lethality and epigenetic therapies. BRG1's core activities include transcriptional regulation, cell cycle control, and ensuring proper DNA accessibility for key developmental pathways.

Other names

SMARCA4BAF190ASWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4SWI/SNF ATPase

Most investigational therapeutics rely on synthetic lethality: targeting vulnerabilities in cancer cells arising from loss of BRG1 (e.g., SMARCA4-deficient tumors are sensitive to SMARCA2 inhibition or certain epigenetic modulators) Epigenetic modulation to restore gene expression profiles or compensate for BRG1 loss in chromatin remodeling