SMARCA4 (Transcription activator BRG1) is a SWI/SNF protein that activates and represses transcription. It is involved in chromatin remodeling and is required for activation of genes repressed by chromatin. It is involved in embryogenesis, spermatogenesis and tissue development, including proper smooth muscle formation and synapse development. It is also involved in oligodendrocyte differentiation. Loss of SMARCA4 results in developmental defects such as incomplete or dysfunctional gastrointestinal tracts, open ductus arteriosus of the heart, as well as severe neurological dysfunction. Furthermore, inherited mutations in SMARCA4 have been linked with Coffin-Siris Syndrome in humans, characterized by developmental delays and intellectual disability. In cancer, SMARCA4 is the most commonly mutated chromatin remodeling ATPase, with mutations found in a broad spectrum of tumors such as lung, adrenal and pancreatic cancers as well as medulloblastomas. In immunohistochemistry, SMARCA4 has nuclear positivity in all tissues throughout the body. References: Molecular and Cellular Biology. 31 (13): 2618–31, PMID: 21518954; Development. 139 (6): 1133–40, PMID: 22318225; Proceedings of the National Academy of Sciences of the United States of America. 109 (5): E252–9, PMID: 22233809. PLoS One. 8 (1): e55119, PMID: 23355908; Cold Spring Harbor Perspectives in Medicine. 6 (8): a026930, PMID: 27413115; Mol Cell Biol. 2016 Jan 1; 36(1): 70–83, PMID: 26459759; Cell. 2013 Jan 17;152(1-2):248-61, PMID: 23332759; Front. Mol. Neurosci. 2017. DOI: 10.3389/fnmol.2017.00243