MIM.603254 19p13.3 HGNC:11100
Wednesday 11 August 2004
The protein encoded by SMARCA4 is a member of the SWI/SNF family of proteins and is similar to the brahma protein of Drosophila.
Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes.
The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin.
In addition, this protein can bind BRCA1, as well as regulate the expression of the tumorigenic protein CD44. Multiple transcript variants encoding different isoforms have been found for this gene.
The SWI/SNF chromatin remodeling subunit BRG1 is a critical regulator of p53 necessary for proliferation of malignant cells. (#19448667#)
germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in rhabdoid tumor predisposition syndrome (#20137775#)
somatic mutation of SMARCA4 in :
- lung carcinoma (15%) (#15287030#)
- pancreatic carcinomas
- prostatic carcinomas
- mammary carcinomas (breast cancers)
BRG1/BRM expression was found lost in 10% of primary lung tumors correlating with a poor prognostic outcome.
Whereas Brg1-deficiency causes early embryonic lethality in mice, Brg1+/- animals are prone to epithelial tumors, possibly due to haploinsufficiency for Brg1 in tumor suppression, as the outgrowing tumors retained the remaining wild-type Brg1 allele. Brm-deficient mice are viable, likely via adaptive upregulation of Brg1.
Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Schneppenheim R, Frühwald MC, Gesk S, Hasselblatt M, Jeibmann A, Kordes U, Kreuz M, Leuschner I, Martin Subero JI, Obser T, Oyen F, Vater I, Siebert R. Am J Hum Genet. 2010 Feb 12;86(2):279-84. PMID: #20137775#