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SMARCA4 - Humpath.com - Human pathology

Home > A. Molecular pathology > SMARCA4


MIM.603254 19p13.3 HGNC:11100

Wednesday 11 August 2004

BRG1; "SNF2-like 4", "global transcription activator homologous sequence", "sucrose nonfermenting-like 4", "mitotic growth and transcription activator", "BRM/SWI2-related gene 1", "homeotic gene regulator", "nuclear protein GRB1", "brahma protein-like 1", "ATP-dependent helicase SMARCA4"; SNF2L4

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 :

- BRG1/BRM expression was found lost in 10% of primary lung tumors correlating with a poor prognostic outcome.

- SMARCA4-deficient digestive tumors

  • Undifferentiated gastrointestinal tract carcinomas are rare highly aggressive neoplasms with frequent but not obligatory rhabdoid features. Recent studies showed loss of SMARCB1 (INI1), a core subunit of the SWI/SNF chromatin remodeling complex, in 50% of tested cases. However, the molecular pathways underlying histologically similar but SMARCB1-intact cases are unknown.
  • Loss of different components of the SWI/SNF complex other than SMARCB1 can be observed in undifferentiated gastrointestinal carcinomas including novel SMARCA4-deficient and SMARCA2-deficient cases. It underlines the close link between SWI/SNF deficiency and the aggressive rhabdoid phenotype.
  • Frequent loss of SMARCA2 possibly points to fragility/vulnerability of the SWI/SNF complex as a consequence of lost core subunit SMARCB1. The exact molecular mechanisms underlying co-inactivation of different SWI/SNF subunits merit further investigations.
  • SWI/SNF Complex-deficient Undifferentiated/Rhabdoid Carcinomas of the Gastrointestinal Tract: A Series of 13 Cases Highlighting Mutually Exclusive Loss of SMARCA4 and SMARCA2 and Frequent Co-inactivation of SMARCB1 and SMARCA2. Agaimy A, Daum O, Märkl B, Lichtmannegger I, Michal M, Hartmann A. Am J Surg Pathol. 2015 Nov 5. PMID: 26551623

Animal models

- 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.

See also

- SWI/SNF complex
- chromatin modifier


- 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


  • Chromatin remodeling