Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

SMARCA4

Reviewed May 2013

What is the official name of the SMARCA4 gene?

The official name of this gene is “SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4.”

SMARCA4 is the gene's official symbol. The SMARCA4 gene is also known by other names, listed below.

What is the normal function of the SMARCA4 gene?

The SMARCA4 gene provides instructions for making a protein called BRG1, which forms one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed.

Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells. The BRG1 protein and other SWI/SNF subunits are thought to act as tumor suppressors, which keep cells from growing and dividing too rapidly or in an uncontrolled way.

The BRG1 protein uses a molecule called ATP, which provides energy for chromatin remodeling, although the exact mechanism of remodeling is unclear.

How are changes in the SMARCA4 gene related to health conditions?

Coffin-Siris syndrome - caused by mutations in the SMARCA4 gene

At least six mutations in the SMARCA4 gene can cause Coffin-Siris syndrome. This condition is characterized by delayed development, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features that are described as coarse. The SMARCA4 gene mutations involved in Coffin-Siris syndrome change single protein building blocks (amino acids) in or remove an amino acid from the BRG1 protein. Although it is unclear how these changes affect SWI/SNF complexes, researchers suggest that SMARCA4 gene mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cellular processes, which could explain the diverse signs and symptoms of Coffin-Siris syndrome. People with Coffin-Siris syndrome do not appear to have an increased risk of cancer (see below).

cancers - associated with the SMARCA4 gene

Mutations in the SMARCA4 gene have been found in certain types of cancer, particularly lung cancer. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. The mechanism by which mutations in the SMARCA4 gene contribute to lung cancer is unknown, although it is thought that changes in SWI/SNF complexes are involved. These changes may impair normal cell differentiation, which leads to the overgrowth of certain cell types, causing cancer. Alternatively, abnormal SWI/SNF complexes may disrupt the regulation of genes that help control the growth and division of cells, which leads to cancer. It is likely that other genetic changes in addition to SMARCA4 gene mutations are necessary for cancer development.

Where is the SMARCA4 gene located?

Cytogenetic Location: 19p13.2

Molecular Location on chromosome 19: base pairs 10,960,921 to 11,062,281

The SMARCA4 gene is located on the short (p) arm of chromosome 19 at position 13.2.

The SMARCA4 gene is located on the short (p) arm of chromosome 19 at position 13.2.

More precisely, the SMARCA4 gene is located from base pair 10,960,921 to base pair 11,062,281 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SMARCA4?

You and your healthcare professional may find the following resources about SMARCA4 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the SMARCA4 gene or gene products?

  • ATP-dependent helicase SMARCA4
  • BAF190
  • BAF190A
  • brahma protein-like 1
  • BRG1
  • BRG1-associated factor 190A
  • BRM/SWI2-related gene 1
  • FLJ39786
  • hSNF2b
  • MRD16
  • nuclear protein GRB1
  • protein brahma homolog 1
  • protein BRG-1
  • RTPS2
  • SMCA4_HUMAN
  • SNF2
  • SNF2-beta
  • SNF2L4
  • SNF2LB
  • SNF2-like 4
  • sucrose nonfermenting-like 4
  • SWI2
  • transcription activator BRG1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SMARCA4?

acids ; actin ; amino acid ; ATP ; cancer ; cell ; chromatin ; chromatin remodeling ; differentiation ; DNA ; gene ; gene expression ; helicase ; molecule ; protein ; subunit ; syndrome ; transcription ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/6597)
  • OMIM: SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY A, MEMBER 4 (http://omim.org/entry/603254)
  • Rodriguez-Nieto S, Cañada A, Pros E, Pinto AI, Torres-Lanzas J, Lopez-Rios F, Sanchez-Verde L, Pisano DG, Sanchez-Cespedes M. Massive parallel DNA pyrosequencing analysis of the tumor suppressor BRG1/SMARCA4 in lung primary tumors. Hum Mutat. 2011 Feb;32(2):E1999-2017. doi: 10.1002/humu.21415. Epub 2010 Dec 7. (http://www.ncbi.nlm.nih.gov/pubmed/21280140?dopt=Abstract)
  • Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012 Mar 18;44(4):376-8. doi: 10.1038/ng.2219. (http://www.ncbi.nlm.nih.gov/pubmed/22426308?dopt=Abstract)
  • Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011 Jun 9;11(7):481-92. doi: 10.1038/nrc3068. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21654818?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2013
Published: August 18, 2014