SMARCA4 gene

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

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.

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).

Genetics Home Reference provides information about lung cancer.

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.

Cytogenetic Location: 19p13.2, which is the short (p) arm of chromosome 19 at position 13.2

Molecular Location: base pairs 10,960,922 to 11,062,282 on chromosome 19 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)

Cytogenetic Location: 19p13.2, which is the short (p) arm of chromosome 19 at position 13.2
  • 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
  • SNF2
  • SNF2-beta
  • SNF2-like 4
  • SNF2L4
  • SNF2LB
  • sucrose nonfermenting-like 4
  • SWI2
  • transcription activator BRG1