SMARCB1 gene

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1

The SMARCB1 gene provides instructions for making a protein that 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 SMARCB1 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 role of the SMARCB1 protein within the SWI/SNF complex is not fully understood.

At least five mutations in the SMARCB1 gene have been found to 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. These SMARCB1 gene mutations change or remove single protein building blocks (amino acids) in the SMARCB1 protein. Although it is unclear how these changes affect SWI/SNF complexes, researchers suggest that SMARCB1 gene mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cell activities, 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).

More than two dozen mutations in the SMARCB1 gene have been found in people with schwannomatosis, a disorder characterized by multiple noncancerous (benign) tumors called schwannomas that grow on nerves. This type of tumor arises from Schwann cells, which are specialized cells that normally form an insulating layer around the nerve.

SMARCB1 gene mutations associated with schwannomatosis lead to production of an altered SMARCB1 protein whose function is reduced but not eliminated. The altered protein is less able to control how cells grow and divide, which can allow tumors to develop. However, it is unknown why these mutations are predominantly associated with schwannomas, instead of other tumor types, in people with schwannomatosis.

It appears that mutations in SMARCB1 alone are not enough to trigger the development of schwannomas. Additional genetic changes (somatic mutations) that are acquired during a person's lifetime and are present only in certain cells may also be required for schwannomas to form.

Some people who have a mutation in the SMARCB1 gene never develop tumors, which is a situation known as reduced penetrance.

Mutations in the SMARCB1 gene cause rhabdoid tumor predisposition syndrome (RTPS). Individuals with this condition have an increased risk of developing aggressive cancerous growths called rhabdoid tumors, which form in the brain (where they are often called atypical teratoid/rhabdoid tumors) and in the kidney (where they are often called malignant rhabdoid tumors). These tumors usually occur in infants and young children. Some children with RTPS also develop schwannomas. RTPS is caused by a mutation in the SMARCB1 gene that is present in cells throughout the body (called a germline mutation). An additional somatic mutation that deletes the normal copy of the gene is needed for tumors to develop. In combination, the germline and somatic mutations lead to the absence of SMARCB1 protein.

Somatic mutations in both copies of the SMARCB1 gene, which result in the absence of SMARCB1 protein, cause noninherited (sporadic) rhabdoid tumors in children. The mechanism by which germline or somatic SMARCB1 gene mutations lead to rhabdoid tumors is unknown.

Cytogenetic Location: 22q11.23, which is the long (q) arm of chromosome 22 at position 11.23

Molecular Location: base pairs 23,786,931 to 23,834,518 on chromosome 22 (Homo sapiens Annotation Release 109, GRCh38.p12) (NCBI)

Cytogenetic Location: 22q11.23, which is the long (q) arm of chromosome 22 at position 11.23
  • BAF47
  • BRG1-associated factor 47
  • hSNF5
  • hSNFS
  • INI1
  • integrase interactor 1 protein
  • MRD15
  • PPP1R144
  • RDT
  • RTPS1
  • Sfh1p
  • SNF5
  • SNF5 homolog
  • SNF5L1
  • Snr1
  • sucrose nonfermenting, yeast, homolog-like 1
  • SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1