TGFB1 gene

transforming growth factor beta 1

The TGFB1 gene provides instructions for producing a protein called transforming growth factor beta-1 (TGFβ-1). The TGFβ-1 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). The TGFβ-1 protein is found throughout the body and plays a role in development before birth, the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGFβ-1 is particularly abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix). Within cells, this protein is turned off (inactive) until it receives a chemical signal to become active.

Approximately 10 mutations in the TGFB1 gene have been found to cause Camurati-Engelmann disease. Most of the mutations change one protein building block (amino acid) in the TGFβ-1 protein. The most common mutation replaces the amino acid arginine with the amino acid cysteine at position 218 in the TGFβ-1 protein (written as Arg218Cys or R218C).

All mutations that cause Camurati-Engelmann disease result in a TGFβ-1 protein that is always turned on (active). The overactive protein likely disrupts the regulation of bone growth and impairs muscle and body fat development. A disruption in the regulation of TGFβ-1 activity can lead to increased bone density and other features of Camurati-Engelmann disease.

Some TGFB1 gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes are called somatic mutations and are not inherited. Somatic mutations in the TGFB1 gene that cause alterations in the activity (expression) of the TGFβ-1 protein are associated with certain cancers. The altered protein expression may enhance several cancer-related events such as cell division (proliferation), cell motility, and the development of new blood vessels (angiogenesis) that nourish a growing tumor. The TGFβ-1 protein is abnormally active (overexpressed) in certain types of prostate cancers. Altered TGFβ-1 expression has also been found in breast, colon, lung, and bladder cancers.

A variation (polymorphism) in the TGFB1 gene that changes a single amino acid in the TGFβ-1 protein is associated with prostate cancer. In people with this polymorphism, the amino acid leucine is replaced with the amino acid proline at position 10 in the TGFβ-1 protein. Although it has no apparent effect in healthy people or those with a condition caused by a different mutation in the TGFB1 gene, this polymorphism is associated with accelerated disease progression and a poorer outcome in patients with prostate cancer.

Cytogenetic Location: 19q13.2, which is the long (q) arm of chromosome 19 at position 13.2

Molecular Location: base pairs 41,330,531 to 41,353,933 on chromosome 19 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)

Cytogenetic Location: 19q13.2, which is the long (q) arm of chromosome 19 at position 13.2
  • CED
  • diaphyseal dysplasia 1, progressive
  • DPD1
  • TGF-beta-1
  • TGF-beta 1 protein
  • TGFB
  • TGFbeta
  • transforming growth factor-beta 1
  • transforming growth factor, beta 1
  • transforming growth factor, beta 1 (Camurati-Engelmann disease)