TGFBR1

The TGFBR1 gene provides instructions for making a protein called transforming growth factor-beta (TGF-β) receptor type 1. This receptor transmits signals from the cell surface into the cell through a process called signal transduction. Through this type of signaling, the environment outside the cell affects activities inside the cell such as stimulation of cell growth and division.

To carry out its signaling function, the TGF-β receptor type 1 spans the cell membrane, so that one end of the protein projects from the outer surface of the cell (the extracellular domain) and the other end remains inside the cell (the intracellular domain). A protein called TGF-β attaches (binds) to the extracellular domain of the TGF-β receptor type 1, which turns on (activates) the receptor and allows it to bind to a similar receptor on the cell surface. The formation of this TGF-β receptor complex triggers signal transduction by activating other proteins in this signaling pathway.

Signals triggered through the TGF-β receptor complex prompt various responses by the cell. One such response is to inhibit cell growth and division. Based on this action, the TGF-β receptor type 1 is sometimes called a tumor suppressor. Tumor suppressors keep cells from growing and dividing too fast or in an uncontrolled way. TGF-β receptor signaling also helps control the process by which cells mature to carry out special functions (differentiation), and plays a role in the formation of the extracellular matrix, which is an intricate lattice that forms in the spaces between cells and provides structural support to tissues.

Loeys-Dietz syndrome - caused by mutations in the TGFBR1 gene

More than 30 mutations in the TGFBR1 gene have been found to cause Loeys-Dietz syndrome types I and II. Loeys-Dietz syndrome is a disorder that affects the connective tissue, which gives structure and support to blood vessels, the skeleton, and other parts of the body. Most of the TGFBR1 gene mutations that cause Loeys-Dietz syndrome change single protein building blocks (amino acids) in the TGF-β receptor type 1, resulting in a nonfunctional receptor protein. Although the receptor proteins are nonfunctional, cell signaling still occurs at an even greater frequency than normal, indicating that other, unknown mechanisms compensate for the lack of receptor activity. As a result, the signaling pathway is overactive, which disrupts development of connective tissue and various body systems and leads to the varied signs and symptoms of Loeys-Dietz syndrome types I and II.

Genetics Home Reference provides information about familial thoracic aortic aneurysm and dissection, which is also associated with changes in the TGFBR1 gene.