TGFBR2 gene

The TGFBR2 gene encodes a receptor protein essential for regulating cell growth and tumor suppression, with mutations linked to aortic disorders and various cancers.

Normal Function

The TGFBR2 gene provides instructions for making a protein called transforming growth factor-beta (TGF-β) receptor type 2. 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 2 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 2, which turns on (activates) the receptor and allows it to bind to another receptor on the cell surface. These three proteins form a complex, which triggers signal transduction by activating other proteins in a signaling pathway called the TGF-β pathway.

Signals transmitted by the TGF-β receptor complex trigger various responses by the cell, including the growth and division (proliferation) of cells, the maturation of cells to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis). Because TGF-β receptor type 2 helps prevent cells from growing and dividing too rapidly or in an uncontrolled way, it can suppress the formation of tumors.

Health Conditions Related to Genetic Changes

Familial thoracic aortic aneurysm and dissection

At least nine TGFBR2 gene mutations have been identified in people with familial thoracic aortic aneurysm and dissection (familial TAAD). This disorder involves problems with the aorta, which can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm) or a sudden tearing of the layers in the aorta wall (aortic dissection). These mutations disturb signal transduction, which can impair cell growth and development.

Loeys-Dietz syndrome

More than 100 mutations in the TGFBR2 gene have been found to cause Loeys-Dietz syndrome type II. This condition affects connective tissue, leading to blood vessel abnormalities and skeletal deformities. Most mutations change single amino acids in TGF-β receptor type 2, resulting in a receptor with little or no function. Although the receptor has reduced function, TGF-β pathway signaling occurs at an even greater intensity than normal, likely due to a compensatory increase in the activity of other proteins in the pathway. This overactive signaling disrupts the development of connective tissue and various body systems.

Cancers

Some TGFBR2 gene mutations are acquired during a person's lifetime (somatic mutations) and are present only in certain cells. These mutations appear to increase the risk of developing various cancers by disrupting the signaling process that regulates cell division. It is estimated that 30 percent of malignant colon tumors have TGFBR2 gene mutations in their cells.