BMPR2

The BMPR2 gene provides instructions for making a protein called bone morphogenetic protein receptor, type II. The BMPR2 gene belongs to a family of genes originally identified for its role in regulating the growth and maturation (differentiation) of bone and cartilage. Recently, researchers have found that this gene family plays a broader role in regulating the growth and differentiation of numerous types of cells.

Bone morphogenetic protein receptor, type II spans the cell membrane, so that one end of the protein is on the outer surface of the cell and the other end remains inside the cell. This arrangement allows the protein to receive and transmit signals that help the cell respond to its environment by growing and dividing (cell proliferation) or by undergoing controlled cell death (apoptosis). This balance of cell proliferation and cell death regulates the number of cells in tissues.

pulmonary arterial hypertension - caused by mutations in the BMPR2 gene

Researchers have identified more than 140 BMPR2 mutations that cause pulmonary arterial hypertension. About half of these mutations disrupt the assembly of bone morphogenetic protein receptor, type II, reducing the amount of this protein in cells. Other mutations prevent bone morphogenetic protein receptor, type II from reaching the cell surface, or alter its structure so it cannot receive or transmit signals.

It remains unclear how BMPR2 mutations cause pulmonary arterial hypertension. Researchers suggest that a mutation in this gene promotes cell proliferation or prevents cell death, resulting in an overgrowth of cells in the smallest arteries throughout the lungs. As a result, these arteries narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, pressure increases in the pulmonary artery and in the heart chamber that pumps blood into the pulmonary artery (the right ventricle). Signs and symptoms of pulmonary arterial hypertension occur when increased pressure cannot fully overcome the elevated resistance and blood flow to the body is insufficient.