BMPR2

About BMPR2

BMPR2 on chromosome 2q33.1 encodes bone morphogenetic protein receptor type 2, a serine threonine kinase receptor of the TGF beta superfamily that is highly expressed in the endothelial cells and smooth muscle cells of the pulmonary arteries. BMP signaling normally restrains proliferation of these cells and maintains endothelial integrity. Germline BMPR2 variants, identified in 2000, are the most common genetic cause of pulmonary arterial hypertension, found in most families with heritable disease and in a smaller proportion of people with apparently idiopathic disease. Penetrance is incomplete and higher in women, and carriers tend to develop disease at a younger age with a more severe course. Pulmonary arterial hypertension involves remodeling and narrowing of small pulmonary arteries, causing raised pulmonary artery pressure, right heart strain, and right heart failure, and it presents with breathlessness on exertion, fatigue, chest pain, fainting, and swelling. Other genes involved include ACVRL1, ENG, SMAD9, CAV1, KCNK3, and TBX4. Treatments include endothelin receptor antagonists, PDE5 inhibitors, a soluble guanylate cyclase stimulator, prostacyclin pathway drugs, and sotatercept, an activin signaling inhibitor approved in 2024 that helps rebalance the pathway disrupted by BMPR2 deficiency. Genetic testing informs family counseling.