The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A (this protein) and BMPR1B and the type II receptor BMPR2. The ligands of these receptors are members of the TGF-β superfamily. TGF-βs and activins transduce their signals through the formation of heteromeric complexes with type I and type II receptors.
Mutations in BMPR1A are a cause of juvenile polyposis syndrome (JPS); also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core.
Genetic defects in BMPR1A are a cause of Cowden disease (CD), an autosomal dominant cancer syndrome characterized by multiple hamartomas and by a high risk for breast, thyroid and endometrial cancers.
Defects in BMPR1A are the cause of hereditary mixed polyposis syndrome 2 (HMPS2). Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas.
A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome. This syndrome shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome. The 10q23 microdeletion is also found in patients manifesting juvenile polyposis of infancy without cognitive disability. Juvenile polyposis of infancy is characterized by the appearance of extensive gastrointestinal juvenile hamartomatous polyposis in the first months of life.
Somatic mutations observed in BMPR1A are substitutions only. Most of them are located in the protein kinase domain. They are rare, occurring in a small minority of stomach, kidney and large intestine tumors.
References (open access):
Juvenile Polyposis Syndrome. Larsen Haidle J, Howe JR. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2003 May 13 [updated 2008 Sep 09].
A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Saetrom P, Biesinger J, Li SM, Smith D, Thomas LF, Majzoub K, Rivas GE, Alluin J, Rossi JJ, Krontiris TG, Weitzel J, Daly MB, Benson AB, Kirkwood JM, O'Dwyer PJ, Sutphen R, Stewart JA, Johnson D, Larson GP. Cancer Res. 2009 Sep 15;69(18):7459-65.