BMPR1A (Bone Morphogenetic Protein Receptor Type 1A / ALK3 Gene)
BMPR1A (bone morphogenetic protein receptor type 1A; HGNC:1076, NCBI Gene ID 657) is a human locus mapped to chromosome band 10q23.2 that encodes type I transmembrane serine/threonine kinase receptor BMPR1A / ALK3 (532 aa; EC 2.7.11.30). BMPR1A acts in BMP2/4/7-BMPR1A-SMAD1/5/8 anabolic signaling opposing Myostatin/Activin SMAD2/3 catabolism & intestinal stem-cell homeostasis, together with SMAD4 (Common-Mediator SMAD Gene), MSTN (Myostatin Gene), and ACVR2A (Activin Receptor Type-2A Gene). Encodes the ALK3 type I bone morphogenetic protein receptor that activates SMAD1/5/8 to promote osteogenesis, muscle hypertrophy, and intestinal crypt homeostasis.
Approved Symbol
BMPR1A
Chromosomal Locus
10q23.2
Encoded Product
Type I transmembrane serine/threonine kinase receptor BMPR1A / ALK3 (532 aa; EC 2.7.11.30)
Genomic Organization & Cytogenetic Locus: 13-exon gene (including two 5-prime non-coding exons) on chromosome 10q23.2 located immediately adjacent to PTEN, encoding a 532-amino-acid type I receptor with an extracellular cysteine-rich BMP-binding domain, an intracellular regulatory GS (glycine-serine) box, and a serine/threonine kinase catalytic domain.
Cellular & Tissue Expression Profile: Ubiquitously expressed across osteoblasts, chondrocytes, skeletal muscle fibers, cardiac myocytes, hair follicle stem cells, and intestinal crypt-villus mesenchyme and epithelium.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Upon binding bone morphogenetic proteins (BMP2, BMP4, BMP7, GDF5) in complex with type II receptors (BMPR2, ACVR2A, ACVR2B), phosphorylated BMPR1A activates receptor-regulated SMAD1, SMAD5, and SMAD8 (SMAD9), which compete directly with the catabolic Myostatin/Activin-SMAD2/3 pathway for the shared nuclear co-mediator SMAD4—thereby driving mTORC1 activation, repressing the E3 ubiquitin ligase MUSA1 (FBXO30), and promoting myofiber hypertrophy and osteoblast differentiation.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Heterozygous germline loss-of-function mutations in BMPR1A account for ~20–25% of autosomal dominant Juvenile Polyposis Syndrome (JPS, alongside SMAD4), where loss of BMP-mediated restraint of Wnt/beta-catenin signaling in intestinal crypt stem cells causes hamartomatous gastrointestinal polyps and elevated colorectal cancer risk; contiguous 10q23 microdeletions encompassing both BMPR1A and PTEN cause severe juvenile polyposis of infancy.
Therapeutic & Clinical Pharmacology: Enhancing BMP-BMPR1A-SMAD1/5/8 signaling (or freeing ACVR2A/2B from Myostatin/Activin so they can partner with BMPR1A) is a key mechanism by which follistatin and bimagrumab stimulate skeletal muscle anabolism and prevent denervation atrophy.