Exploration of the VUS 308 V>M in the BMP2 Human Gene

The BMP2 (Bone Morphogenetic Protein 2) is a human gene responsible for encoding a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily. The ligands, or the molecules that can bind to a receptor and send signaling within or between cells, of this family can bind to different TGF-beta receptors. The SMAD family then can become activated. The SMAD family are intracellular signal transducers that serve as a central facilitator for the TGF-beta superfamily and bone morphogenic proteins (BMP). Essentially, Smads acts as transcription factors and can have effect on osteoblast and osteoclast functions. As a result, this plays a significant role in the control of bone remodeling. Growth factor of the TGF-beta superfamily also contributes to other developmental processes including cardiogenesis, neurogenesis, and osteogenesis. Dysfunction of the BMP2 gene can lead to short stature, facial dysmorphism, skeletal abnormalities, cardiac defects, as well as Brachydactyly A2 (BDA2) which is a form of brachydactyly that is distinguished by shortening of the middle phalanges of the index finger and occasionally the fifth finger. I have chosen to examine and research the consequences of the BMP2 variant 308 V>M through the use of bioinformatic analysis and computationally modeling the protein with the variant to stimulate the predicted behavior in order to determine the significance of the variant. It is my goal that the results obtained can later be used to not only understand the gene in more depth, but also potentially provide geneticists and clinicians with information that may lead to more personalized pathways of medicine for those individuals who have the variant.