Relationship of a components position in the bone morphogenetic protein (BMP) pathway to human disease phenotypes. In general, there is a relationship between the position of a component in signaling pathway to the disease phenotype resulting from inactivation of that component. An example of this trend is the BMP pathway. Mutations in components acting at the start of the BMP signal transduction cascade such as a particular BMP ligand (e.g., Drosophila Dpp = Human BMP4/BMP2) or a specialized BMP type I receptor (DrosophilaSaxophone = type I receptor for the Screw and Glass Bottom Boat ligands) result in specific developmental defects (e.g., brachydactyly). Mutations acting on subsequent steps in the BMP pathway, which mediate the effects of several converging upstream inputs such as the universal type II BMP receptor (e.g.,Drosophila Punt = type II receptor mediating all BMP signaling) or the cytoplasmic/nuclear SMAD transducer (e.g.,Drosophila Medea = Human SMAD4) result in generalized misregulation of cellular growth control and cancer (e.g., colorectal or pancreatic cancer).
