Figure 3.

Schematic view of the physiological consequences and possible countermeasures against gain-of-function and loss-of-function mutations. In this example, the protein of interest (pink octogon) normally supports the assembly of a protein complex. (LEFT) In the wild-type situation, a complex is formed with other protein partners (blue polygons). (MIDDLE) A gain-of-function mutation results in the abnormal formation of protein polymers and protein aggregates, which may have constitutive activity or be toxic to the cell. Therapeutic options will consist in neutralizing the mutated protein and blocking the formation of aggregates with other proteins; pharmaceutical targets are already identified or may be identified readily in downstream pathways. (RIGHT) A loss-of-function mutation will result in the absence of the complex. The biological processes depending on the complex will be perturbed. Pharmaceutical targets are more evasive in the loss-of-function situation.