Figure 3

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