Summary
Recessive genetic diseases are more likely to be caused by protein destabilization than dominant genetic diseases (1).
Details
From (1), who carried out a site-saturation mutagenesis experiment on 500 human domains:
The contribution of stability to protein fitness also varies among genes with different modes of inheritance (Fig. 4e,f). In proteins mutated in recessive diseases, a median of 49% of variance in ESM1v predicted fitness is explained by changes in stability (Fig. 4e,f). This is consistent with many mutations in these proteins reducing function by destabilization during both evolution and in disease. In contrast, only 27% of variance in protein fitness is accounted for by stability changes in proteins mutated in dominant disorders, suggesting variants more frequently affect biophysical properties beyond stability. Changes in these additional properties may be the cause of dominance in human diseases.