  Allostery is a form of protein regulation, where ligands that bind sites
located apart from the active site can modify the activity of the protein. The
molecular mechanisms of allostery have been extensively studied, because
allosteric sites are less conserved than active sites, and drugs targeting them
are more specific than drugs binding the active sites. Here we quantify the
importance of allostery in genetic disease. We show that 1) known allosteric
proteins are central in disease networks, and contribute to genetic disease and
comorbidities much more than non-allosteric proteins, in many major disease
types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes,
or diseases of the central nervous system. 2) variants from cancer genome-wide
association studies are enriched near allosteric proteins, indicating their
importance to polygenic traits; and 3) the importance of allosteric proteins in
disease is due, at least partly, to their central positions in protein-protein
interaction networks, and probably not due to their dynamical properties.
