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

Known allosteric proteins have central roles in genetic disease