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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, contribute to genetic disease and comorbidities much more than non-allosteric proteins, and there is an association between being allosteric and involvement in disease; 2) they are enriched in many major disease types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes, or diseases of the central nervous system; 3) variants from cancer genome-wide association studies are enriched near allosteric proteins, indicating their importance to polygenic traits; and 4) the importance of allosteric proteins in disease is due, at least partly, to their central positions in protein-protein interaction networks, and less due to their dynamical properties.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009806","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T18:40:38Z","timestamp":1644432038000},"page":"e1009806","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Known allosteric proteins have central roles in genetic disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-1552","authenticated-orcid":true,"given":"Gy\u00f6rgy","family":"Abrus\u00e1n","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-2413","authenticated-orcid":true,"given":"David B.","family":"Ascher","sequence":"additional","affiliation":[]},{"given":"Michael","family":"Inouye","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"pcbi.1009806.ref001","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/prot.20232","article-title":"Is allostery an intrinsic property of all dynamic proteins?","volume":"57","author":"K Gunasekaran","year":"2004","journal-title":"Proteins Struct Funct Bioinforma."},{"key":"pcbi.1009806.ref002","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.sbi.2018.10.008","article-title":"On the perturbation nature of allostery: sites, mutations, and signal modulation","volume":"56","author":"E Guarnera","year":"2019","journal-title":"Curr Opin Struct Biol"},{"key":"pcbi.1009806.ref003","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1021\/acs.biochem.9b00486","article-title":"Inter-Active Site Communication Mediated by the Dimer 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