{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Korchak EJ"],"funding":["Helen Gurley Brown Foundation and Jean Strouse Sharf and Lisa Sharf Green Cancer Research Fund","HHS | NIH | National Institute of General Medical Sciences","NINDS NIH HHS","HHS | NIH","HHS | NIH (NIH)","HHS | NIH | National Institute of General Medical Sciences (NIGMS)","NIGMS NIH HHS","Foundation for USP7-Related Disease"],"pagination":["e2510252122"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12501124"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["122(39)"],"pubmed_abstract":["Hao-Fountain syndrome is a rare neurodevelopmental disorder caused by mutations in the deubiquitinating enzyme Ubiquitin-Specific Protease 7 (USP7). Due to the novelty of the disease and its poorly understood molecular mechanisms, treatments for the syndrome are currently lacking. This study examines the effects of 11 patient-derived variants located within the catalytic domain of USP7, focusing on their impact on the enzyme's activity, thermodynamic stability, and substrate recognition. Our findings reveal a spectrum of functional consequences, ranging from complete inactivation to hyperactivation of USP7. Notably, we identify a specific subset of pathogenic variants whose catalytic activity can be significantly boosted using an allosteric activator, MS-8. These results provide insight in"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation."],"pmcid":["PMC12501124"],"funding_grant_id":["R35GM128864","N/A","R35 GM128864","R21 NS135343","R35GM156397","R35 GM156397","R21NS135343"],"pubmed_authors":["Khan H","Jaen Maisonet I","Korchak EJ","Schaaf CP","Bezsonova I","Salazar-Chaparro A","Caro P","Semenova IV","O'Neil AL","Buhrlage SJ","Sharafi M"],"additional_accession":[]},"is_claimable":false,"name":"Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation.","description":"Hao-Fountain syndrome is a rare neurodevelopmental disorder caused by mutations in the deubiquitinating enzyme Ubiquitin-Specific Protease 7 (USP7). Due to the novelty of the disease and its poorly understood molecular mechanisms, treatments for the syndrome are currently lacking. This study examines the effects of 11 patient-derived variants located within the catalytic domain of USP7, focusing on their impact on the enzyme's activity, thermodynamic stability, and substrate recognition. Our findings reveal a spectrum of functional consequences, ranging from complete inactivation to hyperactivation of USP7. Notably, we identify a specific subset of pathogenic variants whose catalytic activity can be significantly boosted using an allosteric activator, MS-8. These results provide insight in","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-15T14:33:31.147Z","creation":"2026-07-06T03:08:36.755Z"},"accession":"S-EPMC12501124","cross_references":{"pubmed":["40982686"],"doi":["10.1073/pnas.2510252122"]}}