{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Arystarkhova E"],"funding":["Bigglesworth Family Foundation","NEI NIH HHS","Revance","Michael J. Fox Foundation","NINDS NIH HHS","NIH","Ipsen","NINDS"],"pagination":["104577"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7397496"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["132"],"pubmed_abstract":["Dominant mutations of ATP1A3, a neuronal Na,K-ATPase α subunit isoform, cause neurological disorders with an exceptionally wide range of severity. Several new mutations and their phenotypes are reported here (p.Asp366His, p.Asp742Tyr, p.Asp743His, p.Leu924Pro, and a VUS, p.Arg463Cys). Mutations associated with mild or severe phenotypes [rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), or early infantile epileptic encephalopathy (EIEE)] were expressed in HEK-293 cells. Paradoxically, the severity of human symptoms did not correlate with whether there was enough residual activity to support cell survival. We hypothesized that distinct cellular consequences may result not only from pump inactivation but also from protein misfolding. Biosynthesis was investig"],"journal":["Neurobiology of disease"],"pubmed_title":["Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition."],"pmcid":["PMC7397496"],"funding_grant_id":["P30 EY003790","U01 NS094148","NS058949","R01 NS058949","U01-NS094148"],"pubmed_authors":["Feschenko P","Salazar C","Sweadner KJ","Cook JF","Bressman SB","Brashear A","Demarest S","Luebbert T","Haq IU","Mochel F","Arystarkhova E","Saunders-Pullman R","Ozelius LJ"],"additional_accession":[]},"is_claimable":false,"name":"Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.","description":"Dominant mutations of ATP1A3, a neuronal Na,K-ATPase α subunit isoform, cause neurological disorders with an exceptionally wide range of severity. Several new mutations and their phenotypes are reported here (p.Asp366His, p.Asp742Tyr, p.Asp743His, p.Leu924Pro, and a VUS, p.Arg463Cys). Mutations associated with mild or severe phenotypes [rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), or early infantile epileptic encephalopathy (EIEE)] were expressed in HEK-293 cells. Paradoxically, the severity of human symptoms did not correlate with whether there was enough residual activity to support cell survival. We hypothesized that distinct cellular consequences may result not only from pump inactivation but also from protein misfolding. Biosynthesis was investig","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Dec","modification":"2026-05-03T22:17:06.352Z","creation":"2021-02-20T02:48:45Z"},"accession":"S-EPMC7397496","cross_references":{"pubmed":["31425744"],"doi":["10.1016/j.nbd.2019.104577"]}}