{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Abreo TJ"],"funding":["NICHD NIH HHS","NHLBI NIH HHS","NIMH NIH HHS","NINDS NIH HHS","NCI NIH HHS","NIH HHS","NIGMS NIH HHS"],"pubmed_abstract":["<i>KCNQ2</i> variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and <i>KCNQ2</i> G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 imm"],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.01.04.574177"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10802467"],"repository":["biostudies-literature"],"pubmed_title":["Plural molecular and cellular mechanisms of pore domain <i>KCNQ2</i> encephalopathy."],"pmcid":["PMC10802467"],"funding_grant_id":["R01 GM143380","U54 NS108874","R01 NS101596","K08 NS096029","P30 CA125123","K08 NS110924","U54 OD020351","R01 NS029709","S10 OD026804","R01 NS049119","R56 MH126953","P30 CA034196","P50 HD103555","R01 HL162842"],"pubmed_authors":["Springer K","Johnson J","Varghese N","Lutz C","Park KL","Tzingounis AV","Einsele-Scholz S","Maheshwari A","Soh H","Jankovic MJ","Vanoye CG","Sims S","Thompson EC","Habte B","Wang Z","Dudler L","Abreo TJ","Krishnan V","Cooper EC","Madabushi A","George AL","Noebels JL","Chavez AG","Zuberi AR","Ji Z"],"additional_accession":[]},"is_claimable":false,"name":"Plural molecular and cellular mechanisms of pore domain <i>KCNQ2</i> encephalopathy.","description":"<i>KCNQ2</i> variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and <i>KCNQ2</i> G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 imm","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2025-09-01T03:17:05.924Z","creation":"2025-09-01T03:08:14.61Z"},"accession":"S-EPMC10802467","cross_references":{"pubmed":["38260608"],"doi":["10.1101/2024.01.04.574177"]}}