{"id":6352,"date":"2023-02-17T07:13:19","date_gmt":"2023-02-17T07:13:19","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2019-spectrum-of-kv2-1-dysfunction-in-kcnb1%e2%80%90associated-neurodevelopmental-disorders\/"},"modified":"2023-02-17T07:13:19","modified_gmt":"2023-02-17T07:13:19","slug":"2019-spectrum-of-kv2-1-dysfunction-in-kcnb1%e2%80%90associated-neurodevelopmental-disorders","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2019-spectrum-of-kv2-1-dysfunction-in-kcnb1%e2%80%90associated-neurodevelopmental-disorders\/","title":{"rendered":"2019 &#8211; Spectrum of KV2.1 Dysfunction in KCNB1\u2010Associated Neurodevelopmental Disorders"},"content":{"rendered":"<p>Objective Pathogenic variants in\u00a0KCNB1, encoding the voltage\u2010gated potassium channel KV2.1, are associated with developmental and epileptic encephalopathy (DEE). Previous functional studies on a limited number of\u00a0KCNB1\u00a0variants indicated a range of molecular mechanisms by which variants affect channel function, including loss of voltage sensitivity, loss of ion selectivity, and reduced cell\u2010surface expression.Methods We evaluated a series of 17\u00a0KCNB1\u00a0variants associated with DEE or other neurodevelopmental disorders (NDDs) to rapidly ascertain channel dysfunction using high\u2010throughput functional assays. Specifically, we investigated the biophysical properties and cell\u2010surface expression of variant KV2.1 channels expressed in heterologous cells using high\u2010throughput automated electrophysiology and immunocytochemistry\u2013flow cytometry.Results Pathogenic variants exhibited diverse functional defects, including altered current density and shifts in the voltage dependence of activation and\/or inactivation, as homotetramers or when coexpressed with wild\u2010type KV2.1. Quantification of protein expression also identified variants with reduced total KV2.1 expression or deficient cell\u2010surface expression. Interpretation Our study establishes a platform for rapid screening of KV2.1 functional defects caused by\u00a0KCNB1\u00a0variants associated with DEE and other NDDs. This will aid in establishing\u00a0KCNB1\u00a0variant pathogenicity and the mechanism of dysfunction, which will enable targeted strategies for therapeutic intervention based on molecular phenotype.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[55],"target_categories":[61],"target_families":[333],"targets":[262],"resource_keyword":[],"class_list":["post-6352","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","therapeutic_areas-cns","target_categories-voltage-gated-ion-channels","target_families-kv-channels","targets-kv2-1"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6352","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6352"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6352"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6352"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6352"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6352"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6352"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6352"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6352"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6352"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}