{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:06:21Z","timestamp":1781103981360,"version":"3.54.1"},"reference-count":76,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"ANID | Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1240633"],"award-info":[{"award-number":["1240633"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"ANID | Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1220680"],"award-info":[{"award-number":["1220680"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","award":["NCN19_168"],"award-info":[{"award-number":["NCN19_168"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:p>\n                    Intrinsic neuronal excitability, defined by the balance between input and output signals, is crucial to neural function, and its disruption underlies various neurological diseases. Kv3.1 channels, encoded by\n                    <jats:italic toggle=\"yes\">KCNC1<\/jats:italic>\n                    , are essential for high-frequency action potential firing. Variants in these channels are associated with several subtypes of epilepsy. We report a patient with developmental regression and epilepsy, meeting Rett syndrome criteria, who carries a\n                    <jats:italic toggle=\"yes\">KCNC1<\/jats:italic>\n                    variant encoding the S474C substitution in Kv3.1 (Kv3.1\n                    <jats:sup>S474C<\/jats:sup>\n                    ). Electrophysiological and biochemical assays reveal that Kv3.1\n                    <jats:sup>S474C<\/jats:sup>\n                    reduces channel presence in the plasma membrane and is retained in the endoplasmic reticulum. In murine primary cortical neuron cultures expressing Kv3.1\n                    <jats:sup>S474C<\/jats:sup>\n                    , we observed reduced neuronal firing frequency and exclusion of the channel from the axon initial segment. Consistently, we found a decreased firing frequency using a conductance-based computational neuronal model. In summary, this study identifies a link between a\n                    <jats:italic toggle=\"yes\">KCNC1<\/jats:italic>\n                    variant and Rett syndrome, highlighting the importance of S474 residue in Kv3.1 channel trafficking and function in neurons.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2424514123","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:56:41Z","timestamp":1773334601000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <i>KCNC1<\/i>\n                    variant linked to Rett syndrome disrupts ER to Golgi trafficking of Kv3.1 channel"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-1986","authenticated-orcid":false,"given":"Diego","family":"Maureira","sequence":"first","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Rubilar","sequence":"additional","affiliation":[{"name":"Servicio de Neuropsiquiatr\u00eda Infantil, Hospital Cl\u00ednico San Borja Arriar\u00e1n","place":["Santiago, Chile"]},{"name":"Departamento de Pediatr\u00eda, Campus Centro, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5068-948X","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Santander","sequence":"additional","affiliation":[{"name":"Servicio de Neuropsiquiatr\u00eda Infantil, Hospital Cl\u00ednico San Borja Arriar\u00e1n","place":["Santiago, Chile"]},{"name":"Departamento de Pediatr\u00eda, Campus Centro, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-1366","authenticated-orcid":false,"given":"Hans","family":"Moldenhauer","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]},{"name":"Escuela de Tecnolog\u00eda M\u00e9dica, Universidad Santo Tom\u00e1s","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1878-4003","authenticated-orcid":false,"given":"Ian","family":"Silva","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]},{"name":"Centro de Oncolog\u00eda de Precisi\u00f3n, Universidad Mayor","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1389-2162","authenticated-orcid":false,"given":"Pablo","family":"Cruz","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-1037","authenticated-orcid":false,"given":"Denise","family":"Riquelme","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Qu\u00edmica y Biolog\u00eda, Universidad de Santiago de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Baeza","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]},{"name":"Centro de Bioinform\u00e1tica, Simulaci\u00f3n y Modelado, Facultad de Ingenier\u00eda, Universidad de Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7535-6883","authenticated-orcid":false,"given":"Wendy","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]},{"name":"Centro de Bioinform\u00e1tica, Simulaci\u00f3n y Modelado, Facultad de Ingenier\u00eda, Universidad de Talca","place":["Talca, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Orio","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Universidad de Valpara\u00edso","place":["Valpara\u00edso, Chile"]},{"name":"Centro Interdisciplinario de Neurociencia de Valpara\u00edso","place":["Valpara\u00edso, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1067-7106","authenticated-orcid":false,"given":"Evrim","family":"Servili","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2539-4929","authenticated-orcid":false,"given":"M\u00f3nica","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Servicio de Neuropsiquiatr\u00eda Infantil, Hospital Cl\u00ednico San Borja Arriar\u00e1n","place":["Santiago, Chile"]},{"name":"Departamento de Pediatr\u00eda, Campus Centro, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-5648","authenticated-orcid":false,"given":"El\u00edas","family":"Leiva-Salcedo","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda, Facultad de Qu\u00edmica y Biolog\u00eda, Universidad de Santiago de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-5722","authenticated-orcid":false,"given":"Oscar","family":"Cerda","sequence":"additional","affiliation":[{"name":"N\u00facleo Interdisciplinario de Biolog\u00eda y Gen\u00e9tica, Instituto de Ciencias Biom\u00e9dicas, Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]},{"name":"Millennium Nucleus of Ion Channel-Associated Diseases","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1317"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-08-02881.1998"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3144"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2016.0859"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24929"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17656"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50822"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50799"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-1885"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.03.013"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199810)37:1<69::AID-NEU6>3.0.CO;2-6"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2017"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/400_2007_032"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01892-0"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31537-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1105"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06045-0"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21517"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00803-9"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty897"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3675-07.2007"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(25)10594-4"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.74.1.207"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3932"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00006.2002"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.6.1505"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1928"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201806035"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00250"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.299305"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3565-10.2010"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2018.10.014"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.2511"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20163925"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000077"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51707"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00257.2021"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-024-00748-w"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104079"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105404"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac164"},{"key":"e_1_3_4_44_2","first-page":"2027","article-title":"Activation of conventional kinesin motors in clusters by Shaw voltage-gated K+ channels","volume":"126","author":"Barry J.","year":"2013","unstructured":"J. Barry , Activation of conventional kinesin motors in clusters by Shaw voltage-gated K+ channels. J. Cell Sci. 126, 2027\u20132041 (2013).","journal-title":"J. Cell Sci."},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2369"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018671108"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29594-w"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2023"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/35090026"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9712com"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.12.005"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21554"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-021-01040-1"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-61697-6"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19378"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013242"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.74"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6535"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00584"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.08.020"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173565"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.88.1.394"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09582"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.10.029"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113468"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00174.2016"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2220029120"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0839-18.2019"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.155"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23158"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu733"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01120-z"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900136R"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1570424"},{"key":"e_1_3_4_76_2","unstructured":"D. Maureira In A KCNC1 variant linked to rett syndrome disrupts ER to golgi trafficking of Kv3.1 channel (Version 1). Zenodo. https:\/\/doi.org\/10.5281\/zenodo.15162857. Deposited 27 February 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2424514123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:56:48Z","timestamp":1773334608000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2424514123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":76,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,3,17]]}},"alternative-id":["10.1073\/pnas.2424514123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2424514123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"assertion":[{"value":"2024-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2424514123"}}