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Lookup NU author(s): Professor Volker StraubORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s).Sleep apnea is a common disorder that represents a global public health burden. KCNK3 encodes TASK-1, a K+ channel implicated in the control of breathing, but its link with sleep apnea remains poorly understood. Here we describe a new developmental disorder with associated sleep apnea (developmental delay with sleep apnea, or DDSA) caused by rare de novo gain-of-function mutations in KCNK3. The mutations cluster around the ‘X-gate’, a gating motif that controls channel opening, and produce overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways. However, despite their defective X-gating, these mutant channels can still be inhibited by a range of known TASK channel inhibitors. These results not only highlight an important new role for TASK-1 K+ channels and their link with sleep apnea but also identify possible therapeutic strategies.
Author(s): Sormann J, Schewe M, Proks P, Jouen-Tachoire T, Rao S, Riel EB, Agre KE, Begtrup A, Dean J, Descartes M, Fischer J, Gardham A, Lahner C, Mark PR, Muppidi S, Pichurin PN, Porrmann J, Schallner J, Smith K, Straub V, Vasudevan P, Willaert R, Carpenter EP, Rodstrom KEJ, Hahn MG, Muller T, Baukrowitz T, Hurles ME, Wright CF, Tucker SJ
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2022
Volume: 54
Issue: 10
Pages: 1534-1543
Print publication date: 01/10/2022
Online publication date: 04/10/2022
Acceptance date: 09/08/2022
Date deposited: 28/06/2023
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Nature Research
URL: https://doi.org/10.1038/s41588-022-01185-x
DOI: 10.1038/s41588-022-01185-x
PubMed id: 36195757
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