Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea
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Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 1534-1543 |
Number of pages | 13 |
Journal | Nature genetics |
Volume | 54 (2022) |
Issue number | 10 |
Publication status | Published - 4 Oct 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 36195757 |
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