Journal article
Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.5MB, Terms of use)
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- Publisher copy:
- 10.1038/s41588-022-01185-x
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Genetics More from this journal
- Volume:
- 54
- Issue:
- 10
- Pages:
- 1534-1543
- Publication date:
- 2022-10-04
- Acceptance date:
- 2022-08-09
- DOI:
- EISSN:
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1546-1718
- ISSN:
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1061-4036
- Pmid:
-
36195757
- Language:
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English
- Keywords:
- Pubs id:
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1282109
- Local pid:
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pubs:1282109
- Deposit date:
-
2022-10-17
Terms of use
- Copyright holder:
- Sörmann et al.
- Copyright date:
- 2022
- Rights statement:
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Licence:
- CC Attribution (CC BY)
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