Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea
| dc.contributor.author | Vasudevan, Pradeep | |
| dc.date.accessioned | 2023-04-24T12:57:28Z | |
| dc.date.available | 2023-04-24T12:57:28Z | |
| dc.date.issued | 2022-10-04 | |
| dc.identifier.citation | Sörmann, J., Schewe, M., Proks, P., Jouen-Tachoire, T., Rao, S., Riel, E. B., Agre, K. E., Begtrup, A., Dean, J., Descartes, M., Fischer, J., Gardham, A., Lahner, C., Mark, P. R., Muppidi, S., Pichurin, P. N., Porrmann, J., Schallner, J., Smith, K., Straub, V., … Tucker, S. J. (2022). Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea. Nature genetics, 54(10), 1534–1543. https://doi.org/10.1038/s41588-022-01185-x | en_US |
| dc.identifier.other | 10.1038/s41588-022-01185-x | |
| dc.identifier.uri | http://hdl.handle.net/20.500.12904/16833 | |
| dc.description.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. | |
| dc.description.uri | https://www.nature.com/articles/s41588-022-01185-x | en_US |
| dc.language.iso | en | en_US |
| dc.title | Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea | en_US |
| dc.type | Article | en_US |
| rioxxterms.funder | Default funder | en_US |
| rioxxterms.identifier.project | Default project | en_US |
| rioxxterms.version | NA | en_US |
| rioxxterms.versionofrecord | https://doi.org/10.1038/s41588-022-01185-x | en_US |
| rioxxterms.type | Journal Article/Review | en_US |
| refterms.panel | Unspecified | en_US |
| html.description.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. | en_US |
| rioxxterms.funder.project | 94a427429a5bcfef7dd04c33360d80cd | en_US |