Genomic Insights into TASK-1 Reveal Functional Roles in Sleep Apnea

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Sleep apnea is a severe disorder that, if left untreated, can lead to serious long-term health issues and in some cases can be fatal. When a person has sleep apnea, their breathing repeatedly stops and starts during sleep. Despite being a common disease thought to affect many hundreds of millions of people worldwide, the causes of sleep apnea are still unknown. With their upcoming publication, Kavli INsD's Tucker Group identifies a key gene involved and potential therapeutic strategies while shedding light on some of the mysteries surrounding sleep apnea.

The KCNK3 gene in our bodies encodes TASK-1, a potassium (K+) ion channel involved in respiratory control, but the link between this gene and sleep apnea is not fully understood. In their study, the Tucker Group describes a new developmental disorder in children with associated sleep apnea which is called developmental delay with sleep apnea, or DDSA. This disorder is caused by rare new functional 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 including some drugs that are in clinical trials for the treatment of sleep apnea. These findings identify possible therapeutic strategies to help treat these children affected by this disorder, while also highlighting an important new role for TASK-1 K+ channels and their link with sleep apnea.

This study has recently been published in Nature Genetics and we are also delighted to reportthat an £880K MRC grant has been awarded to Kavli INsD investigators Stephen Tucker and Simon Newstead to continue their work on the molecular mechanisms underlying this disorder. Congratulations!

Since April 2021, Oxford University's KAVLI Institute for Nanoscience Discovery is proudly serving as a hub for research groups from seven different departments spanning both the medical and physical sciences, including Professor Stephen Tucker's Group from the Department of Physics.