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Comment
. 2022 Oct;54(10):1451-1452.
doi: 10.1038/s41588-022-01195-9.

Genomic insights into TASK-1 reveal functional roles in sleep apnea

Tatum S Simonson  1 , Esteban A Moya  1 , Atul Malhotra  2
Affiliations
Comment

Genomic insights into TASK-1 reveal functional roles in sleep apnea

Tatum S Simonson et al. Nat Genet. 2022 Oct.

Abstract

KCNK3 mutations identified in sleep apnea probands affect TASK-1 X-gate function. These changes lead to an increase in potassium current and open probability, as well as impaired sensitivity to G-protein-coupled receptor inhibitors.

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Conflict of interest statement

Competing interests

A.M. reports income related to medical education from Zoll, Livanova, Eli Lilly and Jazz. ResMed provided a philanthropic donation to University of California, San Diego. T.S.S. and E.A.M. declare no competing interests.

Figures

Fig. 1 |
Fig. 1 |. Mutations observed in sleep apnea probands show impaired TASK-1 channel function, as evaluated in X. oocytes.
Mutations in KCNK3 results in reduced open probability (PO) and deficient activation through GPCRs in TASK-1 channels, disrupting the proper functioning of the TASK-1 channel X-gate. BAY1000493 denotes a potent TASK-1 inhibitor compound. M1–M4, transmembrane helix units; Gαq, protein G alpha q subunit.
See this image and copyright information in PMC

Comment on

  • Gain-of-function mutations in KCNK3 cause a developmental disorder with sleep apnea.
    Sörmann 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, Rödström KEJ, Hahn MG, Müller T, Baukrowitz T, Hurles ME, Wright CF, Tucker SJ. Sörmann J, et al. Nat Genet. 2022 Oct;54(10):1534-1543. doi: 10.1038/s41588-022-01185-x. Epub 2022 Oct 4. Nat Genet. 2022. PMID: 36195757 Free PMC article.

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