Defective X-Gating of TASK-1 in a Novel Channelopathy Associated with Sleep Apnea - Sophion

Defective X-Gating of TASK-1 in a Novel Channelopathy Associated with Sleep Apnea


Author(s): Janina Sörmann, Marcus Schewe, Peter Proks, Thibault Jouen-Tachoire, Shanlin Rao, Karin E.J. Rödström, Thomas Müller, Thomas Baukrowitz, Matthew E. Hurles, Caroline F. Wright and Stephen J. Tucker


Clear link between DDSA mutations and Developmental Delay
with Sleep Apnea

DDSA mutations are gain-of-function even as ‘heterozygous’
channels

They have a higher open probability caused by a defective Xgating

They are less sensitive to GPCR mediation

DDSA mutations still retain sensitivity to inhibition by clinically
relevant drugs e.g. BAY1000493. Similar drug used in KOALA trial
(NCT04236440