CACNA1D is a circadian gene and causes familial advanced sleep phase
成果类型：
Article
署名作者：
Webb, John M.; Abderemane-Ali, Fayal; Ashbrook, Liza; Ma, Mingyang; Nibber, Neha; Zou, Xianlin; Yamazaki, Maya; Wohler, Elizabeth; Sobreira, Nara; Minor Jr, Daniel L.; Fu, Ying - Hui; Ptacek, Louis J.
署名单位：
University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Johns Hopkins University; Johns Hopkins Medicine; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California San Francisco
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-13125
DOI：
10.1073/pnas.2424387122
发表日期：
2025-06-10
关键词：
channel beta-subunit
dependent inactivation
calcium
Mutation
identification
modulation
terminus
insights
variant
period
摘要：
Familial advanced sleep phase (FASP) is a heritable human sleep trait characterized by early sleep onset and offset times. We have identified five variants in five different families in the human voltage- gated calcium channel subunit alpha1 D (CACNA1D) that cosegregate with FASP. The variants in CACNA1D lead to altered channel dynamics in vitro. A mouse model of the E427K variant has a normal circadian period under constant darkness but displays altered phase shifts in response to light in the subjective night at circadian time (CT) 16 and CT22. Overall, these experiments establish CACNA1D as an FASP gene with altered entrainment, highlighting the ability of human genetics to uncover novel aspects of human circadian regulation.