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.

中文翻译：

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CACNA1D 是一种昼夜节律基因，会导致家族性睡眠前期

家族性高级睡眠阶段 （FASP） 是一种可遗传的人类睡眠特征，其特征是睡眠开始和间隔时间早。我们已经在人电压门控钙通道亚基 alpha1 D （ CACNA1D ） 的五个不同家族中鉴定了与 FASP 共分离的五个变异。CACNA1D 中的变异导致体外通道动力学改变。E427K 变体的小鼠模型在持续黑暗下具有正常的昼夜节律，但在昼夜节律时间 （CT） 16 和 CT22 的主观夜间表现出响应光的变化相移。总体而言，这些实验将 CACNA1D 确定为夹带改变的 FASP 基因，突出了人类遗传学揭示人类昼夜节律调节新方面的能力。