• A rare genetic mutation in the SIK3 gene, named SIK3-N783Y, has been identified in people who naturally require only 4-6 hours of sleep.
• Mice engineered with the SIK3-N783Y mutation also exhibited reduced sleep duration, supporting the role of this gene in regulating sleep.
• The findings suggest that the SIK3 gene and its related pathways could be promising targets for developing new treatments for sleep disorders.

Researchers have discovered a rare genetic mutation, SIK3-N783Y, that enables certain individuals to function effectively on only four to six hours of sleep per night. This mutation affects the SIK3 gene, which plays a role in the sleep-wake cycle. Studies on both humans and mice have confirmed the impact of this mutation on sleep duration, opening potential new avenues for developing treatments for sleep disorders and enhancing sleep efficiency.

• What: Discovery of a rare genetic mutation, SIK3-N783Y, linked to natural short sleep (NSS).
• Who: Researchers from the Chinese Academy of Sciences and the University of California, San Francisco, led the study. The study involved human subjects with NSS and genetically modified mice.
• When: The findings were published in the journal PNAS on May 5, 2025.
• Where: The research was conducted in laboratories at the Chinese Academy of Sciences and the University of California, San Francisco.

The discovery of the SIK3-N783Y mutation provides valuable insights into the genetic mechanisms that regulate sleep duration. The fact that mice with the same mutation also exhibited reduced sleep further strengthens the link between the SIK3 gene and sleep. This research may lead to the development of targeted therapies for sleep disorders by focusing on the SIK3 pathway. Further research is needed to fully understand the long-term effects of this mutation and its potential interactions with other genes and environmental factors.

"Our bodies continue to work when we go to bed... These people [natural short sleepers], all these functions our bodies are doing while we are sleeping, they can just perform at a higher level than we can."

"These findings advance our understanding of the genetic underpinnings of sleep... further support for potential therapeutic strategies to enhance sleep efficiency"

The identification of the SIK3-N783Y genetic mutation marks a significant advancement in elucidating the complex genetic architecture of sleep, offering potential new avenues for research into sleep disorders and therapeutic interventions. The SIK3-N783Y mutation results in diminished kinase activity, altering protein phosphorylation profiles, especially at synaptic sites, and impacting sleep-wake cycles. Ongoing research will likely delve into the detailed mechanisms of the SIK3 gene and its broader kinase regulatory network, exploring its role in synaptic homeostasis and the modulation of sleep duration and quality. These investigations aim to uncover potential therapeutic targets for sleep-related disorders and to improve sleep efficiency. Furthermore, studies are focusing on specific conserved regions within SIK3 that could bidirectionally regulate its enzymatic activity, offering insights for future drug design and personalized sleep medicine approaches.