• A rare genetic mutation, SIK3-N783Y, has been identified in natural short sleepers (NSS) who thrive on approximately 4-6 hours of sleep.
• The mutation affects the SIK3 gene, hindering its ability to transfer phosphate molecules, impacting the sleep-wake cycle, potentially leading to more efficient sleep.
• Mice engineered with the SIK3-N783Y mutation also experienced reduced sleep duration, suggesting a conserved role of SIK3 in sleep regulation across species.

Scientists have identified a rare genetic mutation, named SIK3-N783Y, in individuals who are 'natural short sleepers' (NSS). These individuals can function optimally on approximately 4-6 hours of sleep per night, significantly less than the 7-9 hours recommended for most adults. The discovery provides insights into the genetic underpinnings of sleep regulation and could potentially lead to the development of new treatments for sleep disorders. The research involved studying a woman in her 70s with NSS and genetically modifying mice to carry the identified mutation.

• What: Discovery of a new genetic mutation (SIK3-N783Y) linked to natural short sleep (NSS). This mutation affects the SIK3 gene and impacts its role in the sleep-wake cycle.
• Who: Ying-Hui Fu (University of California, San Francisco), researchers from the Chinese Academy of Sciences, natural short sleepers, and laboratory mice.
• When: Findings published on May 5, 2025, in the journal PNAS. The research involved studies conducted recently.
• Where: Research conducted at the University of California, San Francisco and the Chinese Academy of Sciences. Studies involved human subjects and laboratory mice.

The discovery of the SIK3-N783Y mutation provides further evidence for the genetic basis of sleep duration. The mutation's impact on the SIK3 protein's ability to transfer phosphate molecules suggests a critical role for this process in regulating the sleep-wake cycle. The finding that mice with the mutation also experienced reduced sleep duration highlights the conserved nature of this genetic mechanism across species. This research opens new avenues for developing targeted therapies to improve sleep efficiency and address sleep disorders.

"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 mutation, one of now five identified genetic mutations related to sleep, provides critical insights into the genetic mechanisms regulating sleep duration and efficiency, highlighting the significant role of genetics in sleep health. This mutation, found in individuals who thrive on short sleep, diminishes SIK3 kinase activity, altering protein phosphorylation at synaptic sites and affecting multiple sleep-related kinase pathways. Studies in mice confirm that this mutation reduces sleep time and increases EEG delta power. These findings offer potential therapeutic strategies for enhancing sleep efficiency and treating sleep disorders, including the development of drugs targeting SIK3. Further research into the SIK3 regulatory network could reveal additional kinases involved in modulating sleep duration, potentially leading to novel drug targets and a deeper understanding of the brain's activity during sleep, including cognitive function and immune system maintenance.