Natural short sleepers have a genetic mutation, finds new study

Not everyone needs 8 hours of sleep to function properly. Some people can feel well-rested and show no negative effects of sleep deprivation, even after just 4 hours of sleep, which is likely the result of a genetic mutation.

A recent study has reported that a mutation in salt-induced kinase 3 (hSIK3-N783Y)—a gene critical for regulating sleep duration and depth—may be the reason why some people are natural short sleepers (NSS).

The findings of this study are published in Proceedings of the National Academy of Sciences.

We might be physically inactive when sleeping, but our body is far from being idle. It goes into servicing mode, repairing cells, replenishing essential hormones and facilitating neural reorganization.

As a result, sleep deprivation can significantly impair both physical and cognitive functioning. Over time, chronic sleep loss may even raise the risk of serious health issues such as heart disease, diabetes, stroke, obesity, and depression. Hence, it is medically advised to sleep for at least 7–9 hours to maintain good physical and mental health.

Natural short sleepers seem to bypass all these negative outcomes of sleep deprivation with only 4–6 hours of sleep per night, and sleeping beyond that can sometimes make them feel worse. Previous studies have identified five mutations in four genes—DEC2, ADRB1, NPSR1, and GRM1—that have been linked to the natural short sleep (NSS) trait in humans.

It has also been found that intracellular signaling pathways of protein kinases—enzymes catalyzing the transfer of phosphate groups from ATP to other proteins—such as salt-inducible kinase 3 (Sik3), play a key role in regulating sleep and wakefulness. However, there was a lack of direct evidence of their role in regulating NSS traits.

To better understand its role, the researchers first recruited a natural short sleeper, a healthy 70-year-old volunteer with a lifelong active lifestyle. Her self-reported habitual sleep-wake patterns were obtained through a structured interview, and her sleep patterns were recorded using wrist actigraphy.

They observed that while the volunteer self-reported 3 hours of sleep per day, the actigraphy recordings indicated an average of 6.3 hours of sleep per night.

The team also collected her DNA samples to perform whole-exome sequencing and identify genetic variants that could give rise to her NSS trait. The analysis indicated a point mutation, N783Y, in the SIK3 protein kinase.

To confirm that the SIK3-N783Y mutation causes the short sleep trait, the scientists generated the same mutation in a mouse model and found that the mutant mice slept 30 minutes less compared to other mice.

Computational analysis showed that the point mutation caused significant structural changes in the SIK3 protein, impairing its ability to transfer phosphate molecules to other proteins and resulting in reduced sleep duration.

Understanding the genetics of sleeping behaviors can help design treatment strategies for improving sleep quality and mitigating the effects of sleep deprivation in the general population. The researchers note that the findings underscore the evolutionary conservation of SIK3 as a sleep gene and its potential as a therapeutic target for sleep disorders.

© 2025 Science X Network

Not everyone needs 8 hours of sleep to function properly. Some people can feel well-rested and show no negative effects of sleep deprivation, even after just 4 hours of sleep, which is likely the result of a genetic mutation.

A recent study has reported that a mutation in salt-induced kinase 3 (hSIK3-N783Y)—a gene critical for regulating sleep duration and depth—may be the reason why some people are natural short sleepers (NSS).

The findings of this study are published in Proceedings of the National Academy of Sciences.

We might be physically inactive when sleeping, but our body is far from being idle. It goes into servicing mode, repairing cells, replenishing essential hormones and facilitating neural reorganization.

As a result, sleep deprivation can significantly impair both physical and cognitive functioning. Over time, chronic sleep loss may even raise the risk of serious health issues such as heart disease, diabetes, stroke, obesity, and depression. Hence, it is medically advised to sleep for at least 7–9 hours to maintain good physical and mental health.

Natural short sleepers seem to bypass all these negative outcomes of sleep deprivation with only 4–6 hours of sleep per night, and sleeping beyond that can sometimes make them feel worse. Previous studies have identified five mutations in four genes—DEC2, ADRB1, NPSR1, and GRM1—that have been linked to the natural short sleep (NSS) trait in humans.

It has also been found that intracellular signaling pathways of protein kinases—enzymes catalyzing the transfer of phosphate groups from ATP to other proteins—such as salt-inducible kinase 3 (Sik3), play a key role in regulating sleep and wakefulness. However, there was a lack of direct evidence of their role in regulating NSS traits.

To better understand its role, the researchers first recruited a natural short sleeper, a healthy 70-year-old volunteer with a lifelong active lifestyle. Her self-reported habitual sleep-wake patterns were obtained through a structured interview, and her sleep patterns were recorded using wrist actigraphy.

They observed that while the volunteer self-reported 3 hours of sleep per day, the actigraphy recordings indicated an average of 6.3 hours of sleep per night.

The team also collected her DNA samples to perform whole-exome sequencing and identify genetic variants that could give rise to her NSS trait. The analysis indicated a point mutation, N783Y, in the SIK3 protein kinase.

To confirm that the SIK3-N783Y mutation causes the short sleep trait, the scientists generated the same mutation in a mouse model and found that the mutant mice slept 30 minutes less compared to other mice.

Computational analysis showed that the point mutation caused significant structural changes in the SIK3 protein, impairing its ability to transfer phosphate molecules to other proteins and resulting in reduced sleep duration.

Understanding the genetics of sleeping behaviors can help design treatment strategies for improving sleep quality and mitigating the effects of sleep deprivation in the general population. The researchers note that the findings underscore the evolutionary conservation of SIK3 as a sleep gene and its potential as a therapeutic target for sleep disorders.

© 2025 Science X Network