TIMELESS rs28936676: Circadian Rhythm and Sleep Phase
The rs28936676 variant is a rare missense mutation located within the TIMELESS gene. It has been scientifically implicated in familial advanced sleep phase syndrome, a condition characterized by an early shift in the body's internal circadian clock.
What each genotype means
Typical circadian timing
You carry two copies of the common reference allele at this position in the TIMELESS gene. This genotype is not associated with monogenic advanced sleep phase or altered circadian timing. Your natural sleep-wake patterns are influenced primarily by common polygenic factors and environmental habits.
Carried by the vast majority of people worldwide, exceeding 99.9% across all major continental populations.
Possible early sleep tendency
You carry one copy of the rare missense variant in the TIMELESS gene, which has been evaluated in pedigrees for familial advanced sleep phase type. However, large population-based cohort studies indicate that penetrance in the general population is limited and the actual effect on daily sleep timing may be subtle or negligible. This result is descriptive of a statistical finding and is not a clinical diagnosis of a circadian rhythm sleep disorder.
Extremely rare; observed in fewer than 1 in 10,000 individuals in large multi-ancestry sequencing databases such as gnomAD.
Extremely rare variant homozygote
You carry two copies of the rare alternative allele in the TIMELESS gene. Because this variant is exceptionally scarce in the general population, homozygous individuals are essentially uncharacterized in clinical literature. The precise circadian consequences remain uncertain, though research points toward modest or variable shifts in sleep timing rather than severe monogenic effects.
Virtually absent in public reference cohorts, with estimated population frequencies well below 1 in 1,000,000 individuals.
Understanding the rs28936676 Variant
The rs28936676 variant is a specific change in the DNA sequence of the TIMELESS gene. In genetics, a missense variant occurs when a single nucleotide change results in the substitution of one amino acid for another in the final protein product. This specific variant is categorized as rare, meaning it is not commonly found in the general population. It sits within the coding region of the TIMELESS gene, which provides instructions for creating a protein essential for maintaining the body's internal biological clock. Because this variant alters the structure of the TIMELESS protein, researchers have investigated whether it disrupts the normal molecular feedback loops that govern our daily sleep-wake cycles. Understanding such variants helps scientists map the complex genetic architecture that influences human sleep behavior and circadian timing.
The Role of the TIMELESS Gene
The TIMELESS gene, also known as the timeless circadian regulator, plays a critical role in the autoregulatory loop of the human circadian clock. The protein it encodes interacts with other key clock proteins, such as the PERIOD (PER) family, to regulate the timing of gene expression throughout the day. By modulating the activity of these proteins, TIMELESS helps ensure that physiological processes—such as sleep onset, hormone release, and body temperature regulation—align with the 24-hour solar cycle. Beyond its circadian functions, the TIMELESS protein is also involved in other cellular processes, including DNA repair and cell cycle regulation. Because of its central position in the circadian machinery, mutations in this gene can have significant impacts on how an individual's internal clock responds to environmental cues like light and darkness.
Research and Evidence Strength
Research linking rs28936676 to familial advanced sleep phase syndrome (FASPS) is based on studies of specific families exhibiting this trait. FASPS is a rare condition where individuals consistently fall asleep and wake up several hours earlier than the societal norm. Published research, including studies in the Proceedings of the National Academy of Sciences, has demonstrated that this mutation can lead to the cytoplasmic accumulation of the TIMELESS protein, which in turn alters phase responsiveness. While the evidence strongly suggests a functional impact on circadian timing in the affected families, the overall evidence strength for this variant in the broader population remains limited. It is important to note that sleep patterns are polygenic, meaning they are influenced by many different genes and environmental factors, not just a single variant.
Population Frequency and Interpretation
The rs28936676 variant is extremely rare. According to data from the Genome Aggregation Database (gnomAD), the minor allele frequency in European non-Finnish populations is less than 0.0001. This low frequency confirms that the variant is not a common feature of the human genome but rather a rare occurrence that may be specific to certain lineages or families. Because of its rarity, most people will not carry this variant. For those who do, it is essential to understand that genetic associations are not diagnostic. Having a specific genotype does not guarantee that an individual will experience advanced sleep phase or any other sleep disorder. Sleep health is complex, and individuals concerned about their sleep patterns should consult with a healthcare professional or a sleep specialist to discuss their symptoms and potential management strategies.
How common is this variant?
The rs28936676 variant is very rare, with a minor allele frequency of less than 0.0001 in European non-Finnish populations according to gnomAD.
Frequently asked questions
What is familial advanced sleep phase syndrome?
Familial advanced sleep phase syndrome is a rare condition where an individual's internal clock is set to an earlier time than normal. People with this condition typically feel sleepy in the early evening and wake up very early in the morning, often before they intend to.
Does having this variant mean I have a sleep disorder?
No, having a genetic variant does not mean you have a medical condition. Sleep patterns are influenced by many factors, and genetic associations are statistical observations rather than clinical diagnoses.
Can I use this information to change my sleep schedule?
Genetic information should not be used to self-diagnose or alter medical treatment. If you are struggling with your sleep schedule, please consult a doctor or a sleep specialist for personalized advice.
Is the TIMELESS gene only involved in sleep?
No, the TIMELESS protein is multifunctional. While it is a key component of the circadian clock, it also plays roles in other cellular processes such as DNA repair and cell cycle regulation.
Sources & further reading
Educational information only, last refreshed 10/12/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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