PER2 rs121908635: Understanding Familial Advanced Sleep Phase
The rs121908635 variant in the PER2 gene is a rare genetic mutation associated with Familial Advanced Sleep Phase Syndrome (FASPS1). Individuals with this variant typically experience a significantly advanced sleep-wake cycle, characterized by early evening sleep onset and early morning awakening.
What each genotype means
Typical circadian rhythm
This is the common, wild-type genotype for the PER2 gene at this position. Individuals with this genotype do not carry the specific mutation associated with Familial Advanced Sleep Phase Syndrome 1 (FASPS1).
This is the most common genotype found in the general population.
Familial advanced sleep phase
This genotype represents a heterozygous state for the p.Ser662Gly (often cited as p.Ser663Gly) mutation. This variant is associated with Familial Advanced Sleep Phase Syndrome 1 (FASPS1), a condition characterized by an advanced sleep-wake cycle where individuals naturally wake up and go to sleep significantly earlier than the general population. Please discuss your sleep patterns and any concerns regarding circadian rhythm with a healthcare provider or sleep specialist.
This genotype is extremely rare and is typically identified only in families affected by this specific sleep disorder.
Familial advanced sleep phase
This genotype represents a homozygous state for the p.Ser662Gly mutation. While FASPS1 is typically described as an autosomal dominant trait, individuals with this genotype carry two copies of the variant associated with an advanced sleep-wake cycle. Please consult with a sleep specialist to discuss how this may influence your circadian rhythm and overall sleep health.
This genotype is exceptionally rare and has not been widely reported in general population databases.
What is the rs121908635 Variant?
The variant rs121908635 is a specific genetic change located within the PER2 gene on chromosome 2. In scientific literature, this is often referred to as a missense mutation, specifically p.Ser663Gly (sometimes noted as p.Ser662Gly depending on the protein isoform). This change involves a single nucleotide substitution that alters the amino acid sequence of the PER2 protein. Because this variant is extremely rare in the general population, it is primarily studied in the context of specific families who exhibit a clear, inherited pattern of advanced sleep timing. It is not a common variant found in the general population, but rather a private familial mutation that has been instrumental in helping researchers understand the molecular mechanisms that govern the human internal biological clock.
The Role of the PER2 Gene
The PER2 gene encodes the Period Circadian Protein Homolog 2, which is a critical component of the molecular machinery that regulates circadian rhythms in humans. These rhythms are the internal processes that drive our 24-hour sleep-wake cycle, body temperature fluctuations, and hormone release, such as melatonin. The PER2 protein functions as part of a feedback loop that oscillates over approximately 24 hours. When this protein is functioning normally, it helps the body synchronize its internal time with the external environment. Mutations in this gene, such as rs121908635, can disrupt this delicate feedback loop. Specifically, this variant has been shown to reduce the efficiency of phosphorylation by certain enzymes, which effectively shortens the period of the circadian clock, leading to the characteristic 'advanced' timing observed in affected individuals.
Research and Clinical Associations
Research has strongly associated the rs121908635 variant with Familial Advanced Sleep Phase Syndrome (FASPS1). FASPS is a rare, inherited condition where an individual's sleep-wake cycle is shifted several hours earlier than the conventional norm. Affected individuals often feel the urge to sleep in the early evening and wake up very early in the morning, often before they desire to do so. The evidence for this association is considered robust within the context of the families studied, as the trait follows an autosomal dominant inheritance pattern. This means that inheriting a single copy of the variant from one parent is sufficient to manifest the sleep phase advance. While this variant is a well-documented cause of FASPS, it is important to note that not all sleep phase issues are caused by this specific mutation; other genes and environmental factors also play significant roles in sleep regulation.
Understanding Your Information
If you have information regarding this variant, it is important to understand that this is a rare, highly specific genetic finding. This information is for educational purposes and should not be used for self-diagnosis or medical decision-making. Because FASPS is a complex condition that can be influenced by various genetic and environmental factors, any concerns regarding sleep patterns should be discussed with a qualified healthcare provider or a sleep specialist. They can provide a clinical evaluation, which may include sleep logs, actigraphy, or melatonin rhythm testing, to determine the cause of sleep disturbances. Never attempt to alter your sleep schedule or use medications based on genetic data without professional medical guidance. Genetic testing results are only one piece of a much larger clinical picture, and a professional can help you interpret what this means for your health and well-being.
How common is this variant?
The rs121908635 variant is extremely rare, with a frequency of less than 0.0001 in the gnomAD database, characterizing it as a private familial mutation.
Frequently asked questions
What is Familial Advanced Sleep Phase Syndrome?
FASPS is a rare, inherited sleep disorder where an individual's internal clock is set several hours earlier than normal. People with this condition typically fall asleep in the early evening and wake up very early in the morning.
Is rs121908635 the only cause of early sleep timing?
No, while this variant is a known cause of FASPS1, many other factors influence sleep timing. Other genes, such as CSNK1D and PER3, as well as environmental and lifestyle factors, can also contribute to advanced sleep phase.
How is this variant inherited?
This variant follows an autosomal dominant inheritance pattern. This means that an individual only needs to inherit one copy of the variant from one biological parent to potentially exhibit the advanced sleep phase trait.
Should I get tested for this variant?
Genetic testing for rare variants is typically only performed in a clinical setting when there is a strong family history of a specific condition. You should discuss any concerns about your sleep patterns with a doctor before seeking genetic testing.
Sources & further reading
Educational information only, last refreshed 9/18/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Pathogenic missense variant (Ser662Gly) in PER2 that impairs casein kinase phosphorylation, causing familial advanced sleep phase syndrome (FASPS-1).
This intronic variant in the PER2 gene is associated with individual differences in circadian rhythm, sleep timing, and chronotype.
Common missense/synonymous tagging variant in core clock gene PER2 modulating eveningness preference and diurnal phase delay.
Variant in the circadian regulator PER2 associated with circadian rhythm phase, chronotype, and timing of habitual sleep.
This variant is associated with familial advanced sleep phase syndrome, affecting the timing of the sleep-wake cycle.
A mutation in the PER2 gene associated with familial advanced sleep phase syndrome, leading to an earlier sleep-wake cycle.