CSNK1D rs121912446: Understanding the FASPS2 Genetic Variant
The rs121912446 variant is a rare genetic change in the CSNK1D gene associated with Familial Advanced Sleep Phase Syndrome 2 (FASPS2). This condition causes individuals to have a significantly shifted circadian rhythm, leading to an early sleep and wake schedule.
What each genotype means
Typical circadian timing
You carry two copies of the standard reference allele for this position in the CSNK1D gene. You do not carry the rare Thr44Ala variant associated with familial advanced sleep phase syndrome type 2. Research suggests individuals with this genotype have typical baseline circadian regulation and kinase activity on period proteins.
Carried by virtually 100% of individuals across global populations.
Advanced sleep phase predisposition
You carry one copy of the rare missense variant (Thr44Ala) in the CSNK1D gene. Published research links this variant to familial advanced sleep phase syndrome type 2 (FASPS2), characterized by an early sleep-wake cycle and a high co-occurrence of migraine with or without aura. Evidence indicates this change reduces kinase activity on circadian regulatory proteins, though clinical expression within families can vary.
Extremely rare; identified only in private family pedigrees and absent or exceptionally rare across broad gnomAD populations.
Homozygous rare variant
You carry two copies of the Thr44Ala missense variant in the CSNK1D gene. Because this variant is inherited in an autosomal dominant manner and is extremely rare, homozygous individuals have not been documented in published clinical cohorts. Both copies of the gene are predicted to produce kinase enzymes with altered activity affecting circadian clock proteins.
Essentially zero; not reported in global population reference databases.
What is the rs121912446 Variant?
The rs121912446 variant is a specific change in the DNA sequence of the CSNK1D gene, often referred to in scientific literature as the Thr44Ala (T44A) mutation. This is a missense variant, meaning it results in a single amino acid substitution in the protein produced by the gene. Specifically, it replaces the amino acid threonine with alanine at position 44. This location is highly conserved across many species, suggesting that the protein's function at this site is biologically important. Because this variant is extremely rare and typically identified within specific families, it is considered a private familial variant rather than a common polymorphism found throughout the general population.
The Role of the CSNK1D Gene
The CSNK1D gene provides instructions for making an enzyme called casein kinase 1 delta (CK1δ). This enzyme acts as a protein kinase, a type of molecule that adds phosphate groups to other proteins to regulate their activity. CK1δ is a critical component of the body's internal biological clock, or circadian rhythm. It works by phosphorylating key clock proteins, such as those in the PERIOD (PER) family. By controlling the stability and degradation of these proteins, CK1δ helps determine the length and timing of the circadian cycle. Beyond sleep regulation, this enzyme is also involved in other essential cellular processes, including Wnt signaling, DNA damage response, and cell cycle progression.
Research and Clinical Associations
Research has linked the rs121912446 variant to Familial Advanced Sleep Phase Syndrome 2 (FASPS2), an autosomal dominant condition where individuals consistently fall asleep and wake up several hours earlier than the conventional time. Studies have shown that this specific mutation reduces the enzymatic activity of the CK1δ protein. This reduction in activity disrupts the normal phosphorylation of PER proteins, which effectively shortens the circadian period. Interestingly, some research has also observed a potential link between this variant and migraine with or without aura. In experimental models, the T44A mutation has been shown to increase sensitivity to migraine triggers and lower the threshold for cortical spreading depression, a physiological event associated with migraine aura. However, the evidence for this association remains limited to specific family studies.
Population Frequency and Interpretation
The rs121912446 variant is extremely rare in the general population, as documented in large-scale databases like gnomAD. Because it is a private familial variant, it is not typically found in the broader public. When interpreting genetic information, it is important to remember that the presence of a variant does not guarantee the development of a specific condition. Sleep patterns are complex and influenced by a combination of genetic, environmental, and social factors. If you have concerns about your sleep schedule or health, this information should be discussed with a qualified healthcare provider or a sleep specialist. They can provide a clinical evaluation that considers your personal and family medical history, which is far more informative than a single genetic result.
How common is this variant?
The rs121912446 variant is extremely rare in gnomAD and is primarily documented as a private familial variant.
Frequently asked questions
What is Familial Advanced Sleep Phase Syndrome 2?
FASPS2 is a rare, inherited sleep disorder characterized by a stable, advanced sleep-wake cycle. Affected individuals naturally fall asleep and wake up much earlier than the general population, often by several hours.
Can this variant cause migraines?
Some research suggests a potential link between CSNK1D mutations and migraine with aura. However, this association is based on limited family studies, and more research is needed to understand the connection.
Is this variant common?
No, this variant is extremely rare. It is typically identified as a private mutation within specific families rather than being a common variant found in the general population.
What should I do if I have this variant?
If you have received a report indicating you carry this variant, you should discuss the findings with a healthcare professional or a genetic counselor. They can help you interpret the results in the context of your personal health and family history.
Sources & further reading
Educational information only, last refreshed 10/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This missense mutation (Thr44Ala) in the CSNK1D gene is a known cause of familial advanced sleep phase syndrome (FASPS).
The T44A missense mutation in CSNK1D accelerates circadian period length and is linked to familial advanced sleep phase syndrome and migraine.
A rare missense variant (p.His205Arg) in CSNK1D causing familial advanced sleep phase syndrome type 2.
Exonic variant in CSNK1D; while some variants are linked to advanced sleep-wake phase syndrome, population-wide penetrance is often low.
This variant in CSNK1D is linked to familial advanced sleep phase syndrome, influencing circadian period length.
This variant is linked to advanced sleep phase syndrome, affecting the regulation of the circadian clock.