CLOCK T3111C (rs1801260): Circadian Gene

CLOCK (Circadian Locomotor Output Cycles Kaput) is a master regulator of circadian rhythms, the internal 24-hour cycles that govern sleep, metabolism, hormone release, and countless other biological processes. The T3111C variant (rs1801260) affects CLOCK expression and has been associated with evening chronotype, sleep differences, metabolic variations, and mood. Understanding your CLOCK genetics can help optimize your daily schedule and health habits.

Understanding Circadian Rhythms

Your body runs on an internal clock that influences nearly everything:

• Sleep-wake cycle: When you feel sleepy and alert
• Hormone release: Cortisol, melatonin, growth hormone timing
• Metabolism: When you burn vs. store energy
• Body temperature: Daily fluctuations
• Cognitive function: Peak mental performance times
• Cell repair: DNA repair, detoxification timing

The CLOCK Gene

CLOCK is central to the molecular clock mechanism:

• Forms a heterodimer with BMAL1 protein
• Activates expression of clock-controlled genes
• Creates ~24-hour oscillating gene expression patterns
• Master regulator in the suprachiasmatic nucleus (brain's clock)

The T3111C Variant

This variant is in the 3' untranslated region:

• T allele: Reference - typical circadian timing
• C allele: Associated with evening preference ("night owl")

Understanding Your Genotype

• T/T: More likely to be a morning person ("lark")
• T/C: Intermediate chronotype
• C/C: More likely to be an evening person ("owl")

Chronotype and Sleep

Evening Preference (C Allele)

• Naturally prefer later bedtimes and wake times
• Peak alertness later in the day
• May struggle with early morning schedules
• Often feel best in late afternoon/evening

Morning Preference (T/T)

• Naturally wake early and feel alert
• Peak performance earlier in the day
• May fade in the evening
• Easier time with conventional work schedules

Sleep Duration

• C allele associated with shorter sleep duration in some studies
• May have more difficulty falling asleep at conventional times
• Social jetlag more common (mismatch between biological and social clock)

Metabolic Implications

Circadian Metabolism

• Metabolism is tied to circadian rhythms
• Eating out of sync with your clock can promote weight gain
• Night owls forced to eat early may have worse metabolic outcomes

Obesity Risk

• C allele associated with higher BMI in some studies
• Evening eating patterns may contribute
• Social jetlag linked to metabolic dysfunction
• Relationship is complex - lifestyle factors matter greatly

Blood Sugar

• Glucose metabolism varies throughout the day
• Evening chronotypes may have impaired glucose tolerance when eating late
• Aligning meal timing with chronotype may improve metabolic health

Mood and Mental Health

Depression

• Circadian disruption linked to depression
• Some studies link C allele to depression risk
• Social jetlag may contribute to mood issues
• Evening types in morning-oriented society face challenges

Bipolar Disorder

• CLOCK variants studied in bipolar disorder
• Circadian disruption can trigger episodes
• Sleep schedule stability important for management

Seasonal Affective Disorder

• Circadian genes influence light sensitivity
• Evening types may be more susceptible
• Light therapy timing may need personalization

Optimizing for Your Chronotype

For Evening Types (C/C, T/C)

• If possible: Choose work/school schedules that start later
• Morning light: Get bright light exposure early to help shift rhythm earlier
• Evening light: Dim lights and avoid screens before bed
• Meal timing: Try to eat earlier even if not hungry; avoid late-night eating
• Exercise: Morning exercise can help shift circadian phase earlier
• Consistency: Keep regular schedule even on weekends to minimize social jetlag

For Morning Types (T/T)

• Take advantage of morning alertness for important tasks
• Schedule demanding work earlier in the day
• Protect evening wind-down time
• Be aware you may fade in evening social situations

Light Exposure Strategy

• Morning: Bright light (ideally sunlight) within 1 hour of waking
• Evening: Dim lights 2-3 hours before desired bedtime
• Blue light blocking: Glasses or screen filters in evening
• Light therapy box: Useful for shifting rhythm earlier

Supplements and Timing

Melatonin

• Can help shift circadian phase
• Low dose (0.5-3mg) 2-3 hours before desired sleep time
• Particularly helpful for evening types needing to sleep earlier

Medication Timing

• Many medications have optimal timing based on circadian rhythms
• Blood pressure, cholesterol, asthma medications affected
• Discuss chronotherapy with your healthcare provider

Prevalence

• C allele frequency: ~25-30% in most populations
• C/C genotype: ~7-10%
• Note: Chronotype also influenced by age, light exposure, and other genes

Testing with NutraHacker

NutraHacker's Complete Mutation Report analyzes CLOCK along with other genes affecting sleep and metabolism, helping you understand your circadian genetics.

Frequently Asked Questions

Can I change my chronotype?

Your genetic chronotype is your natural tendency, but it can be modified somewhat through light exposure, meal timing, and consistent sleep schedules. Evening types can shift earlier with morning light and evening light restriction. However, fighting your natural chronotype is difficult and may have health costs. When possible, aligning your schedule with your chronotype is healthier.

Why do I struggle with morning schedules if I'm C/C?

The C allele is associated with a later circadian phase - your internal clock runs later than the social clock. Early mornings mean you're trying to be alert when your body still thinks it's night. This creates "social jetlag" - a chronic mismatch between your biological and social schedules. Morning light exposure and consistent schedules can help shift your rhythm earlier.

Does this affect when I should eat?

Possibly. Eating in alignment with your circadian rhythm may improve metabolic health. Evening types who eat late (when their body is winding down) may have worse metabolic outcomes than if they ate the same food earlier. Try to avoid eating in the few hours before bed, even if you're naturally inclined to eat late.

References

1. Katzenberg D, et al. A CLOCK polymorphism associated with human diurnal preference. Sleep. 1998;21(6):569-576.
2. Monteleone P, et al. The 3111T/C polymorphism of the CLOCK gene is associated with diurnal preference and delayed sleep phase disorder in adolescents. J Biol Rhythms. 2008;23(6):536-542.
3. Garaulet M, et al. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. Int J Obes. 2010;34(3):516-523.