rs2304672 — PER2 5'UTR C111G

Regulatory variant in a core clock gene that influences circadian timing, sleep-wake preference, and reward processing

See your personal result for PER2

Upload your DNA data to find out which genotype you carry and what it means for you.

Upload your DNA data

Works with 23andMe, AncestryDNA, and other DNA test exports. Results in under 60 seconds.

PER2 C111G — Your Internal Clock's Fine-Tuning Dial

The PER2 gene is one of the central gears in your body's circadian clock11 circadian clock
The ~24-hour internal timer that governs sleep-wake cycles, hormone release, body temperature, and metabolism. It runs in nearly every cell but is coordinated by the suprachiasmatic nucleus (SCN) in the brain. Every day, PER2 protein levels rise and fall in a precise rhythm: the protein accumulates, enters the nucleus to shut down its own gene, gets degraded, and the cycle starts again. This molecular oscillation is the heartbeat of circadian timing. The rs2304672 variant sits in the 5' UTR22 5' UTR
5' untranslated region: the stretch of mRNA before the protein-coding sequence begins. It doesn't change the protein itself but can alter how much protein gets made and when of PER2, 12 bases upstream of where translation begins, positioning it to influence how much PER2 protein your cells produce.

The Mechanism

Unlike the famous PER2 S662G mutation that causes Familial Advanced Sleep Phase Syndrome33 Familial Advanced Sleep Phase Syndrome
FASPS: a rare inherited condition where affected individuals fall asleep around 7:30 PM and wake at 4:30 AM. Caused by a missense mutation that alters PER2 phosphorylation and degradation, rs2304672 does not change the PER2 protein itself. Instead, it sits in the 5' UTR regulatory region where it can affect mRNA stability, translation efficiency, or transcription factor binding. The C allele (plus strand; called "111G" in the original literature, which used mRNA strand notation44 mRNA strand notation
PER2 is on the minus strand of chromosome 2. The "C111G" name describes the change on the mRNA/coding strand: C (common) to G (variant). On the plus strand that 23andMe reports, this is reversed: G (common) to C (variant)) has been associated with lower PER2 expression in thyroid tissue, suggesting it may subtly reduce PER2 protein levels. Since PER2 is a transcriptional repressor55 transcriptional repressor
PER2 protein accumulates and then enters the nucleus where it inhibits CLOCK/BMAL1, the transcription factors that activated PER2 in the first place. This negative feedback loop is the core engine of the circadian clock in the clock feedback loop, reduced levels could advance the phase of the oscillation, shifting the entire sleep-wake cycle earlier.

The Evidence

The original discovery66 original discovery
Carpen JD et al. A single-nucleotide polymorphism in the 5'-untranslated region of the hPER2 gene is associated with diurnal preference. J Sleep Res, 2005 came from a UK study at the University of Surrey. Among 484 volunteers screened for extreme chronotype, the C allele (plus strand) was found at 14% frequency in extreme morning types but only 3% in extreme evening types (OR 5.67, P = 0.031). This made rs2304672 one of the first common variants linked to human chronotype.

Replication has been mixed. A Korean study of 299 medical students77 Korean study of 299 medical students
Lee HJ et al. PER2 variation is associated with diurnal preference in a Korean young population. Behav Genet, 2011 found no significant association, though the authors noted the minor allele frequency was very low in their East Asian sample (8.4%), limiting statistical power. A Swedish study of over 1,200 individuals88 Swedish study of over 1,200 individuals
Johansson AS et al. PER gene family polymorphisms in relation to cluster headache and circadian rhythm in Sweden. Brain Sci, 2021 found a minor allele frequency of ~12% in European controls but no association with cluster headache or chronotype in that cohort.

Beyond chronotype, neuroimaging research in 90 adolescents99 neuroimaging research in 90 adolescents
Forbes EE et al. PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry activity in adolescents. Biol Psychiatry, 2012 revealed that C allele carriers showed reduced medial prefrontal cortex1010 medial prefrontal cortex
mPFC: a brain region involved in reward evaluation, decision-making, and emotional regulation. It integrates circadian signals with motivational states activity during reward processing, and this effect was modulated by sleep timing. Later sleep midpoints amplified the difference between genotypes, suggesting that the variant's impact on brain function depends on alignment with circadian phase.

A UK twin study of 862 participants1111 UK twin study of 862 participants
Denis D et al. A twin and molecular genetics study of sleep paralysis and associated factors. J Sleep Res, 2015 found a nominally significant association between rs2304672 and sleep paralysis (P = 0.008, additive model), though this did not survive correction for multiple testing. The connection is plausible: sleep paralysis involves dysregulated transitions between sleep stages, which are under circadian control.

Practical Implications

This variant has a modest effect size and mixed replication, placing it firmly in the "worth knowing, not life-changing" category. If you carry one or two copies of the C allele, you may have a natural tendency toward earlier sleep timing. This is not deterministic: light exposure, meal timing, exercise, and social schedule all powerfully shape your circadian phase. But working with your genetic tendency rather than against it can improve sleep quality and daytime alertness.

The reward circuitry findings suggest that C allele carriers may be more sensitive to the cognitive effects of misaligned sleep. If you are a carrier who keeps a late schedule (fighting your biological clock), you may notice stronger effects on mood and motivation than a non-carrier would in the same situation.

Interactions

PER2 operates within a network of clock genes. CLOCK (rs1801260) drives PER2 transcription as part of the CLOCK/BMAL1 activator complex, while PER3 (rs57875989) is a paralog with its own circadian associations. Carriers of both the PER2 rs2304672 C allele and the CLOCK rs1801260 G allele (evening preference allele) may experience a push-pull effect on chronotype, with the net result depending on which signal dominates. Studies examining these variants together are limited but the biological rationale for interaction is strong, given that PER2 and CLOCK sit on opposite sides of the same feedback loop.

Genotype Interpretations

What each possible genotype means for this variant.

GG Typical Clock Timing Normal

Standard PER2 expression and typical circadian timing

The GG genotype at rs2304672 represents the reference sequence in the 5' UTR of PER2. Population studies show this is the most common genotype across all ancestries, ranging from about 78% in South Asian populations to over 92% in Latino populations. With standard PER2 regulatory sequence, your circadian clock timing at this locus is neutral — neither pushed toward morningness nor eveningness by this particular variant.

CG Carrier — Morning Shift Intermediate

One copy of the morning-preference allele; mildly shifted circadian timing

Heterozygous carriers of the PER2 5'UTR C allele were included in the group showing a 5.67-fold higher odds of extreme morning preference in the original Carpen et al. 2005 study. The C allele is associated with subtly reduced PER2 expression, which may advance the phase of the molecular clock. Neuroimaging research suggests carriers also show altered reward circuitry responses that are modulated by sleep timing, meaning the variant's functional impact may be amplified when your sleep schedule is misaligned with your biology. The association with sleep paralysis (P = 0.008 in a UK twin study) suggests this variant may also influence sleep stage transitions.

CC Morning-Shifted Clock High

Two copies of the morning-preference allele; stronger circadian advance

The CC genotype represents homozygosity for the minor allele at rs2304672. While rare (approximately 1% globally, though somewhat more common in South Asian populations at ~2%), this genotype is associated with the strongest morning-preference signal at this locus. Expression data from thyroid tissue shows the CC genotype has lower PER2 expression than G carriers, consistent with an advanced circadian phase. The 2005 Carpen study found the C allele at 14% frequency in extreme morning types versus 3% in extreme evening types. The rarity of CC homozygotes means most studies group them with CG heterozygotes, so the specific effect size for CC alone is not well characterized, but it is expected to be stronger than the heterozygous state given the codominant pattern.

The Forbes et al. neuroimaging study found that C allele carriers showed reduced medial prefrontal cortex activity during reward processing, with effects amplified by later sleep timing. For CC homozygotes keeping a late schedule, this mismatch may be particularly impactful.