HormonesMelatonin

The OPN4 I394T variant (C allele) is associated with altered non-image-forming physiology in young adults, including phase-delayed rhythms, reduced rhythm robustness, and lower nocturnal melatonin levels.

In 25 healthy young adults, carriers of the I394T-C allele showed a phase delay in habitual sleep and wrist temperature rhythms, reduced wrist temperature amplitude, greater internal desynchronization, and lower nocturnal melatonin concentrations under dim light compared to the TT group. Circadian phase (DLMO) remained preserved, leading to an increased phase angle of entrainment, and on free days they showed greater melatonin suppression despite similar light exposure.

Last updated: Aug 22, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Impact of Human Melanopsin Gene (OPN4) Polymorphisms (I394T, P10L) on Nocturnal Melatonin and Daily Rhythms in Young Adults.

observational

Vicente-Martínez J, Bonmatí-Carrión MÁ, López-Parra AM, Madrid JA, Almaida-Pagán PF, Rol MA · Journal of pineal research (2026)

Participants: N/A
Duration: 8 days
Intervention: Genotyping of OPN4 SNPs (I394T and P10L) with analysis under dominant models; no intervention was applied.
Outcome: Nocturnal melatonin concentrations, dim light melatonin onset (DLMO), wrist temperature rhythm amplitude and phase, sleep timing, activity, light exposure, pupillary light reflex, phase angle of entrainment, internal desynchronization.
Effect Size: N/A
Population: Healthy young adults (university students), 25 participants.

Result:

PubMed: 42578404DOI: 10.1111/jpi.70181

Mechanism Graph

I394T variant alters melanopsin function in intrinsically photosensitive retinal ganglion cells
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This affects the coupling between environmental light and downstream circadian outputs
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Leads to phase delay in peripheral rhythms and reduced rhythm robustness
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Results in lower nocturnal melatonin and altered light sensitivity

Limitations

  • ⚠Small sample size (n=25) limits statistical power and generalizability
  • ⚠Observational genetic association study; causality cannot be established
  • ⚠Real-world conditions may introduce confounding variables (e.g., light exposure variability, lifestyle differences)

Frequently Asked Questions

What is the I394T variant in the OPN4 gene?▼

I394T (rs1079610) is a missense single nucleotide polymorphism in the human melanopsin gene OPN4, where isoleucine is replaced by threonine at position 394. This study found that carriers of the C allele (I394T-C) exhibit altered circadian and melatonin responses.

How does the I394T variant affect melatonin levels?▼

Carriers of the I394T-C allele had lower nocturnal melatonin concentrations under dim light compared to non-carriers, and on free days they showed greater melatonin suppression in response to light, despite similar light exposure.

Does the I394T variant affect circadian phase?▼

The study found that while habitual sleep and wrist temperature rhythms were phase-delayed, the circadian phase (DLMO) remained preserved, resulting in an increased phase angle of entrainment. This suggests the variant affects the coupling between light and circadian outputs rather than the central clock itself.

Is the P10L variant associated with any effects?▼

No, the P10L variant (T allele) was not associated with significant differences in ambulatory, hormonal, or pupillary outcomes in this study.

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References

  1. 1.Vicente-Martínez J, Bonmatí-Carrión MÁ, López-Parra AM, Madrid JA, Almaida-Pagán PF, Rol MA. "Impact of Human Melanopsin Gene (OPN4) Polymorphisms (I394T, P10L) on Nocturnal Melatonin and Daily Rhythms in Young Adults.." Journal of pineal research, 2026. PMID: 42578404 DOI: 10.1111/jpi.70181
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.