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.
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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. The current body of evidence comprises 1 study. EvidenceHub rates the overall confidence at 32/100 (low).
The Claim
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.
This conclusion is most relevant to: Healthy young adults (university students), 25 participants..
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Impact of Human Melanopsin Gene (OPN4) Polymorphisms (I394T, P10L) on Nocturnal Melatonin and Daily Rhythms in Young Adults. (Journal of pineal research, 2026) —
How It Works
The proposed biological pathway:
- ▸I394T variant alters melanopsin function in intrinsically photosensitive retinal ganglion cells
- ▸This affects the coupling between environmental light and downstream circadian outputs
- ▸Leads to phase delay in peripheral rhythms and reduced rhythm robustness
- ▸Results in lower nocturnal melatonin and altered light sensitivity
Who Might Benefit
Evidence fit by population:
- ▸Healthy young adults (university students), 25 participants.
Recommended Dose
N/A
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
References
- 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