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OPN4 – Delayed Sleep Phase Disorder

A single case report (PMID:36246649) provides evidence for an association between OPN4 and delayed sleep phase disorder. In this study, a male carrier was identified with a heterozygous missense variant, c.502C>T (p.Arg168Cys), which was functionally shown to disrupt melanopsin activity. The functional assay demonstrated that this variant renders the protein non‑functional, suggesting a loss‑of‑function pathogenic mechanism that disrupts normal circadian photoentrainment.

Overall, the available data support a limited gene‑disease relationship. Although the genetic evidence is restricted to a single proband, the experimental data provide supportive functional validation. This evidence, while preliminary, offers valuable insights for differential diagnosis and therapeutic decision‑making in patients with delayed sleep phase disorder.

References

  • Frontiers in Genetics • 2022 • Case report: A novel missense variant in melanopsin associates with delayed sleep phenotype: Whole genome sequencing study PMID:36246649

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Evidence is based on a single proband (PMID:36246649) with functional data supporting a pathogenic role.

Genetic Evidence

Limited

Only one missense variant, c.502C>T (p.Arg168Cys), has been reported in the context of DSWPD without additional familial segregation data (PMID:36246649).

Functional Evidence

Moderate

In vitro studies demonstrated that the p.Arg168Cys variant abolishes melanopsin function, consistent with a loss‑of‑function mechanism (PMID:36246649).