A de novo loss-of-function variant in the PER2 gene was observed in an ASD proabnd from the Simons Simplex Collection in Iossifov et al., 2014. Yuen et al., 2017 identified additional PER2 variants by whole genome sequencing in four ASD families, including a de novo LoF variant in a simplex family from the ASD: Genomes to Outcome Study cohort. Despite being a mutation-intolerant gene with a pLI score of 0.93, PER2 did not meet the statistical significance criteria used in Yuen et al., 2017 to be designated as an ASD candidate gene, which was a higher-than-expected mutation rate (false discovery rate < 15%).
Molecular Function
This gene is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
