Relevance to Autism

Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).

Molecular Function

This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes.

External Links

References