R150S mutation in the human oxytocin receptor: Gain-of-function effects and implication in autism spectrum disorder

This study investigates the rs547238576 (R150S) missense variant in the oxytocin receptor (OXTR) gene, previously observed through screening of rare variants in Japanese individuals with autism spectrum disorders (ASD). Contrary to the anticipated loss-of-function, R150S exhibits gain-of-function effects, enhancing oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca2+ mobilization in vitro. This suggests R150S may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD and other psychiatric disorders. Our findings underscore the significance of genetic variations in OXTR on functional activity and highlight the necessity for population-specific genetic study and in vitro analysis to elucidate genetic susceptibilities to neuropsychiatric conditions. •The rs547238576 (R150S) missense, a rare variant in the oxytocin receptor (OXTR) gene, was previously observed in Japanese individuals with autism spectrum disorders (ASD).•R150S OXTR exhibits gain-of-function effects: enhanced oxytocin (OXT) sensitivity, ligand-binding affinity, and OXT-induced Ca2+ mobilization in vitro.•These data suggests R150S variation may alter OXT signaling, potentially contributing to the excitatory/inhibitory imbalance seen in ASD.