A Gain-of-function Mutation in the Gating Domain of ITPR1 Impairs Motor Movement and Increases Thermal and Mechanical Sensitivity

•The hyperactive ITPR1-D2594K mutation causes motor deficits and muscle weakness.•ITPR1 hyperactivity enhances the response to thermal and mechanical stimulation.•R-carvedilol attenuates the enhanced pain response in the ITPR1-D2594K mice.•The ITPR1-D2594K mutation has little effect on hippocampal learning and memory.