biostudies-literatureMoldenhauer HJNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNational Institute of General Medical SciencesNIGMS NIH HHS404-413https://www.ebi.ac.uk/biostudies/studies/S-EPMC9531041biostudies-literatureUnknown5BK K⁺ channels are critical regulators of neuron and muscle excitability, comprised of a tetramer of pore-forming αsubunits from the <i>KCNMA1</i> gene and cell- and tissue-selective β subunits (<i>KCNMB1-4</i>). Mutations in <i>KCNMA1</i> are associated with neurological disorders, including autism. However, little is known about the role of neuronal BK channel β subunits in human neuropathology. The β2 subunit is expressed in central neurons and imparts inactivation to BK channels, as well as altering activation and deactivation gating. In this study, we report the functional effect of G124R, a novel <i>KCNMB2</i> mutation obtained from whole-exome sequencing of a patient diagnosed with autism spectrum disorder. Residue G124, located in the extracellular loop between TM1 and TCurrent research in physiologyEffect of an autism-associated <i>KCNMB2</i> variant, G124R, on BK channel properties.PMC9531041T32-GM008181R01-HL102758R01 HL102758T32 GM008181Fernandez-Jaen AMoldenhauer HJMeredith ALDinsdale RLAlvarez SfalseEffect of an autism-associated <i>KCNMB2</i> variant, G124R, on BK channel properties.BK K⁺ channels are critical regulators of neuron and muscle excitability, comprised of a tetramer of pore-forming αsubunits from the <i>KCNMA1</i> gene and cell- and tissue-selective β subunits (<i>KCNMB1-4</i>). Mutations in <i>KCNMA1</i> are associated with neurological disorders, including autism. However, little is known about the role of neuronal BK channel β subunits in human neuropathology. The β2 subunit is expressed in central neurons and imparts inactivation to BK channels, as well as altering activation and deactivation gating. In this study, we report the functional effect of G124R, a novel <i>KCNMB2</i> mutation obtained from whole-exome sequencing of a patient diagnosed with autism spectrum disorder. Residue G124, located in the extracellular loop between TM1 and T2022-01-01T00:00:00Z20222025-04-22T21:53:56.349Z2025-02-19T01:28:26.584ZS-EPMC95310413620381710.1016/j.crphys.2022.09.001