SPTAN1

The protein functions as a cytoskeletal scaffold protein that stabilizes the plasma membrane and organizes intracellular organelles, and is also involved in DNA repair and cell cycle regulation. Mutations cause a spectrum of autosomal dominant neurological disorders including developmental and epileptic encephalopathy, developmental delay with or without epilepsy, distal hereditary motor neuronopathy, and spastic paraplegia with or without cerebellar ataxia. The gene is highly intolerant to loss-of-function variants, and mutations can cause disease predominantly through haploinsufficiency, though the broad phenotypic spectrum suggests variant-dependent mechanisms may contribute.