SLC12A5

The encoded protein is a neuronal potassium-chloride cotransporter that maintains low intracellular chloride levels required for proper GABA-mediated inhibition and is involved in dendritic spine formation and maturation. Mutations cause developmental and epileptic encephalopathy 34 and idiopathic generalized epilepsy through both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly intolerant to loss-of-function variants, and disease predominantly results from haploinsufficiency, though the dual inheritance patterns suggest variant-dependent mechanisms of pathogenicity.