Defective SLC12A6 causes agenesis of the corpus callosum, with peripheral neuropathy (ACCPN)

K+/Cl- cotransport is implicated not only in regulatory volume decrease, but also in transepithelial salt absorption, renal K+ secretion, myocardial K+ loss during ischemia and regulation of neuronal Cl- concentration. Four genes (SLC12A4-7) encode the K+/Cl- cotransporters KCC1-4 respectively. Cotransport of K+ and Cl- is electroneutral with a 1:1 stoichiometry. These cotransporters function as homomultimers or heteromultimers with other K+/Cl- cotransporters. SLC12A6 encodes KCC3 which is highly expressed in heart, brain, spinal cord, kidney, muscle, pancreas and placenta. Defects in SLC12A6 are a cause of agenesis of the corpus callosum with peripheral neuropathy (ACCPN; MIM:218000), a autosomal recessive disease characterised by severe progressive sensorimotor neuropathy, mental retardation, dysmorphic features and variable degree of agenesis of the corpus callosum.

Summary from Reactome (R-HSA-5619039), read 2026-09-23.