Solute carrier family 12 member 6 (SLC12A6 (KCC3))

Solute carrier family 12 member 6 (KCC3, SLC12A6) is an integral membrane protein responsible for the electroneutral co-transport of potassium (K⁺) and chloride (Cl⁻) ions across cell membranes, especially in neuronal and renal tissues. It functions in lowering intracellular chloride, regulating cell volume, and maintaining ionic balance, which are essential for signal transduction and neural excitability. KCC3 activity is tightly regulated by phosphorylation and cell volume states, is inactive under isotonic conditions, and is activated in response to cell swelling and hypotonicity. Mutations can cause severe neurological syndromes, including agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome), and SLC12A6 has also been associated with diverse neuropsychiatric and genetic disorders. KCC3 is a potential target for drugs aiming to treat sickle cell anemia, β-thalassemia, and neurological disorders, but no selective and approved drugs yet target this transporter clinically.

Other names

SLC12A6KCC3KCC3AKCC3BElectroneutral potassium-chloride cotransporter 3K-Cl cotransporter 3ACCPNCMT2IIpotassium chloride cotransporter 3potassium-chloride transporter-3apotassium-chloride transporter-3b

Drugs like furosemide block K-Cl cotransporter activity, reducing K⁺ and Cl⁻ efflux. Future therapies aim to modify transporter activity based on structural binding pockets revealed by cryo-EM