SLC4A3 Gene - Anion Exchanger 3 (AE3) | Function, Mutations & Disease

SLC4A3 (Solute Carrier Family 4 Member 3) encodes the anion exchanger 3 (AE3) protein, a plasma membrane transporter that mediates electroneutral exchange of chloride (Cl⁻) for bicarbonate (HCO₃⁻). This exchange is critical for intracellular pH regulation, ion homeostasis, and cell volume control. AE3 is expressed predominantly in heart, brain, and skeletal muscle. Mutations in SLC4A3 have been associated with epilepsy, cardiac arrhythmias, and other disorders involving pH dysregulation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Bicarbonate transporters (Reactome: R-HSA-425393)

• Ion transport by P-type ATPases (Reactome: R-HSA-936837)

• Transport of inorganic ions/anions (Reactome: R-HSA-425407)

The AE3 protein (UniProt P48751) is a 1234-amino acid multi-pass transmembrane protein belonging to the anion exchanger family. It functions as a Cl⁻/HCO₃⁻ antiporter, exchanging extracellular chloride for intracellular bicarbonate. This activity is essential for maintaining pH and ion balance in excitable tissues such as brain and heart. AE3 exists in two splice variants: full-length (AE3) and cardiac-specific (AE3c). The protein contains a large cytoplasmic N-terminal domain and 12–14 transmembrane helices.