SLC4A1 Gene: Function, Mutations, and Associated Diseases | NCBI, OMIM, ClinVar

SLC4A1 encodes the band 3 anion exchange protein (AE1), the most abundant integral membrane protein in erythrocytes. It mediates the electroneutral exchange of chloride and bicarbonate across the plasma membrane, critical for CO2 transport and pH homeostasis. In the kidney, a truncated isoform (kAE1) is expressed in alpha-intercalated cells of the collecting duct, where it facilitates acid secretion. Mutations in SLC4A1 cause hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA). The gene also carries the Diego blood group antigens.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Erythrocyte membrane protein complex (Band 3-ankyrin-spectrin)

• Bicarbonate transport (SLC4 family)

• CO2 transport in erythrocytes

The SLC4A1 protein (AE1, band 3) is a 911-amino acid glycoprotein with two major domains: an N-terminal cytoplasmic domain (residues 1-403) that binds ankyrin, protein 4.1, and glycolytic enzymes, and a C-terminal membrane domain (residues 404-911) that forms the anion channel. The protein exists as a dimer in the erythrocyte membrane. In the kidney, a truncated isoform (kAE1, lacking exons 1-3) is expressed. Post-translational modifications include N-glycosylation at Asn642 and palmitoylation. The protein is essential for erythrocyte deformability and renal acid-base balance.