SLC4A10 Gene – Sodium Bicarbonate Cotransporter 3 | NBCn2

SLC4A10 encodes the electroneutral sodium bicarbonate cotransporter NBCn2 (also known as NBC3). This protein mediates the coupled movement of Na+ and HCO3- across the plasma membrane, playing a critical role in intracellular pH homeostasis, particularly in neurons and epithelial cells. NBCn2 is essential for normal brain development and function; loss-of-function mutations cause autosomal recessive intellectual disability, epilepsy, and developmental delay. The transporter is also expressed in kidney, heart, and other tissues, contributing to acid-base balance.

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)

• pH regulation in neurons (KEGG: map04970)

NBCn2 (SLC4A10) is a 1089-amino acid transmembrane protein with 10-14 predicted helices. It functions as an electroneutral Na+/HCO3- cotransporter, importing Na+ and HCO3- with a 1:1 stoichiometry. The protein is highly expressed in brain, especially in neurons, where it regulates intracellular pH and modulates neuronal excitability. Structural studies reveal a conserved transporter fold with a central substrate-binding pocket. Mutations disrupting transport activity cause severe neurological phenotypes.