SLC3A1 Gene – Cystinuria, Amino Acid Transport, and Clinical Significance

SLC3A1 encodes the heavy subunit (rBAT) of the heteromeric amino acid transporter responsible for the reabsorption of cystine and dibasic amino acids in the renal proximal tubule and small intestine. The protein forms a functional complex with light subunits (e.g., SLC7A9) via a disulfide bond. Defects in SLC3A1 cause cystinuria type I, an autosomal recessive disorder characterized by defective renal transport of cystine, ornithine, lysine, and arginine, leading to recurrent cystine kidney stones.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Amino acid transport across the plasma membrane (Reactome: R-HSA-352230)

• Transport of inorganic cations/anions and amino acids/oligopeptides (Reactome: R-HSA-425393)

• Cystinuria (KEGG: hsa05320)

The SLC3A1 protein (rBAT) is a type II membrane glycoprotein of 685 amino acids. It serves as the heavy subunit of the heteromeric amino acid transporter bo,+AT (with SLC7A9). rBAT is essential for the trafficking and functional expression of the light subunit at the apical membrane of renal and intestinal epithelial cells. The protein contains a single transmembrane domain, a large extracellular domain with a VWFA-like fold, and multiple N-glycosylation sites. Mutations that disrupt folding, trafficking, or disulfide bonding with the light subunit lead to cystinuria.