Defective SLC3A1 causes cystinuria (CSNU)

Defective SLC3A1 causes cystinuria (CSNU) Neutral and basic amino acid transport protein rBAT (SLC3A1) and b(0,+)-type amino acid transporter 1 (SLC7A9) are linked by a disulfide bridge to form system b(0,+)-like activity in the high affinity transport of neutral and dibasic amino acids and cystine. The SLC7A9:SLC3A1 heterodimer mediates the electrogenic exchange of extracellular amino acids such as L-arginine (L-Arg) and L-lysine (L-lys) and cystine (CySS-, the oxidised form of L-cysteine) for intracellular neutral amino acids such as L-leucine (L-Leu). These solute carriers are mainly expressed in the kidney and small intestine where they remove dibasic amino acids and cystine from the renal tubular and intestinal lumen respectively (Schweikhard & Ziegler 2012). Defects in SLC3A1 (or SLC7A9) can cause cystinuria (CSNU; MIM:220100), an autosomal recessive disorder characterised by impaired epithelial cell transport of cystine and dibasic amino acids in the proximal renal tubule and GI tract. The build-up and low solubility of cystine causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis and in severe cases, renal failure (Palacin et al. 2001, Mattoo & Goldfarb 2008, Fotiadis et al. 2013, Saravakos et al. 2014). Cystinuria is subcategorized as type A (mutations on SLC3A1) and type B (mutations on SLC7A9).