Disease relevance of SLC7A9

• Cystinuria is discussed relative to mutations in SLC3A1 and SLC7A9 [1].
• Patients who inherit two mutant SLC7A9 genes have recurrent nephrolithiasis comparable to those with two rBAT mutations [2].

High impact information on SLC7A9

• Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT [3].
• We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus [3].
• Recently, the role of b(o,+)AT (SLC7A9) in cystinuria (non Type I) and the role of y(+)LAT-1 (SLC7A7) in lysinuric protein intolerance have been demonstrated [4].
• Mutations in SLC3A1, which encodes rBAT, cause Type I cystinuria, and mutations in SLC7A9, which encodes a putative subunit of rBAT (b(o,+)AT), cause non-Type I cystinuria [5].
• Here we describe the genomic structure of SLC7A9 (13 exons) and 28 new mutations in this gene that, together with the seven previously reported, explain 79% of the alleles in 61 non-Type I cystinuria patients [5].

Chemical compound and disease context of SLC7A9

• The finding of SLC7A9 mutations in all three subtypes underscores the complex interactions between specific cystinuria genes and other factors influencing cystine excretion [6].

Biological context of SLC7A9

• In 1999, the SLC7A9 (BAT1) gene was located on chromosome 19(19q13) by us and by a European group [7].
• Mutations G105R, V170M, A182T and R333W are the most frequent SLC7A9 missense mutations found [5].
• SLC7A9 mutations located in the putative transmembrane domains of b(o,+)AT and affecting conserved amino acid residues with a small side chain generate a severe phenotype, while mutations in non-conserved residues give rise to a mild phenotype [5].
• RESULTS: Two novel mutations were identified in SLC3A1 and three in SLC7A9; three were missense mutations and two frameshift mutations [8].
• Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Czech and Slovak cystinuric patients [9].

Associations of SLC7A9 with chemical compounds

• Mutations of SLC7A9, which encodes the luminal transport channel itself, tend to be dominant and mutations of SLC3A1 (rBAT), which encodes a transporter subunit, are always recessive [10].
• The genetic basis of the disorder is best characterized in humans and is caused by mutations in one of the amino acid transporter genes SLC3A1 or SLC7A9, which results in hyperexcretion of cystine and the dibasic amino acids in the urine and subsequent precipitation of cystine due to its low solubility in urine [11].

Other interactions of SLC7A9

• Identification of novel cystinuria mutations and polymorphisms in SLC3A1 and SLC7A9 genes: absence of SLC7A10 gene mutations in cystinuric patients [12].

Analytical, diagnostic and therapeutic context of SLC7A9

• METHODS: We screened a cohort of 49 cystinurics for copy number deviations in the genes SLC3A1 and SLC7A9 by quantitative real-time PCR assays using fluorogenic 5' nuclease chemistry [13].
• No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients' urinary pH [14].
• We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain TNF polymorphisms would be likely to yield positive associations if the true disease allele resided in LTA or BAT1 [15].

References