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SLC7A9
solute carrier family 7 member 9
SLC7A9 is located on the long (q) arm of chromosome 19, at band 19q13.11. Arm ratio per GRCh38 - banding schematic.
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Overview
SLC7A9 encodes one component of a heteromeric amino acid transporter predominantly expressed in the kidneys. This protein subunit works in partnership with a subunit encoded by SLC3A1 to form a functional transport complex embedded in kidney tubule cells. The complex specialises in reclaiming cystine, ornithine, arginine, and lysine from developing urine, returning these amino acids to the circulation. When pathogenic variants disrupt SLC7A9 function, the transporter complex cannot operate effectively, leading to excessive urinary loss of these amino acids and the formation of kidney stones containing cystine crystals.
Pathogenic variants in SLC7A9 follow an autosomal recessive inheritance pattern and represent a significant proportion of cystinuria cases worldwide. The gene is included on NHS Genomic Medicine Service panels for metabolic disorders and kidney stone conditions, reflecting its clinical relevance in the UK healthcare system.
What the gene does
The SLC7A9 protein functions as the light chain subunit of a heterodimeric amino acid transporter operating in the proximal tubule of the kidney. This transporter facilitates the reabsorption of dibasic amino acids and cystine from the glomerular filtrate, preventing their excretion in urine. The SLC7A9 subunit associates with the heavy chain encoded by SLC3A1 through a disulphide bond, creating a stable transporter complex at the apical membrane of renal epithelial cells.
The transporter operates as part of the body's mechanism for conserving essential amino acids during the filtration and concentration processes that produce urine. Cystine, ornithine, arginine, and lysine share structural features that allow them to be recognised by this transport system. Without functional SLC7A9, the kidney loses its capacity to reclaim these molecules efficiently, resulting in their accumulation in urine. Cystine has particularly low solubility at typical urine pH levels, making it prone to crystallisation when concentrations rise beyond the solubility threshold.
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Chromosome location
SLC7A9 is located on chromosome 19 at band q13.11. This chromosomal region contains numerous genes involved in metabolic and transport functions. The gene spans multiple exons encoding the 487-amino-acid protein product.
Protein structure
The SLC7A9 protein comprises 487 amino acids and includes a disordered region spanning amino acids 1 to 22 at the N-terminus. This disordered segment precedes the structured domains responsible for membrane integration and substrate recognition. The protein contains multiple transmembrane segments that anchor it within the cell membrane, positioning the transporter to facilitate amino acid movement across the epithelial barrier. The architecture enables formation of the heterodimeric complex with the SLC3A1 heavy chain, a configuration essential for transporter trafficking to the cell surface and catalytic activity.
Key variants
More than 95 pathogenic variants in SLC7A9 have been documented in association with cystinuria. These alterations include single-nucleotide changes, small insertions, and deletions that disrupt the reading frame or introduce premature termination signals. Missense variants affecting conserved residues within the transmembrane or substrate-binding regions can impair transporter assembly, membrane localisation, or catalytic function. The distribution of variants across the gene reflects the functional importance of multiple protein regions for maintaining effective amino acid reabsorption.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in SLC7A9 are primarily associated with cystinuria, an autosomal recessive condition characterised by impaired renal reabsorption of cystine and dibasic amino acids. Affected individuals experience recurrent kidney stone formation due to cystine crystallisation in acidic urine. Stone episodes can begin in childhood or early adulthood and may lead to chronic kidney disease if inadequately managed. The condition varies in severity, with some individuals experiencing frequent symptomatic stones requiring surgical intervention, whilst others have milder disease courses. SLC7A9-related cystinuria may also contribute to polygenic influences on chronic kidney disease risk in some contexts.
Inheritance pattern
Conditions caused by pathogenic SLC7A9 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
SLC7A9 appears on several NHS Genomic Medicine Service gene panels with green (high evidence) status. The gene is included in the Likely Inborn Error of Metabolism panel (R98), reflecting its role in amino acid transport disorders. It also features on the Nephrocalcinosis or Nephrolithiasis panel (R256), acknowledging its direct association with kidney stone formation. Additionally, SLC7A9 is part of the Undiagnosed Metabolic Disorders panel, supporting diagnostic evaluation in cases of unexplained metabolic presentations.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the SLC7A9 gene do?
SLC7A9 encodes a protein subunit that forms part of an amino acid transporter in the kidneys. This transporter reclaims cystine, ornithine, arginine, and lysine from developing urine, returning them to the bloodstream and preventing their loss from the body.
How is SLC7A9-related cystinuria inherited?
Cystinuria caused by SLC7A9 variants follows an autosomal recessive inheritance pattern. This means an individual must inherit pathogenic variants from both parents to develop the condition, whilst carriers with one variant typically remain asymptomatic.
Are SLC7A9 variants common in certain populations?
Cystinuria occurs across all populations, though carrier frequencies for SLC7A9 variants may vary by ancestry. Specific variants have been observed with higher frequency in particular ethnic groups, reflecting historical founder effects and population genetics.
References
- Font-Llitjós M, Jiménez-Vidal M, Bisceglia L. New insights into cystinuria: 40 new mutations, genotype-phenotype correlation, and digenic inheritance causing partial phenotype. Journal of medical genetics. 2005. PMID: 15635077
- Langman CB. The molecular basis of kidney stones. Current opinion in pediatrics. 2004. PMID: 15021200
- Goodyer P. The molecular basis of cystinuria. Nephron. Experimental nephrology. 2004. PMID: 15499206
- Schmidt C, Vester U, Wagner CA. Significant contribution of genomic rearrangements in SLC3A1 and SLC7A9 to the etiology of cystinuria. Kidney international. 2003. PMID: 14531788
- Fernández E, Carrascal M, Rousaud F. rBAT-b(0,+)AT heterodimer is the main apical reabsorption system for cystine in the kidney. American journal of physiology. Renal physiology. 2002. PMID: 12167606
- Dello Strologo L, Pras E, Pontesilli C. Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification. Journal of the American Society of Nephrology : JASN. 2002. PMID: 12239244
- Font MA, Feliubadaló L, Estivill X. Functional analysis of mutations in SLC7A9, and genotype-phenotype correlation in non-Type I cystinuria. Human molecular genetics. 2001. PMID: 11157794