X-linked recessive nephrolithiasis with renal failure: genes and variants
X-linked recessive nephrolithiasis with renal failure is linked to 1 analyzed protein (CLCN5). 3 DNA variants are known to cause it; 17 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to X-linked recessive nephrolithiasis with renal failure
CLCN5: H(+)/Cl(-) exchange transporter 5
It supports endosomal acidification and receptor recycling in renal proximal-tubule cells, enabling efficient reabsorption of filtered proteins and solutes. Loss-of-function variants cause Dent disease type 1, with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, and kidney-stone risk.
3 disease-causing and 17 uncertain variants in CLCN5 are linked to X-linked recessive nephrolithiasis with renal failure.
Known disease-causing variants in X-linked recessive nephrolithiasis with renal failure
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CLCN5 S314L | 314 | Helical | Disease-causing (★★) |
| CLCN5 G127V | 127 | Transmembrane | Disease-causing |
| CLCN5 G576E | 576 | Helical | Disease-causing |
Same protein, different disease
- Dent disease is also caused by CLCN5 variants; they fall mostly in different places as the X-linked recessive nephrolithiasis with renal failure variants (15 disease-causing).
- Hypophosphatemic rickets is also caused by CLCN5 variants; they fall mostly in different places as the X-linked recessive nephrolithiasis with renal failure variants (5 disease-causing).
- Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis is also caused by CLCN5 variants; they fall mostly in different places as the X-linked recessive nephrolithiasis with renal failure variants (5 disease-causing).
Diseases related to X-linked recessive nephrolithiasis with renal failure
- Dent disease, also linked to CLCN5
- Hypophosphatemic rickets, also linked to CLCN5
- Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis, also linked to CLCN5
Frequently asked questions
Which genes are linked to X-linked recessive nephrolithiasis with renal failure?
In CATVariant, X-linked recessive nephrolithiasis with renal failure is linked to 1 analyzed protein: CLCN5 (H(+)/Cl(-) exchange transporter 5).
How many genetic variants are linked to X-linked recessive nephrolithiasis with renal failure?
22 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.
Which uncertain variants in X-linked recessive nephrolithiasis with renal failure look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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