Hypophosphatemic rickets: genes and variants
Hypophosphatemic rickets is linked to 1 analyzed protein (CLCN5). 5 DNA variants are known to cause it; 29 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: hypophosphatemic rickets, X-linked recessive
Genes linked to Hypophosphatemic rickets
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.
5 disease-causing and 28 uncertain variants in CLCN5 are linked to Hypophosphatemic rickets.
Weakly linked (only a few uncertain records): HRAS.
Known disease-causing variants in Hypophosphatemic rickets
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CLCN5 S314L | 314 | Helical | Disease-causing (★★) |
| CLCN5 C291R | 291 | Transmembrane | Disease-causing (★★) |
| CLCN5 G532D | 532 | Transmembrane | Disease-causing (★) |
| CLCN5 G576R | 576 | Helical | Disease-causing (★) |
| CLCN5 G600V | 600 | Note=Loop between two helices | Disease-causing (★) |
Same protein, different disease
- Dent disease is also caused by CLCN5 variants; they fall mostly in different places as the Hypophosphatemic rickets variants (15 disease-causing).
Diseases related to Hypophosphatemic rickets
- Dent disease, also linked to CLCN5
- Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis, also linked to CLCN5
- X-linked recessive nephrolithiasis with renal failure, also linked to CLCN5
Frequently asked questions
Which genes are linked to Hypophosphatemic rickets?
In CATVariant, Hypophosphatemic rickets is linked to 1 analyzed protein: CLCN5 (H(+)/Cl(-) exchange transporter 5).
How many genetic variants are linked to Hypophosphatemic rickets?
43 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 29 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hypophosphatemic rickets 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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