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GENATLAS PHENOTYPE
last update : 06-10-2021
Symbol NPHL2
Location Xp11.23
Name nephrolithiasis 2
Other name(s)
  • vitamin D-resistant rickets, X-linked
  • hypophosphatemic vitamin D-resistant rickets
  • Dent's syndrome
    • Corresponding gene CLCN5
    Other symbol(s) XLRH, HPDR, XLH, HYP
    Main clinical features
  • proximal renal tubular syndrome characterized by : low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets and progressive renal failure
  • cases with Bartter syndrome phenotype seen in Dent disease patients that may represent a distinct form of Bartter syndrome; growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency (PMID: 20680351))
    • Genetic determination sex linked
    Related entries . including Japanese variant
    Function/system disorder metabolism/membrane transport
    Type disease
    Gene product
    Name chloride voltage gated channel 5 (CLCN5)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    missense   abnormal protein/loss of function 85 mutations identified so far
    Remark(s)
  • missense mutation W547G was shown to alter the premRNA
    • splicing pattern
  • Alu insertion led to an aberrant splicing of the CLCN5 pre-mRNA that skipped exon 11, by interfering with splicing regulatory elements (would predict a truncated ClC-5 protein that lacks critical domains for sorting and chloride channel function)
  • mutation in CLCN5 gene, c.1073G>A associated to Barrter-like phenotype (PMID: 20680351))
  • CLCN5:R345W variant exhibited slightly higher Cl-/H+ transport than ClC-5:S244L, but co-localized with early endosomes, suggesting decreased CLCN5:R345W membrane trafficking is perhaps in a fully functional form (PMID: 31852738))