From protein uptake to Dent disease: An overview of the CLCN5 gene

Gene. 2020 Jul 15:747:144662. doi: 10.1016/j.gene.2020.144662. Epub 2020 Apr 11.

Abstract

Proteinuria is a well-known risk factor, not only for renal disorders, but also for several other problems such as cardiovascular diseases and overall mortality. In the kidney, the chloride channel Cl-/H+ exchanger ClC-5 encoded by the CLCN5 gene is actively involved in preventing protein loss. This action becomes evident in patients suffering from the rare proximal tubulopathy Dent disease because they carry a defective ClC-5 due to CLCN5 mutations. In fact, proteinuria is the distinctive clinical sign of Dent disease, and mainly involves the loss of low-molecular-weight proteins. The identification of CLCN5 disease-causing mutations has greatly improved our understanding of ClC-5 function and of the ClC-5-related physiological processes in the kidney. This review outlines current knowledge regarding the CLCN5 gene and its protein product, providing an update on ClC-5 function in tubular and glomerular cells, and focusing on its relationship with proteinuria and Dent disease.

Keywords: ClC-5; ClC-5 mutant proteins; Endocytosis; Kidney; Podocytes; Proximal tubular cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Chloride Channels / chemistry
  • Chloride Channels / genetics*
  • Chloride Channels / metabolism*
  • Dent Disease / genetics*
  • Dent Disease / pathology
  • Endocytosis*
  • Humans
  • Kidney / metabolism
  • Mutation / genetics
  • Phenotype

Substances

  • CLC-5 chloride channel
  • Chloride Channels