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FLASH GENE
Symbol CLCN5 contributors: mct - updated : 03-09-2012
HGNC name chloride channel 5 (nephrolithiasis 2, X-linked, Dent disease)
HGNC id 2023
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • twelve alpha helical membrane spanning protein cytoplasmic N and C terminals
  • two CBS forming a stable globular domain within its intracellular carboxy-terminus, implicated in intracellular targetting and trafficking as well as protein-protein interactions
  • C terminal internalization motif resembling the PY motif
  • HOMOLOGY
    interspecies ortholog to rattus clcn5
    ortholog to murine Clcn5
    Homologene
    FAMILY CLC family of voltage-gated chloride channels
    CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    text
  • expressed in endosomes and apical membranes of renal tubules
  • basic FUNCTION
  • chloride voltage-gated channel, likely involved in the receptor-mediated endocytic pathway
  • functioning as electrogenic Cl-/H+ exchanger, carrying a substantial amount of protons across the plasma membrane when activated by positive voltages
  • playing a role in the activation of apical protein endocytosis in kidney proximal tubules by regulating trafficking of megalin and cubilin at the brush border
  • electrically shunting Cl- channel in early endosomes, facilitating intraluminal acidification
  • may compensate the charge accumulation by endosomal proton pumps
  • playing a definitive role in the trafficking and acidification-dependent recycling of apical membrane proteins
  • regulates dentin development through TGFB1 pathway
  • interaction with KIF3B is important for CLCN5 plasma membrane expression and for facilitating endocytosis and microtubular transport in the kidney
  • endosomal chloride concentration, which is raised by CLCN5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis
  • essential for the endocytic activity of the proximal tubule cells and the tubular clearance of proteins filtered in the glomeruli
  • role of CFTR and CLCN5 in modulating vacuolar H+-ATPase activity in kidney proximal tubule
  • Cl-/H+ antiporters that carry out fundamental physiological tasks by transporting Cl- across plasma membrane and intracellular compartments
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with kinesin family member 3B (KIF3B), a heterotrimeric motor protein that facilitates fast anterograde translocation of membranous organelles
  • HNF1A directly regulates the expression of CLCN5 in the renal proximal tubule and yield insights into the mechanisms governing epithelial differentiation and specialized transport activities in the kidney
  • cell & other
    REGULATION
    activated by positive voltages
    ASSOCIATED DISORDERS
    corresponding disease(s) NPHL1 , NPHL2 , FILWP , HYP2
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    CIC-( CL- mouse model for Dent's syndrome (NPHL2)