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FLASH GENE
Symbol CLCN7 contributors: mct - updated : 20-06-2019
HGNC name chloride channel 7
HGNC id 2025
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
two CBS forming a stable globular domain
secondary structure twelve alpha helical membrane spanning domains
mono polymer heteromer , complex
HOMOLOGY
interspecies ortholog to murine Clcn7
ortholog to rattus clcn7
Homologene
FAMILY chloride channel family
CATEGORY transport channel
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm,organelle,membrane
intracellular,cytoplasm,organelle,endoplasmic reticulum
intracellular,cytoplasm,organelle,endosome
intracellular,cytoplasm,organelle,lysosome
intracellular,cytoplasm,cytosolic,vesicle
text
  • co-localized with OSTM1 in late endosomal/lysosomal Cl(-) channel, inserted in the ruffled border of bone-resorbing osteoclasts, by exocytic fusion with the H(+)-ATPase
  • is synthesized by microglia but it is mistargeted and appears to be degraded by an endoplasmic reticulum-associated degradation pathway
  • located in late endosomes and lysosomes
    • basic FUNCTION
  • chloride voltage-gated channel, providing the chloride conductance requested for an efficient proton pumping by the H+-ATPase of the osteoclast ruffled membrane
  • chloride channel of late endosomes and lysosomes, playing a pivotal role in acidifying the extracellular lysosomal membrane between osteoclast and bone
  • voltage-gated chloride channel involved in the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport
  • Cl-/H+ antiporter, that it constitutes the major Cl- permeability of lysosomes, and that it is important in lysosomal acidification
  • CLCN7 functions as an antiporter
  • implied in the pathogenesis of lysosomal storage disease and osteopetrosis
  • CLCN7 associates with another protein, OSTM1, which plays an important role in its correct lysosomal targeting
  • is essential for osteoclasts to resorb craniofacial bones to enable tooth eruption and root development
  • CLCN7 may affect tooth development by directly targeting tooth cells, and regulate tooth eruption through dental follicle cells (DFCs) mediated osteoclast pathway
  • regulates the pattern and early development of craniofacial bone and tooth
  • critical role of the CLCN7 chloride/proton antiporter in maintaining lysosomal pH within a very narrow range
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forming a molecular complex with OSTM1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • H+ ATPase
  • interacting with MITF (MITF regulation of the cathepsin K, CLCN7, and OSTM1 genes, which are critical for osteoclast resorption, suggesting that MITF may be a master regulator of osteoclast function and bone resorption)
  • interacting with OSTM1 (OSTM1 transmembrane domain suffices for its CLCN7-dependent trafficking to lysosomes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) OPTB4 , OPTA2 , CADDLS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    in lysosomal storage disease and neurodegeneration
    constitutional     --over  
    expression of both CLCN7 and OSTM1 is increased in activated microglia, which can account for the increased delivery of CLCN7 to lysosomes
    constitutional       loss of function
    reduces bone and dentin mineral density but does not affect enamel mineralization
    Susceptibility to variability of bone mineral density (BMD)in postmenopausal women
    Variant & Polymorphism other significant association of CLCN7 polymorphisms with the variance of BMD and bone resorption marker levels in postmenopausal women
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Clcn7- mice developping severe osteopetrosis
  • mice lacking Clc-7 show altered lysosomal function that leads to severe lysosomal storage