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FLASH GENE
Symbol CLCN7 contributors: mct - updated : 20-06-2019
HGNC name chloride channel 7
HGNC id 2025
Corresponding disease
CADDLS Cutaneous Albinism, Developmental Delay, and Lysosomal Storage
OPTA2 osteopetrosis, type II
OPTB4 osteopetrosis, Albers-Schonberg disease 4
Location 16p13.3      Physical location : 1.494.934 - 1.525.085
Synonym name
  • chloride channel protein 7
  • protein phosphatase 1, regulatory subunit 63
  • H(+)/Cl(-) exchange transporter 7
  • Synonym symbol(s) CLC7, CLC-7, OPTA2, FLJ26686, FLJ39644, FLJ46423, OPTB4, PPP1R63
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 30.15 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • two MITF-binding sites (M-boxes) in the promoter
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 4153 - 781 - 1999 10500249
    25 - 4225 - 805 - 1999 10500249
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     stomach     Homo sapiens
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Nervousplexus choroid     Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone   
    Muscular    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoclast
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    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
  • 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