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FLASH GENE
Symbol CLCN7 contributors: mct - updated : 21-02-2012
HGNC name chloride channel 7
HGNC id 2025
Corresponding disease
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
    Physical map
    FLJ32252 16p13.3 hypothetical protein FLJ32252 SSTR5 16p13.3 somatostatin receptor 5 LOC390663 16 similar to Williams-Beuren syndrome critical region protein 25 LOC390664 16 similar to C1q Related CACNA1H 16p13.3 calcium channel, voltage-dependent, alpha 1H subunit TPS1 16p13.3 tryptase, alpha TPSB2 16p13.3 tryptase beta 2 TPSG1 16p13.3 tryptase gamma 1 TPSB1 16p13.3 tryptase beta 1 TPSD1 16p13.3 tryptase delta 1 ISP2 16p13.3 implantation serine proteinase 2 LOC123788 16p13.3 similar to mast cell protease-11 UBE2I 16p13.3 ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast) BAIAP3 16p13.3 BAI1-associated protein 3 LOC388200 16 LOC388200 CAB56184 FLJ23360 16p13.3 hypothetical protein FLJ23360 UNKL 16p13.3 unkempt-like (Drosophila) LOC283951 16p13.3 hypothetical protein LOC283951 LOC388201 16 LOC388201 LOC388202 16 similar to KIAA0445 protein CLCN7 16p13.3 chloride channel 7 LOC390666 16 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 LOC390667 16 similar to Neuronal pentraxin II precursor (NP-II) (NP2) KIAA0683 16p13.3 similar to Neuronal pentraxin II precursor (NP-II) (NP2) KIAA0590 16p13.3 similar to Neuronal pentraxin II precursor (NP-II) (NP2) FLJ20898 16p13.3 hypothetical protein FLJ20898 CRAMP1L 16p13.3 Crm, cramped-like (Drosophila) C16orf34 16p13.3 chromosome 16 open reading frame 34 MAPK8IP3 16p13.3 mitogen-activated protein kinase 8 interacting protein 3 NME3 16q13 non-metastatic cells 3, protein expressed in MRPS34 16p13.3 mitochondrial ribosomal protein S34 LOC390668 16 similar to hypothetical protein 6820428D13 SSB3 16p13.3 SPRY domain-containing SOCS box protein SSB-3 NUBP2 16p13.3 nucleotide binding protein 2 (MinD homolog, E. coli) IGFALS 16p13.3 insulin-like growth factor binding protein, acid labile subunit HAGH 16p13.3 hydroxyacyl glutathione hydrolase
    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
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Nervousbrain    
    Reproductivemale systemtestis   
    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
  • 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
  • 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
    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
    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
    Clcm7- mice developping severe osteopetrosis