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FLASH GENE
Symbol CLCN2 contributors: mct/npt - updated : 18-12-2016
HGNC name chloride channel 2
HGNC id 2020
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
24 - 3299 98.4 898 - 2006 16469788
23 - 3167 - 854 - 2006 16469788
24 - 3248 - 881 - 2006 16469788
23 - 3212 - 869 - 2006 16469788
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Visualeyeretina   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialsensoryvisualouter nuclear layer 
Epithelialsensoryvisualinner nuclear layer 
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • twelve alpha helical membrane spanning protein cytoplasmic N and C terminals
  • two CBS forming a stable globular domain
  • N- and C-terminal regions with regulatory functions and a transmembrane region which forms the ring of the pore
  • HOMOLOGY
    interspecies ortholog to murine Clcn2
    homolog to Drosophila Cg6942
    homolog to C.elegans E04f6.11 and Clh-3
    Homologene
    FAMILY
  • chloride channel family
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    text in the plasma membrane of rod bipolar cell bodies (Hohberger 2009)
    basic FUNCTION
  • chloride voltage-gated channel, playing a role in the regulation of cell volume,membrane potential stabilization, signal transduction and trans-epithelial transport
  • could be implicated in epilepsy, even in the absence of mutations
  • mediates an inwardly rectified chloride conductance activated by cell swelling, low extracellular pH or membrane hyperpolarization
  • may play an important role in the regulation of cardiac pacemaker activity, which may become more prominent under stressed or pathological conditions
  • is involved in brain ion and water homoeostasis
  • is important in maintaining the volume of trabecular meshwork cells by adjusting the outflow of aqueous solutions and maintaining the fluid balance
  • functional relationship between MLC1 and CLCN2, which is probably mediated by HEPACAM, suggesting that CLCN2 participates in the pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text
  • small molecule transport
  • ion transport
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CRBN (a distal region of the C-terminus interacts with the Lon domain of CRBN)
  • HEPACAM targets CLCN2 to cell junctions, increases CLCN2 mediated currents, and changes its functional properties
  • JAK2 down-regulates CLCN2 activity and thus counteracts Cl(-) exit, an effect which may impact on cell volume regulation
  • CLCN2 is unnecessary for MLC1 and HEPACAM localization in brain, whereas HEPACAM is important for targeting MLC1 and ClCN2 to specialized glial domains
  • HEPACAM works as an auxiliary subunit of the chloride channel CLCN2, regulating its targeting to cell-cell junctions and modifying its functional properties
  • basolateral sorting of CLCN2 is mediated by interactions between a dileucine motif and the clathrin adaptor AP1B1
  • HEPACAM binds to itself, to MLC1 and to CLCN2, and directs these proteins to cell-cell contacts
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EGMA , ECA3 , JAE , LKPAT
    Susceptibility to idiopathic generalized epilepsy (Kleefuss-Lie 2009)
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualanterior chamber
    may be a promising and potential novel therapeutic strategy for combating primary open‑angle glaucoma
    ANIMAL & CELL MODELS
  • ClCN2 deficient mice suffer from degeneration of male germ cells in testis and photoreceptors in the retina (Hohberger 2009)
  • white matter of the brain and spinal cord of ClC-2 knock-out mice developed widespread vacuolation that progressed with age (Blanz 2007)
  • increase in the amiloride-sensitive short-circuit current in Clcn2(-/-) mice revealed a compensatory mechanism that is activated in the colons of mice that lack the ClC-2 channel