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FLASH GENE
Symbol CLCN2 contributors: mct/npt - updated : 18-12-2016
HGNC name chloride channel 2
HGNC id 2020
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