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FLASH GENE
Symbol CLCN2 contributors: mct/npt - updated : 18-12-2016
HGNC name chloride channel 2
HGNC id 2020
Corresponding disease
ECA3 epilepsy, childhood absence, 3
EGMA epilepsy with grand mal seizures on awakening
JAE epilepsy, juvenile absence
LKPAT leukoencephalopathy with ataxia
Location 3q27.1      Physical location : 184.063.976 - 184.079.391
Synonym name epilepsy, idiopathic generalized, susceptibility to
Synonym symbol(s) CLC2, CIC-2, ECA3, EGI3, EGMA
DNA
TYPE functioning gene
STRUCTURE 15.47 kb     24 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
FLJ12748 3q27.3 hypothetical protein FLJ12748 PSARL 3q27.3 presenilin associated, rhomboid-like LOC391598 3 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) LOC391599 3 similar to cytochrome P450 2P1 ABCC5 3q27 ATP-binding cassette, sub-family C (CFTR/MRP), member 5 LOC389179 3 similar to Elongation factor 1-alpha 1 (EF-1-alpha-1) (Elongation factor 1 A-1) (eEF1A-1) (Elongation factor Tu) (EF-Tu) HTR3D 3q27.3 5-hydroxytryptamine receptor 3 subunit D HTR3C 3q27.3 5-hydroxytryptamine receptor 3 subunit C LOC389180 3 similar to 5-hydroxytryptamine receptor 3 subunit C HTR3E 3q27.3 5-hydroxytryptamine serotonin receptor 3E LOC285244 3q27.3 similar to Heat shock protein HSP 90-alpha (HSP 86) EIF2B5 3q27 eukaryotic translation initiation factor 2B, subunit 5 epsilon, 82kDa DVL3 3q27 dishevelled, dsh homolog 3 (Drosophila) LOC389181 3 hypothetical gene supported by U14990; U14992; NM_001005 AP2M1 3q28 adaptor-related protein complex 2, mu 1 subunit ABCF3 3q25-q25.2 ATP-binding cassette, sub-family F (GCN20), member 3 LOC90113 3q27.3 hypothetical protein BC009862 ALG3 3q27.3 asparagine-linked glycosylation 3 homolog (yeast, alpha-1,3-mannosyltransferase) MGC2408 3q27.3 hypothetical protein MGC2408 CAM-KIIN 3q27.3 CaM-KII inhibitory protein ECE2 3q27q28 endothelin converting enzyme 2 PSMD2 3q27.3 proteasome (prosome, macropain) 26S subunit, non-ATPase, 2 EIF4G1 3q27-qter eukaryotic translation initiation factor 4 gamma, 1 MGC21688 3q27.3 hypothetical protein MGC21688 CLCN2 3q27-q28 chloride channel 2 POLR2H 3q28 polymerase (RNA) II (DNA directed) polypeptide H THPO 3q27-q28 thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor) CHRD 3q27 chordin LOC285248 3q27.3 hypothetical LOC285248 LOC391600 3 similar to RIKEN cDNA 2310042E22 EPHB3 3q21-qter EphB3 MAGEF1 3q13 EphB3 LOC389182 3 LOC389182
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