Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CLCN5 contributors: mct - updated : 03-09-2012
HGNC name chloride channel 5 (nephrolithiasis 2, X-linked, Dent disease)
HGNC id 2023
Corresponding disease
FILWP familial idiopathic low molecular weight proteinuria
NPHL1 nephrolithiasis, recessive, with renal failure
NPHL2 nephrolithiasis 2
Location Xp11.23      Physical location : 49.687.224 - 49.863.892
Synonym name chloride channel protein 5
Synonym symbol(s) CLC5, XRN, XLRH, CLCK2, CLC5, hCIC-K2, hClC-K2, DENTS
DNA
TYPE functioning gene
STRUCTURE 176.67 kb     18 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure AP1-like element and CAMP responsive element
MAPPING cloned Y linked   status confirmed
Physical map
VDAC1LP Xp11.2 voltage-dependent anion channel 1-like pseudogene LOC139163 Xp11.23 similar to Sal-like protein 1 (Zinc finger protein SALL1) (Spalt-like transcription factor 1) (HSal1) GAGEB1 Xp11.23 G antigen, family B, 1 (prostate associated) GAGEC1 Xp11.23 G antigen, family C, 1 LOC389856 X similar to ubiquitin specific protease 27, X chromosome CLCN5 Xp11.22 chloride channel 5 (nephrolithiasis 2, X-linked, Dent disease) AKAP4 Xp11.2 a kinase (PRKA) anchor protein 4 CCNB3 Xp11 cyclin B3 LOC139189 Xp11.23 similar to Diacylglycerol kinase, delta (Diglyceride kinase) (DGK-delta) (DAG kinase delta) (130 kDa diacylglycerol kinase)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
18 - 10108 - 816 - 2005 16034421
18 - 9849 - 816 - 2005 16034421
- - 9505 - 746 - 2005 16034421
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
urinarykidneyHenle's loopascending thick limb  
Urinarykidneytubuleconvoluted tubuleproximal tubule  Homo sapiens
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 within its intracellular carboxy-terminus, implicated in intracellular targetting and trafficking as well as protein-protein interactions
  • C terminal internalization motif resembling the PY motif
  • HOMOLOGY
    interspecies ortholog to rattus clcn5
    ortholog to murine Clcn5
    Homologene
    FAMILY CLC family of voltage-gated chloride channels
    CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    text
  • expressed in endosomes and apical membranes of renal tubules
  • basic FUNCTION
  • chloride voltage-gated channel, likely involved in the receptor-mediated endocytic pathway
  • functioning as electrogenic Cl-/H+ exchanger, carrying a substantial amount of protons across the plasma membrane when activated by positive voltages
  • playing a role in the activation of apical protein endocytosis in kidney proximal tubules by regulating trafficking of megalin and cubilin at the brush border
  • electrically shunting Cl- channel in early endosomes, facilitating intraluminal acidification
  • may compensate the charge accumulation by endosomal proton pumps
  • playing a definitive role in the trafficking and acidification-dependent recycling of apical membrane proteins
  • regulates dentin development through TGFB1 pathway
  • interaction with KIF3B is important for CLCN5 plasma membrane expression and for facilitating endocytosis and microtubular transport in the kidney
  • endosomal chloride concentration, which is raised by CLCN5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis
  • essential for the endocytic activity of the proximal tubule cells and the tubular clearance of proteins filtered in the glomeruli
  • role of CFTR and CLCN5 in modulating vacuolar H+-ATPase activity in kidney proximal tubule
  • Cl-/H+ antiporters that carry out fundamental physiological tasks by transporting Cl- across plasma membrane and intracellular compartments
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with kinesin family member 3B (KIF3B), a heterotrimeric motor protein that facilitates fast anterograde translocation of membranous organelles
  • HNF1A directly regulates the expression of CLCN5 in the renal proximal tubule and yield insights into the mechanisms governing epithelial differentiation and specialized transport activities in the kidney
  • cell & other
    REGULATION
    activated by positive voltages
    ASSOCIATED DISORDERS
    corresponding disease(s) NPHL1 , NPHL2 , FILWP
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    CIC-( CL- mouse model for Dent's syndrome (NPHL2)