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Aliases for CLCN5 Gene

Aliases for CLCN5 Gene

  • Chloride Voltage-Gated Channel 5 2 3 5
  • Chloride Channel, Voltage-Sensitive 5 2 3
  • Chloride Transporter ClC-5 3 4
  • CLCK2 3 4
  • ClC-5 3 4
  • Voltage-Gated Chloride Ion Channel CLCN5 3
  • H(+)/Cl(-) Exchange Transporter 5 3
  • Nephrolithiasis 1 (X-Linked) 2
  • Nephrolithiasis 2, X-Linked 2
  • Chloride Channel Protein 5 4
  • Chloride Channel 5 2
  • Dent Disease 2
  • HCIC-K2 3
  • DENTS 3
  • NPHL1 3
  • NPHL2 3
  • CLC5 3
  • XLRH 3
  • XRN 3

External Ids for CLCN5 Gene

Previous HGNC Symbols for CLCN5 Gene

  • NPHL2
  • NPHL1

Previous GeneCards Identifiers for CLCN5 Gene

  • GC0XP048431
  • GC0XP047889
  • GC0XP048604
  • GC0XP048751
  • GC0XP049390
  • GC0XP049573
  • GC0XP049687
  • GC0XP047156

Summaries for CLCN5 Gene

Entrez Gene Summary for CLCN5 Gene

  • This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

GeneCards Summary for CLCN5 Gene

CLCN5 (Chloride Voltage-Gated Channel 5) is a Protein Coding gene. Diseases associated with CLCN5 include Dent Disease and Hypophosphatemic Rickets. Among its related pathways are Ion channel transport and Hepatic ABC Transporters. GO annotations related to this gene include ion channel activity and antiporter activity. An important paralog of this gene is CLCN3.

UniProtKB/Swiss-Prot for CLCN5 Gene

  • Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.

Gene Wiki entry for CLCN5 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCN5 Gene

Genomics for CLCN5 Gene

Regulatory Elements for CLCN5 Gene

Enhancers for CLCN5 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH0XF050078 0.6 ENCODE 18.6 +157.8 157751 4.4 ELF3 SOX13 CTCF PKNOX1 SAP130 ZNF384 ZBTB40 RAD21 RARA GATA3 CLCN5 GC0XP050030 PYY3
GH0XF049876 0.7 ENCODE 18.4 -44.0 -43978 3.5 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF48 YY1 GLIS2 CLCN5 PAGE4 USP27X-AS1
GH0XF050108 0.4 ENCODE 18.2 +185.6 185592 1.5 SOX5 SOX13 PKNOX1 HLF FOXA3 CEBPB TCF7 CREM CLCN5 PYY3 GC0XP050030
GH0XF050075 0.2 ENCODE 12.6 +153.3 153306 0.2 CTCF HDAC1 DMAP1 ZSCAN9 GATAD1 HOMEZ THAP11 GATAD2A RFX1 ZNF511 CLCN5 GC0XP050030 PYY3
GH0XF050107 0.6 ENCODE 12 +184.7 184666 0.1 CLCN5 PYY3 GC0XP050030
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around CLCN5 on UCSC Golden Path with GeneCards custom track

Promoters for CLCN5 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001031004 885 3400 TBP PKNOX1 ZNF133 ARID4B ZBTB40 YY1 GLIS2 ZNF263 KLF11 ZBTB2

Genomic Location for CLCN5 Gene

Chromosome:
X
Start:
49,922,615 bp from pter
End:
50,099,235 bp from pter
Size:
176,621 bases
Orientation:
Plus strand

Genomic View for CLCN5 Gene

Genes around CLCN5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCN5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCN5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCN5 Gene

Proteins for CLCN5 Gene

  • Protein details for CLCN5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51795-CLCN5_HUMAN
    Recommended name:
    H(+)/Cl(-) exchange transporter 5
    Protein Accession:
    P51795
    Secondary Accessions:
    • A1L475
    • B3KPN6
    • Q5JQD5
    • Q7RTN8

    Protein attributes for CLCN5 Gene

    Size:
    746 amino acids
    Molecular mass:
    83147 Da
    Quaternary structure:
    • Interacts with NEDD4 and NEDD4L.
    Miscellaneous:
    • The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels.

    Three dimensional structures from OCA and Proteopedia for CLCN5 Gene

    Alternative splice isoforms for CLCN5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLCN5 Gene

Post-translational modifications for CLCN5 Gene

  • Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation.
  • Ubiquitination at Lys 579
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CLCN5 Gene

Domains & Families for CLCN5 Gene

Gene Families for CLCN5 Gene

Suggested Antigen Peptide Sequences for CLCN5 Gene

Graphical View of Domain Structure for InterPro Entry

P51795

UniProtKB/Swiss-Prot:

CLCN5_HUMAN :
  • Contains 2 CBS domains.
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily.
Domain:
  • Contains 2 CBS domains.
Family:
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily.
genes like me logo Genes that share domains with CLCN5: view

Function for CLCN5 Gene

Molecular function for CLCN5 Gene

GENATLAS Biochemistry:
chloride voltage-gated channel 5,expressed in the epithelial cell lining the proximal tubules and the thick ascending limbs of Henles loop,likely involved in the receptor-mediated endocytic pathway
UniProtKB/Swiss-Prot Function:
Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.

Gene Ontology (GO) - Molecular Function for CLCN5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0005216 ion channel activity IEA --
GO:0005247 voltage-gated chloride channel activity IBA --
GO:0005254 chloride channel activity TAS 8559248
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with CLCN5: view
genes like me logo Genes that share phenotypes with CLCN5: view

Human Phenotype Ontology for CLCN5 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLCN5 Gene

MGI Knock Outs for CLCN5:

Animal Model Products

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CLCN5 Gene

Localization for CLCN5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCN5 Gene

Golgi apparatus membrane; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CLCN5 Gene COMPARTMENTS Subcellular localization image for CLCN5 gene
Compartment Confidence
endosome 5
lysosome 5
plasma membrane 5
vacuole 5
golgi apparatus 3
endoplasmic reticulum 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for CLCN5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005765 lysosomal membrane IDA 17897319
GO:0005768 endosome IEA,IBA --
GO:0005794 Golgi apparatus IEA --
GO:0005886 plasma membrane IEA --
genes like me logo Genes that share ontologies with CLCN5: view

Pathways & Interactions for CLCN5 Gene

genes like me logo Genes that share pathways with CLCN5: view

Gene Ontology (GO) - Biological Process for CLCN5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 8559248
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0007588 excretion TAS 8559248
GO:0034220 ion transmembrane transport TAS --
genes like me logo Genes that share ontologies with CLCN5: view

No data available for SIGNOR curated interactions for CLCN5 Gene

Drugs & Compounds for CLCN5 Gene

(2) Drugs for CLCN5 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for CLCN5 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6
genes like me logo Genes that share compounds with CLCN5: view

Transcripts for CLCN5 Gene

Unigene Clusters for CLCN5 Gene

Chloride channel, voltage-sensitive 5:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLCN5 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b
SP1: -
SP2: - -
SP3:

Relevant External Links for CLCN5 Gene

GeneLoc Exon Structure for
CLCN5
ECgene alternative splicing isoforms for
CLCN5

Expression for CLCN5 Gene

mRNA expression in normal human tissues for CLCN5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLCN5 Gene

This gene is overexpressed in Kidney - Cortex (x4.8).

Protein differential expression in normal tissues from HIPED for CLCN5 Gene

This gene is overexpressed in Fetal Brain (25.5) and Testis (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for CLCN5 Gene



Protein tissue co-expression partners for CLCN5 Gene

NURSA nuclear receptor signaling pathways regulating expression of CLCN5 Gene:

CLCN5

SOURCE GeneReport for Unigene cluster for CLCN5 Gene:

Hs.166486

mRNA Expression by UniProt/SwissProt for CLCN5 Gene:

P51795-CLCN5_HUMAN
Tissue specificity: Kidney. Moderately expressed in aortic vascular smooth muscle and endothelial cells, and at a slightly higher level in the coronary vascular smooth muscle.
genes like me logo Genes that share expression patterns with CLCN5: view

Primer Products

Orthologs for CLCN5 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CLCN5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLCN5 34 35
  • 97.3 (n)
cow
(Bos Taurus)
Mammalia CLCN5 34 35
  • 93.38 (n)
dog
(Canis familiaris)
Mammalia CLCN5 34 35
  • 93.38 (n)
rat
(Rattus norvegicus)
Mammalia Clcn5 34
  • 91.6 (n)
mouse
(Mus musculus)
Mammalia Clcn5 34 16 35
  • 91.34 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CLCN5 35
  • 90 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CLCN5 35
  • 76 (a)
OneToOne
chicken
(Gallus gallus)
Aves CLCN5 34 35
  • 79.03 (n)
lizard
(Anolis carolinensis)
Reptilia CLCN5 35
  • 83 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia clcn5 34
  • 73.03 (n)
Str.16383 34
African clawed frog
(Xenopus laevis)
Amphibia LOC397880 34
zebrafish
(Danio rerio)
Actinopterygii CLCN5 (1 of 2) 35
  • 79 (a)
OneToMany
clcn5 35
  • 76 (a)
OneToMany
si:dkey-22f5.8 34
  • 72.81 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG5284 36
  • 59 (a)
ClC-c 35
  • 54 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea clh-5 35
  • 50 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GEF1 35
  • 31 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 58 (a)
OneToMany
Species where no ortholog for CLCN5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CLCN5 Gene

ENSEMBL:
Gene Tree for CLCN5 (if available)
TreeFam:
Gene Tree for CLCN5 (if available)

Paralogs for CLCN5 Gene

Paralogs for CLCN5 Gene

(2) SIMAP similar genes for CLCN5 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with CLCN5: view

Variants for CLCN5 Gene

Sequence variations from dbSNP and Humsavar for CLCN5 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
rs144207967 Nephrolithiasis 2 (NPHL2) [MIM:300009] 50,090,706(+) TAGCA(C/G)TTCCA reference, missense
rs151340622 Nephrolithiasis 2 (NPHL2) [MIM:300009], Pathogenic 50,081,723(+) GGTGC(G/T)GGCAG reference, missense
rs151340623 Nephrolithiasis 2 (NPHL2) [MIM:300009], Pathogenic 50,090,139(+) CTGTT(C/T)CTCTT reference, missense
rs151340625 Nephrolithiasis 1 (NPHL1) [MIM:310468], Pathogenic 50,088,867(+) GGTTG(A/G)GGCTG reference, missense
rs151340626 Hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554], Pathogenic 50,085,987(+) CTTGT(C/T)GGCTG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for CLCN5 Gene

Variant ID Type Subtype PubMed ID
dgv4238n106 CNV duplication 24896259
esv2673611 CNV deletion 23128226
esv33289 CNV loss 17666407
esv3337634 CNV duplication 20981092
esv3573959 CNV loss 25503493
esv3573960 CNV loss 25503493
esv3576875 CNV gain 25503493
nsv1077585 CNV duplication 25765185
nsv1077586 CNV duplication 25765185
nsv1132764 CNV duplication 24896259
nsv1147061 CNV duplication 26484159
nsv1151696 CNV duplication 26484159
nsv508770 CNV insertion 20534489

Variation tolerance for CLCN5 Gene

Residual Variation Intolerance Score: 22.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.81; 34.02% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CLCN5 Gene

Human Gene Mutation Database (HGMD)
CLCN5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLCN5

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLCN5 Gene

Disorders for CLCN5 Gene

MalaCards: The human disease database

(17) MalaCards diseases for CLCN5 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
dent disease
  • dent disease 2
hypophosphatemic rickets
  • hypophosphatemic rickets disorders
proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis
  • low molecular weight proteinuria with hypercalciuria and nephrocalcinosis
nephrolithiasis, type i
  • nephrolithiasis type i
nephrolithiasis
  • calculus of kidney and ureter
- elite association - COSMIC cancer census association via MalaCards
Search CLCN5 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CLCN5_HUMAN
  • Hypophosphatemic rickets, X-linked recessive (XLRHR) [MIM:300554]: A renal disease belonging to the Dent disease complex, a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only. {ECO:0000269 PubMed:8559248}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990]: An X-linked renal disease belonging to the Dent disease complex, a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. LMWPHN is a slowly progressive disorder. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure. {ECO:0000269 PubMed:11136179, ECO:0000269 PubMed:9062355}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Nephrolithiasis 1 (NPHL1) [MIM:310468]: An X-linked recessive renal disease belonging to the Dent disease complex, a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia. {ECO:0000269 PubMed:8559248}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Nephrolithiasis 2 (NPHL2) [MIM:300009]: An X-linked recessive renal disease belonging to the Dent disease complex, a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Nephrolithiasis type 2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia. {ECO:0000269 PubMed:15086899, ECO:0000269 PubMed:16247550, ECO:0000269 PubMed:16416111, ECO:0000269 PubMed:16822791, ECO:0000269 PubMed:17262170, ECO:0000269 PubMed:18025833, ECO:0000269 PubMed:19657328, ECO:0000269 PubMed:8559248, ECO:0000269 PubMed:9187673, ECO:0000269 PubMed:9259268, ECO:0000269 PubMed:9602200, ECO:0000269 PubMed:9853249}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CLCN5

Genetic Association Database (GAD)
CLCN5
Human Genome Epidemiology (HuGE) Navigator
CLCN5
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CLCN5
genes like me logo Genes that share disorders with CLCN5: view

No data available for Genatlas for CLCN5 Gene

Publications for CLCN5 Gene

  1. X-linked recessive nephrolithiasis: presentation and diagnosis in children. (PMID: 9602200) Schurman S.J. … Scheinman S.J. (J. Pediatr. 1998) 2 3 4 22 64
  2. Idiopathic low molecular weight proteinuria associated with hypercalciuric nephrocalcinosis in Japanese children is due to mutations of the renal chloride channel (CLCN5). (PMID: 9062355) Lloyd S.E. … Thakker R.V. (J. Clin. Invest. 1997) 3 4 22 46 64
  3. A common molecular basis for three inherited kidney stone diseases. (PMID: 8559248) Lloyd S.E. … Thakker R.V. (Nature 1996) 2 3 4 22 64
  4. Novel CLCN5 mutations in patients with Dent's disease result in altered ion currents or impaired exchanger processing. (PMID: 19657328) Grand T. … Lourdel S. (Kidney Int. 2009) 3 4 22 64
  5. Nucleotide recognition by the cytoplasmic domain of the human chloride transporter ClC-5. (PMID: 17195847) Meyer S. … Dutzler R. (Nat. Struct. Mol. Biol. 2007) 3 4 22 64

Products for CLCN5 Gene

Sources for CLCN5 Gene

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