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Aliases for CLCN3 Gene

Aliases for CLCN3 Gene

  • Chloride Voltage-Gated Channel 3 2 3 5
  • Chloride Channel, Voltage-Sensitive 3 2 3
  • Chloride Channel Protein 3 3 4
  • Chloride Transporter ClC-3 3 4
  • Chloride Channel 3 2 3
  • ClC-3 3 4
  • H(+)/Cl(-) Exchange Transporter 3 3
  • CLC3 3

External Ids for CLCN3 Gene

Previous GeneCards Identifiers for CLCN3 Gene

  • GC04P171346
  • GC04P170970
  • GC04P171126
  • GC04P171237
  • GC04P170916
  • GC04P170778
  • GC04P170541
  • GC04P166296

Summaries for CLCN3 Gene

Entrez Gene Summary for CLCN3 Gene

  • This gene encodes a member of the voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

GeneCards Summary for CLCN3 Gene

CLCN3 (Chloride Voltage-Gated Channel 3) is a Protein Coding gene. Diseases associated with CLCN3 include Cystic Fibrosis. Among its related pathways are Activation of cAMP-Dependent PKA and Ion channel transport. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and ion channel activity. An important paralog of this gene is CLCN5.

UniProtKB/Swiss-Prot for CLCN3 Gene

  • Mediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.

Gene Wiki entry for CLCN3 Gene

Additional gene information for CLCN3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCN3 Gene

Genomics for CLCN3 Gene

GeneHancer (GH) Regulatory Elements for CLCN3 Gene

Promoters and enhancers for CLCN3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04I169618 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 551.6 +8.4 8416 4.2 HDGF PKNOX1 FOXA2 SMAD1 MLX ARNT ARID4B SIN3A DMAP1 ZNF2 CLCN3 NEK1 GC04M169663
GH04I169610 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 550.8 -0.6 -648 3.7 HDGF PKNOX1 CLOCK SMAD1 ARNT ZFP64 ARID4B SIN3A FEZF1 DMAP1 NEK1 CLCN3 LOC105377529
GH04I169656 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE 569.6 +48.2 48195 8.3 HDGF PKNOX1 SMAD1 ARNT ARID4B NEUROD1 SIN3A ZNF2 YY1 POLR2B CLCN3 NEK1 GC04M169663
GH04I169649 Enhancer 1 Ensembl ENCODE 12.2 +37.7 37687 1 HDAC1 FOXA2 TAF9B ARNT YY1 CHAMP1 TCF12 RXRA ZBTB2 CEBPB NEK1 CLCN3 SH3RF1 GC04M169663
GH04I169604 Enhancer 1.2 Ensembl ENCODE dbSUPER 7.5 -7.7 -7725 1.2 HDAC1 ATF1 TAF9B ARNT ZBTB40 TCF12 RCOR1 FOS ATF7 RUNX3 NEK1 MFAP3L CLCN3 LOC105377529
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CLCN3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLCN3 gene promoter:

Genomic Locations for CLCN3 Gene

Genomic Locations for CLCN3 Gene
chr4:169,612,633-169,723,673
(GRCh38/hg38)
Size:
111,041 bases
Orientation:
Plus strand
chr4:170,533,784-170,644,824
(GRCh37/hg19)

Genomic View for CLCN3 Gene

Genes around CLCN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCN3 Gene

Proteins for CLCN3 Gene

  • Protein details for CLCN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51790-CLCN3_HUMAN
    Recommended name:
    H(+)/Cl(-) exchange transporter 3
    Protein Accession:
    P51790
    Secondary Accessions:
    • B7Z932
    • B9EGJ9
    • D3DP34
    • E9PB97
    • O14918
    • Q86Z21

    Protein attributes for CLCN3 Gene

    Size:
    818 amino acids
    Molecular mass:
    90966 Da
    Quaternary structure:
    • Homo- or heterodimer. Isoform 2 interacts with GOPC, PDZK1 and SLC9A3R1/EBP50.
    Miscellaneous:
    • The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).
    SequenceCaution:
    • Sequence=BAC54560.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA55281.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for CLCN3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLCN3 Gene

Post-translational modifications for CLCN3 Gene

No data available for DME Specific Peptides for CLCN3 Gene

Domains & Families for CLCN3 Gene

Gene Families for CLCN3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for CLCN3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P51790

UniProtKB/Swiss-Prot:

CLCN3_HUMAN :
  • Isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC.
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
Domain:
  • Isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC.
Family:
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
genes like me logo Genes that share domains with CLCN3: view

Function for CLCN3 Gene

Molecular function for CLCN3 Gene

GENATLAS Biochemistry:
chloride voltage-gated channel 3,expressed in tissues derived from neuroectoderm
UniProtKB/Swiss-Prot Function:
Mediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.

Phenotypes From GWAS Catalog for CLCN3 Gene

Gene Ontology (GO) - Molecular Function for CLCN3 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,IEA --
GO:0005254 chloride channel activity IDA,TAS 12471024
GO:0005515 protein binding IPI 12471024
genes like me logo Genes that share ontologies with CLCN3: view
genes like me logo Genes that share phenotypes with CLCN3: view

Animal Models for CLCN3 Gene

MGI Knock Outs for CLCN3:

Animal Model Products

CRISPR Products

miRNA for CLCN3 Gene

miRTarBase miRNAs that target CLCN3

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CLCN3 Gene

Localization for CLCN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCN3 Gene

Isoform 1: Early endosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Cytoplasmic vesicle, secretory vesicle membrane; Multi-pass membrane protein. Note=Isoform 1 is localized mainly in late endosomes. {ECO:0000269 PubMed:12471024}.
Isoform 2: Golgi apparatus membrane; Multi-pass membrane protein. Note=Isoform 2 is mainly enriched in the Golgi. {ECO:0000269 PubMed:12471024}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CLCN3 gene
Compartment Confidence
plasma membrane 5
golgi apparatus 5
endosome 5
extracellular 2
cytosol 2
lysosome 2
mitochondrion 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CLCN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IDA 12471024
GO:0005770 late endosome IDA 12471024
GO:0005794 Golgi apparatus IEA,IDA 12471024
genes like me logo Genes that share ontologies with CLCN3: view

Pathways & Interactions for CLCN3 Gene

genes like me logo Genes that share pathways with CLCN3: view

Pathways by source for CLCN3 Gene

Gene Ontology (GO) - Biological Process for CLCN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS,IEA 7665160
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0006885 regulation of pH TAS 12471024
GO:0034220 ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with CLCN3: view

No data available for SIGNOR curated interactions for CLCN3 Gene

Drugs & Compounds for CLCN3 Gene

(8) Drugs for CLCN3 Gene - From: ApexBio, DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phloretin Pharma Inhibitor A dihydrochalcone found in apple 0
9-AC Pharma 0
DCPIB Pharma 0
GaTx2 Pharma Channel blocker 0
NPPB Pharma Channel blocker inhibitor of chloride channel 0

(4) Additional Compounds for CLCN3 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6

(4) ApexBio Compounds for CLCN3 Gene

Compound Action Cas Number
9-AC 723-62-6
DCPIB 82749-70-0
GaTx2 194665-85-5
NPPB inhibitor of chloride channel 107254-86-4
genes like me logo Genes that share compounds with CLCN3: view

Drug Products

Transcripts for CLCN3 Gene

Unigene Clusters for CLCN3 Gene

Chloride channel, voltage-sensitive 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLCN3 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b
SP1: - - - -
SP2: - - - - -
SP3: -
SP4:
SP5:
SP6:
SP7:

Relevant External Links for CLCN3 Gene

GeneLoc Exon Structure for
CLCN3
ECgene alternative splicing isoforms for
CLCN3

Expression for CLCN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLCN3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CLCN3 Gene

This gene is overexpressed in Cervix (43.6) and Breast (9.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CLCN3 Gene



Protein tissue co-expression partners for CLCN3 Gene

NURSA nuclear receptor signaling pathways regulating expression of CLCN3 Gene:

CLCN3

SOURCE GeneReport for Unigene cluster for CLCN3 Gene:

Hs.481186

mRNA Expression by UniProt/SwissProt for CLCN3 Gene:

P51790-CLCN3_HUMAN
Tissue specificity: Expressed primarily in tissues derived from neuroectoderm. Within the brain, its expression is particularly evident in the hippocampus, olfactory cortex, and olfactory bulb. Highly expressed in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Also expressed in tracheal and alveolar epithelial cells, and intima and media of the pulmonary vessels. Expressed in bronchus and colon (at protein level).

Evidence on tissue expression from TISSUES for CLCN3 Gene

  • Intestine(4.5)
  • Muscle(4.5)
  • Nervous system(4.5)
  • Eye(4.4)
  • Lung(4.4)
  • Heart(2.5)
  • Kidney(2.4)
  • Pancreas(2.1)
genes like me logo Genes that share expression patterns with CLCN3: view

Primer Products

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLCN3 Gene

Orthologs for CLCN3 Gene

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

Orthologs for CLCN3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLCN3 33 34
  • 99.85 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CLCN3 34
  • 98 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CLCN3 34
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CLCN3 33 34
  • 94.07 (n)
mouse
(Mus musculus)
Mammalia Clcn3 33 16 34
  • 92.3 (n)
rat
(Rattus norvegicus)
Mammalia Clcn3 33
  • 91.56 (n)
cow
(Bos Taurus)
Mammalia CLCN3 33 34
  • 83.83 (n)
chicken
(Gallus gallus)
Aves CLCN3 33 34
  • 87.3 (n)
lizard
(Anolis carolinensis)
Reptilia CLCN3 34
  • 95 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia clcn3 33
  • 79.01 (n)
Str.5054 33
African clawed frog
(Xenopus laevis)
Amphibia Clcn3 33
zebrafish
(Danio rerio)
Actinopterygii clcn3 33 34
  • 74.84 (n)
Dr.10303 33
fruit fly
(Drosophila melanogaster)
Insecta ClC-c 33 34
  • 60.65 (n)
CG5284 35
  • 59 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005777 33
  • 59.81 (n)
worm
(Caenorhabditis elegans)
Secernentea clh-5 33 34
  • 57.24 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E22507g 33
  • 47.47 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GEF1 33 34 36
  • 47.35 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AEL071C 33
  • 46.27 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 59 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU06624 33
  • 50.68 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC19C7.11 33
  • 47.01 (n)
Species where no ortholog for CLCN3 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • 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 CLCN3 Gene

ENSEMBL:
Gene Tree for CLCN3 (if available)
TreeFam:
Gene Tree for CLCN3 (if available)

Paralogs for CLCN3 Gene

Paralogs for CLCN3 Gene

(4) SIMAP similar genes for CLCN3 Gene using alignment to 7 proteins:

Pseudogenes.org Pseudogenes for CLCN3 Gene

genes like me logo Genes that share paralogs with CLCN3: view

Variants for CLCN3 Gene

Sequence variations from dbSNP and Humsavar for CLCN3 Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs770732784 uncertain-significance, Progressive sensorineural hearing impairment 169,713,231(+) A/G coding_sequence_variant, missense_variant
rs1000053848 -- 169,656,737(+) G/A genic_upstream_transcript_variant, intron_variant
rs1000054081 -- 169,630,515(+) C/A genic_upstream_transcript_variant, intron_variant
rs10000743 -- 169,673,044(+) T/C intron_variant
rs1000090780 -- 169,633,773(+) T/C genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CLCN3 Gene

Variant ID Type Subtype PubMed ID
dgv5468n100 CNV gain 25217958
nsv4600 CNV insertion 18451855
nsv518832 CNV loss 19592680

Variation tolerance for CLCN3 Gene

Residual Variation Intolerance Score: 7.57% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.60; 30.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLCN3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLCN3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLCN3 Gene

Disorders for CLCN3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for CLCN3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cystic fibrosis
  • cf
- elite association - COSMIC cancer census association via MalaCards
Search CLCN3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CLCN3

genes like me logo Genes that share disorders with CLCN3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CLCN3 Gene

Publications for CLCN3 Gene

  1. The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. (PMID: 12471024) Gentzsch M … Riordan JR (The Journal of biological chemistry 2003) 3 4 22 58
  2. Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. (PMID: 20139089) Cuddapah VA … Sontheimer H (The Journal of biological chemistry 2010) 3 22 58
  3. Cardiac-specific overexpression of the human short CLC-3 chloride channel isoform in mice. (PMID: 18986326) Xiong D … Hume JR (Clinical and experimental pharmacology & physiology 2009) 3 22 58
  4. Overexpression of CLC-3 in HEK293T cells yields novel currents that are pH dependent. (PMID: 17977943) Matsuda JJ … Lamb FS (American journal of physiology. Cell physiology 2008) 3 22 58
  5. ClC-3 is required for LPA-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. (PMID: 18077605) Yin Z … Watsky MA (American journal of physiology. Cell physiology 2008) 3 22 58

Products for CLCN3 Gene

Sources for CLCN3 Gene

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