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Aliases for CLCN2 Gene

Aliases for CLCN2 Gene

  • Chloride Voltage-Gated Channel 2 2 3 5
  • Chloride Channel, Voltage-Sensitive 2 2 3
  • Chloride Channel 2 2 3
  • ClC-2 3 4
  • Chloride Channel Protein 2 3
  • CIC-2 3
  • EGI11 3
  • LKPAT 3
  • EJM6 3
  • CLC2 3
  • ECA2 3
  • ECA3 3
  • EGI3 3
  • EGMA 3
  • EJM8 3

External Ids for CLCN2 Gene

Previous GeneCards Identifiers for CLCN2 Gene

  • GC03P180523
  • GC03M185057
  • GC03M185466
  • GC03M185385
  • GC03M185546
  • GC03M184063
  • GC03M181470

Summaries for CLCN2 Gene

Entrez Gene Summary for CLCN2 Gene

  • This gene encodes a voltage-gated chloride channel. The encoded protein is a transmembrane protein that maintains chloride ion homeostasis in various cells. Defects in this gene may be a cause of certain epilepsies. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

GeneCards Summary for CLCN2 Gene

CLCN2 (Chloride Voltage-Gated Channel 2) is a Protein Coding gene. Diseases associated with CLCN2 include Leukoencephalopathy With Ataxia and Epilepsy, Idiopathic Generalized 11. Among its related pathways are Hepatic ABC Transporters and Activation of cAMP-Dependent PKA. GO annotations related to this gene include ion channel activity and voltage-gated chloride channel activity. An important paralog of this gene is CLCN1.

UniProtKB/Swiss-Prot for CLCN2 Gene

  • Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.

Gene Wiki entry for CLCN2 Gene

Additional gene information for CLCN2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCN2 Gene

Genomics for CLCN2 Gene

Regulatory Elements for CLCN2 Gene

Enhancers for CLCN2 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
GH03H184524 1.1 Ensembl ENCODE 11.3 -164.0 -164016 1 KLF1 ZIC2 HIC1 ZFHX2 GLIS2 ZNF366 POLR2A ZBTB48 PATZ1 PRDM10 MAGEF1 LINC02054 YEATS2 CHRD THPO LINC01840 CLCN2 POLR2H EPHB3 FAM131A
GH03H184360 1.4 ENCODE dbSUPER 8 -0.9 -855 4 HDGF PKNOX1 MLX ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 SLC30A9 CLCN2 POLR2H THPO
GH03H184417 0.9 ENCODE 10.8 -56.4 -56377 0 RB1 ARID4B SIN3A ZNF76 BMI1 RAD21 ZNF121 GLIS2 ZNF143 RUNX3 CHRD THPO LINC01840 EPHB3 FAM131A POLR2H CLCN2 EIF4G1 PSMD2 LINC02054
GH03H184359 0.6 Ensembl dbSUPER 0.7 +2.0 1951 0 L3MBTL2 KLHL24 CLCN2 PIR35526 GC03M184355
GH03H184354 1 ENCODE dbSUPER 0.4 +7.2 7194 0 HDGF CTCF MAZ ZNF740 TRIM22 REST RAD21 ZNF592 ZFHX2 GLIS2 GC03M184355 PIR35526 CLCN2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CLCN2 on UCSC Golden Path with GeneCards custom track

Genomic Location for CLCN2 Gene

Chromosome:
3
Start:
184,346,185 bp from pter
End:
184,361,651 bp from pter
Size:
15,467 bases
Orientation:
Minus strand

Genomic View for CLCN2 Gene

Genes around CLCN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCN2 Gene

Proteins for CLCN2 Gene

  • Protein details for CLCN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51788-CLCN2_HUMAN
    Recommended name:
    Chloride channel protein 2
    Protein Accession:
    P51788
    Secondary Accessions:
    • B4DQT9
    • B4DZ58
    • E9PBD9
    • E9PCD2
    • O14864
    • Q6IPA9
    • Q8WU13

    Protein attributes for CLCN2 Gene

    Size:
    898 amino acids
    Molecular mass:
    98535 Da
    Quaternary structure:
    No Data Available
    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 (By similarity).
    SequenceCaution:
    • Sequence=AAH21578.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};

    Alternative splice isoforms for CLCN2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLCN2 Gene

Post-translational modifications for CLCN2 Gene

No data available for DME Specific Peptides for CLCN2 Gene

Domains & Families for CLCN2 Gene

Gene Families for CLCN2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • FDA approved drug targets
  • Plasma proteins
  • Predicted membrane proteins
  • Transporters

Suggested Antigen Peptide Sequences for CLCN2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P51788

UniProtKB/Swiss-Prot:

CLCN2_HUMAN :
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
Family:
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
genes like me logo Genes that share domains with CLCN2: view

Function for CLCN2 Gene

Molecular function for CLCN2 Gene

GENATLAS Biochemistry:
chloride voltage-gated channel 2,widely expressed
UniProtKB/Swiss-Prot Function:
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.

Gene Ontology (GO) - Molecular Function for CLCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005247 voltage-gated chloride channel activity TAS,IEA --
GO:0005254 chloride channel activity IEA --
genes like me logo Genes that share ontologies with CLCN2: view
genes like me logo Genes that share phenotypes with CLCN2: view

Human Phenotype Ontology for CLCN2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLCN2 Gene

MGI Knock Outs for CLCN2:

Animal Model Products

CRISPR Products

miRNA for CLCN2 Gene

miRTarBase miRNAs that target CLCN2

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for CLCN2 Gene

Localization for CLCN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCN2 Gene

Cell membrane; Multi-pass membrane protein.

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 CLCN2 gene
Compartment Confidence
plasma membrane 5
extracellular 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CLCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0034707 chloride channel complex IEA --
genes like me logo Genes that share ontologies with CLCN2: view

Pathways & Interactions for CLCN2 Gene

genes like me logo Genes that share pathways with CLCN2: view

Pathways by source for CLCN2 Gene

Gene Ontology (GO) - Biological Process for CLCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 7795595
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IEA --
GO:0034220 ion transmembrane transport TAS,IEA --
GO:0034765 regulation of ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with CLCN2: view

No data available for SIGNOR curated interactions for CLCN2 Gene

Drugs & Compounds for CLCN2 Gene

(11) Drugs for CLCN2 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Lubiprostone Approved, Investigational Pharma Activator, activator, Target, inducer 46
Omeprazole Approved, Investigational, Vet_approved Pharma Activator, inhibitor H+,K+-ATPase inhibitor 355
arachidonic acid Experimental Nutra Activator 32
GaTx2 Pharma Channel blocker 0
NPPB Pharma Channel blocker inhibitor of chloride channel 0

(6) Additional Compounds for CLCN2 Gene - From: HMDB, Novoseek, and IUPHAR

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

(4) ApexBio Compounds for CLCN2 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 CLCN2: view

Drug Products

Transcripts for CLCN2 Gene

Unigene Clusters for CLCN2 Gene

Chloride channel, voltage-sensitive 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLCN2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17a · 17b ^ 18 ^ 19 ^ 20a · 20b ^ 21 ^ 22 ^
SP1: - -
SP2: - -
SP3:
SP4:

ExUns: 23 ^ 24
SP1:
SP2:
SP3:
SP4:

Relevant External Links for CLCN2 Gene

GeneLoc Exon Structure for
CLCN2
ECgene alternative splicing isoforms for
CLCN2

Expression for CLCN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLCN2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLCN2 Gene

This gene is overexpressed in Nerve - Tibial (x4.7).

Protein differential expression in normal tissues from HIPED for CLCN2 Gene

This gene is overexpressed in Testis (57.4) and Spinal cord (11.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CLCN2 Gene



Protein tissue co-expression partners for CLCN2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CLCN2 Gene:

CLCN2

SOURCE GeneReport for Unigene cluster for CLCN2 Gene:

Hs.436847

mRNA Expression by UniProt/SwissProt for CLCN2 Gene:

P51788-CLCN2_HUMAN
Tissue specificity: Ubiquitously expressed. Moderately expressed in aortic and coronary vascular smooth muscle cells and expressed at a low level in aortic endothelial cells.

Evidence on tissue expression from TISSUES for CLCN2 Gene

  • Lung(4.4)
  • Eye(4.2)
  • Muscle(4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CLCN2 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
  • skeletal muscle
  • skeleton
Organs:
Head and neck:
  • brain
  • head
  • meninges
  • neck
Limb:
  • lower limb
  • upper limb
General:
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with CLCN2: view

Primer Products

Orthologs for CLCN2 Gene

This gene was present in the common ancestor of animals.

Orthologs for CLCN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLCN2 33 34
  • 99.62 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 96 (a)
OneToMany
-- 34
  • 78 (a)
OneToMany
dog
(Canis familiaris)
Mammalia CLCN2 33 34
  • 91.28 (n)
cow
(Bos Taurus)
Mammalia CLCN2 33 34
  • 90.14 (n)
rat
(Rattus norvegicus)
Mammalia LOC100912455 33
  • 88.28 (n)
mouse
(Mus musculus)
Mammalia Clcn2 33 16 34
  • 88.09 (n)
oppossum
(Monodelphis domestica)
Mammalia CLCN2 34
  • 88 (a)
OneToOne
chicken
(Gallus gallus)
Aves CLCN2 33 34
  • 75.12 (n)
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 84 (a)
OneToMany
-- 34
  • 76 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia clcn2 33
  • 69.43 (n)
zebrafish
(Danio rerio)
Actinopterygii CLCN2 34
  • 72 (a)
OneToOne
LOC100333644 33
  • 70.35 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta GPRMGL4 33
  • 57.33 (n)
fruit fly
(Drosophila melanogaster)
Insecta ClC-a 33 34
  • 55.94 (n)
worm
(Caenorhabditis elegans)
Secernentea clh-3 35 33 34
  • 49.54 (n)
clh-2 34
  • 34 (a)
ManyToMany
clh-1 34
  • 32 (a)
ManyToMany
clh-4 34
  • 28 (a)
ManyToMany
Species where no ortholog for CLCN2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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 CLCN2 Gene

ENSEMBL:
Gene Tree for CLCN2 (if available)
TreeFam:
Gene Tree for CLCN2 (if available)

Paralogs for CLCN2 Gene

Paralogs for CLCN2 Gene

(3) SIMAP similar genes for CLCN2 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with CLCN2: view

Variants for CLCN2 Gene

Sequence variations from dbSNP and Humsavar for CLCN2 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs137852681 Uncertain significance, Juvenile absence epilepsy 2 (JAE2) [MIM:607628] 184,352,810(-) CACAG(A/G)GAGCG nc-transcript-variant, reference, missense
rs137852682 other, Epilepsy, idiopathic generalized 11 (EIG11) [MIM:607628] 184,353,787(-) GTACC(A/G)GGTGC nc-transcript-variant, reference, missense
rs587777111 Pathogenic, Leukoencephalopathy with ataxia (LKPAT) [MIM:615651] 184,354,556(+) CCACA(A/G/T)CGTAG nc-transcript-variant, reference, missense
rs71318369 other, Juvenile myoclonic epilepsy 8 (EJM8) [MIM:607628] 184,357,688(+) TGTTC(C/T)GGGAT intron-variant, nc-transcript-variant, reference, missense
rs141242566 Pathogenic 184,353,722(+) CAGGT(A/C/T)CCGGA nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for CLCN2 Gene

Variant ID Type Subtype PubMed ID
esv2422400 CNV duplication 17116639
nsv829813 CNV loss 17160897

Variation tolerance for CLCN2 Gene

Residual Variation Intolerance Score: 43.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.82; 93.42% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CLCN2 Gene

Human Gene Mutation Database (HGMD)
CLCN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLCN2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLCN2 Gene

Disorders for CLCN2 Gene

MalaCards: The human disease database

(16) MalaCards diseases for CLCN2 Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
leukoencephalopathy with ataxia
  • leukoencephalopathy with mild cerebellar ataxia and white matter edema
epilepsy, idiopathic generalized 11
  • epilepsy, juvenile myoclonic 8
leukoencephalopathy with ataxia due to clc-2 deficiency
  • leukoencephalopathy with ataxia
clcn2-related juvenile myoclonic epilepsy
juvenile absence epilepsy
  • epilepsy juvenile absence
- elite association - COSMIC cancer census association via MalaCards
Search CLCN2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CLCN2_HUMAN
  • Epilepsy, idiopathic generalized 11 (EIG11) [MIM:607628]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. {ECO:0000269 PubMed:19191339}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Juvenile absence epilepsy 2 (JAE2) [MIM:607628]: A subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures. {ECO:0000269 PubMed:12612585, ECO:0000269 PubMed:19710712}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
  • Juvenile myoclonic epilepsy 8 (EJM8) [MIM:607628]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. {ECO:0000269 PubMed:19191339}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Leukoencephalopathy with ataxia (LKPAT) [MIM:615651]: An autosomal recessive neurologic disorder with a characteristic pattern of white matter abnormalities on brain MRI. Affected individuals have prominent signal abnormalities and decreased apparent diffusion coefficient values in the posterior limbs of the internal capsules, middle cerebral peduncles, pyramidal tracts in the pons, and middle cerebellar peduncles, suggesting myelin microvacuolation. Clinical features include ataxia and unstable gait. More variable abnormalities may include visual field defects, headaches, and learning disabilities. {ECO:0000269 PubMed:23707145}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CLCN2

Genetic Association Database (GAD)
CLCN2
Human Genome Epidemiology (HuGE) Navigator
CLCN2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CLCN2
genes like me logo Genes that share disorders with CLCN2: view

No data available for Genatlas for CLCN2 Gene

Publications for CLCN2 Gene

  1. Two novel CLCN2 mutations accelerating chloride channel deactivation are associated with idiopathic generalized epilepsy. (PMID: 19191339) Saint-Martin C … Depienne C (Human mutation 2009) 3 4 22 45 60
  2. Alterations in the cytoplasmic domain of CLCN2 result in altered gating kinetics. (PMID: 17762171) Paul J … Kun JF (Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2007) 3 4 22 60
  3. CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity. (PMID: 15507145) Blaisdell CJ … Stine OC (BMC medical genetics 2004) 3 22 45 60
  4. Expression of CLCN voltage-gated chloride channel genes in human blood vessels. (PMID: 10198195) Lamb FS … Schutte BC (Journal of molecular and cellular cardiology 1999) 3 4 22 60
  5. Cloning of a putative human voltage-gated chloride channel (CIC-2) cDNA widely expressed in human tissues. (PMID: 7795595) Cid LP … Cutting GR (Human molecular genetics 1995) 2 3 4 60

Products for CLCN2 Gene

Sources for CLCN2 Gene

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