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Aliases for CLCN4 Gene

Aliases for CLCN4 Gene

  • Chloride Voltage-Gated Channel 4 2 3 5
  • Chloride Channel, Voltage-Sensitive 4 2 3
  • Chloride Channel Protein 4 3 4
  • Chloride Transporter ClC-4 3 4
  • Chloride Channel 4 2 3
  • ClC-4 3 4
  • H(+)/Cl(-) Exchange Transporter 4 3
  • ClC-4A 3
  • MRX15 3
  • MRX49 3
  • CLC4 3

External Ids for CLCN4 Gene

Previous GeneCards Identifiers for CLCN4 Gene

  • GC0XP009154
  • GC0XP008940
  • GC0XP009471
  • GC0XP009536
  • GC0XP009934
  • GC0XP007954

Summaries for CLCN4 Gene

Entrez Gene Summary for CLCN4 Gene

  • The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. Chloride channel 4 has an evolutionary conserved CpG island and is conserved in both mouse and hamster. This gene is mapped in close proximity to APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), which are both located on the human X chromosome at band p22.3. The physiological role of chloride channel 4 remains unknown but may contribute to the pathogenesis of neuronal disorders. Alternate splicing results in two transcript variants that encode different proteins. [provided by RefSeq, Mar 2012]

GeneCards Summary for CLCN4 Gene

CLCN4 (Chloride Voltage-Gated Channel 4) is a Protein Coding gene. Diseases associated with CLCN4 include Mental Retardation, X-Linked 49 and Non-Syndromic X-Linked Intellectual Disability. 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 CLCN5.

UniProtKB/Swiss-Prot for CLCN4 Gene

  • Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons.

Gene Wiki entry for CLCN4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCN4 Gene

Genomics for CLCN4 Gene

Regulatory Elements for CLCN4 Gene

Enhancers for CLCN4 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
GH0XF010160 0.5 FANTOM5 40.4 +4.1 4084 0.5 CLCN4 PIR36102
GH0XF010155 0.6 ENCODE 40.4 +0.3 256 2.6 TBP USF1 SAP130 TAF1 JUN ARID4B MAX CEBPG YY1 POLR2A CLCN4 PIR36102
GH0XF010165 1.4 FANTOM5 Ensembl ENCODE 36 +9.8 9805 3.5 CREB3L1 YY1 GATA2 ETV6 CEBPB ELF1 REST TFDP1 ZNF589 CEBPA CLCN4 PIR36102
GH0XF010172 0.9 Ensembl ENCODE 34.3 +17.8 17786 4.5 GTF2F1 TEAD4 EBF1 ZBTB40 YY1 ZNF316 FOS NFE2 CREM MAFK CLCN4 PIR36102
GH0XF010198 1.5 FANTOM5 Ensembl ENCODE 22.3 +42.8 42829 3.1 ATF1 CREB3L1 NFRKB YY1 ETV6 CBFB CEBPB JUNB TBX21 TFDP1 CLCN4 WWC3 PIR36102
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around CLCN4 on UCSC Golden Path with GeneCards custom track

Promoters for CLCN4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001488274 755 2601 TBP ATF1 USF1 SAP130 TAF1 TAL1 JUN ARID4B MAX CEBPG

Genomic Location for CLCN4 Gene

10,156,945 bp from pter
10,237,660 bp from pter
80,716 bases
Plus strand

Genomic View for CLCN4 Gene

Genes around CLCN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCN4 Gene

Proteins for CLCN4 Gene

  • Protein details for CLCN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    H(+)/Cl(-) exchange transporter 4
    Protein Accession:
    Secondary Accessions:
    • A1L3U1
    • B7Z5Z4
    • Q9UBU1

    Protein attributes for CLCN4 Gene

    760 amino acids
    Molecular mass:
    84917 Da
    Quaternary structure:
    No Data Available
    • 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.

    Alternative splice isoforms for CLCN4 Gene


neXtProt entry for CLCN4 Gene

Post-translational modifications for CLCN4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CLCN4 Gene

No data available for DME Specific Peptides for CLCN4 Gene

Domains & Families for CLCN4 Gene

Gene Families for CLCN4 Gene

Graphical View of Domain Structure for InterPro Entry



  • Contains 2 CBS domains.
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-4/CLCN4 subfamily.
  • Contains 2 CBS domains.
  • Belongs to the chloride channel (TC 2.A.49) family. ClC-4/CLCN4 subfamily.
genes like me logo Genes that share domains with CLCN4: view

Function for CLCN4 Gene

Molecular function for CLCN4 Gene

GENATLAS Biochemistry:
chloride voltage-gated channel 4,brain and heart
UniProtKB/Swiss-Prot Function:
Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons.

Gene Ontology (GO) - Molecular Function for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005247 voltage-gated chloride channel activity IEA,TAS --
GO:0005254 chloride channel activity IDA 10564087
GO:0005524 ATP binding IEA --
GO:0015297 antiporter activity TAS --
genes like me logo Genes that share ontologies with CLCN4: view
genes like me logo Genes that share phenotypes with CLCN4: view

Animal Models for CLCN4 Gene

MGI Knock Outs for CLCN4:

Animal Model Products

  • Taconic Biosciences Mouse Models for CLCN4

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CLCN4 Gene

Localization for CLCN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCN4 Gene

Early endosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein.

Subcellular locations from

Jensen Localization Image for CLCN4 Gene COMPARTMENTS Subcellular localization image for CLCN4 gene
Compartment Confidence
endosome 5
plasma membrane 4
lysosome 1
peroxisome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005789 endoplasmic reticulum membrane IDA 17023393
GO:0005887 integral component of plasma membrane IBA --
GO:0010008 endosome membrane TAS --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with CLCN4: view

Pathways & Interactions for CLCN4 Gene

genes like me logo Genes that share pathways with CLCN4: view

Interacting Proteins for CLCN4 Gene

Gene Ontology (GO) - Biological Process for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport TAS 8069296
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IMP,IDA 23647072
GO:0034220 ion transmembrane transport TAS --
GO:0055085 transmembrane transport IEA --
genes like me logo Genes that share ontologies with CLCN4: view

No data available for SIGNOR curated interactions for CLCN4 Gene

Drugs & Compounds for CLCN4 Gene

(2) Drugs for CLCN4 Gene - From: DGIdb and IUPHAR

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cd<sup>2+</sup> Pharma Channel blocker 0
Zn<sup>2+</sup> Pharma Positive, Allosteric regulator 0

(4) Additional Compounds for CLCN4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
genes like me logo Genes that share compounds with CLCN4: view

Transcripts for CLCN4 Gene

Unigene Clusters for CLCN4 Gene

Chloride channel, voltage-sensitive 4:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLCN4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14
SP1: - -
SP2: - -
SP3: - - - -
SP4: - - -

Relevant External Links for CLCN4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CLCN4 Gene

mRNA expression in normal human tissues for CLCN4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLCN4 Gene

This gene is overexpressed in Muscle - Skeletal (x6.6) and Brain - Frontal Cortex (BA9) (x4.1).

Protein differential expression in normal tissues from HIPED for CLCN4 Gene

This gene is overexpressed in Frontal cortex (36.5) and Retina (32.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CLCN4 Gene

Protein tissue co-expression partners for CLCN4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CLCN4 Gene:


SOURCE GeneReport for Unigene cluster for CLCN4 Gene:


mRNA Expression by UniProt/SwissProt for CLCN4 Gene:

Tissue specificity: Abundant in skeletal muscle and also detectable in brain and heart.
genes like me logo Genes that share expression patterns with CLCN4: view

Primer Products

Orthologs for CLCN4 Gene

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

Orthologs for CLCN4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia CLCN4 35
  • 100 (a)
(Monodelphis domestica)
Mammalia CLCN4 35
  • 98 (a)
(Ornithorhynchus anatinus)
Mammalia CLCN4 35
  • 97 (a)
(Canis familiaris)
Mammalia CLCN4 34 35
  • 91.45 (n)
(Bos Taurus)
Mammalia CLCN4 34 35
  • 90.22 (n)
(Mus musculus)
Mammalia Clcn4-2 34 35
  • 88.26 (n)
Clcn4 16
(Rattus norvegicus)
Mammalia Clcn4 34
  • 87.93 (n)
(Gallus gallus)
Aves CLCN4 34 35
  • 81.27 (n)
(Anolis carolinensis)
Reptilia -- 35
  • 23 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia clcn4 34
  • 78.64 (n)
Str.12434 34
(Danio rerio)
Actinopterygii clcn4 34 35
  • 78.18 (n)
Dr.7965 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.174 34
fruit fly
(Drosophila melanogaster)
Insecta CG5284 36
  • 57 (a)
ClC-c 35
  • 51 (a)
(Caenorhabditis elegans)
Secernentea clh-5 35
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GEF1 35
  • 30 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 58 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU06444 34
  • 52.05 (n)
Species where no ortholog for CLCN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)
  • 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 CLCN4 Gene

Gene Tree for CLCN4 (if available)
Gene Tree for CLCN4 (if available)

Paralogs for CLCN4 Gene

Paralogs for CLCN4 Gene

(2) SIMAP similar genes for CLCN4 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with CLCN4: view

Variants for CLCN4 Gene

Sequence variations from dbSNP and Humsavar for CLCN4 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
rs587777161 Pathogenic 10,213,734(+) TAACC(A/G)GGGGT reference, missense
rs879255580 Pathogenic 10,206,437(+) GCTGG(G/T)GCTGG reference, missense
rs879255581 Pathogenic 10,206,464(+) GAGCC(C/T)TGGGA reference, missense
rs879255582 Pathogenic 10,213,705(+) GGTGT(C/T)ATTGG reference, missense
rs879255583 Pathogenic 10,213,768(+) GGCGG(C/T)GGCTG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for CLCN4 Gene

Variant ID Type Subtype PubMed ID
esv2758861 CNV loss 17122850
esv3573566 CNV loss 25503493
nsv519068 CNV gain 19592680
nsv6795 CNV insertion 18451855

Variation tolerance for CLCN4 Gene

Residual Variation Intolerance Score: 4.14% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.47; 10.31% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CLCN4 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLCN4 Gene

Disorders for CLCN4 Gene

MalaCards: The human disease database

(4) MalaCards diseases for CLCN4 Gene - From: ClinVar, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
mental retardation, x-linked 49
  • mental retardation, x-linked 15
non-syndromic x-linked intellectual disability
  • mrx
ocular albinism
  • xloa
dent disease
  • dent disease 2
- elite association - COSMIC cancer census association via MalaCards
Search CLCN4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for CLCN4

Genetic Association Database (GAD)
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with CLCN4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CLCN4 Gene

Publications for CLCN4 Gene

  1. A gene from the Xp22.3 region shares homology with voltage-gated chloride channels. (PMID: 8069296) van Slegtenhorst M.A. … Ballabio A. (Hum. Mol. Genet. 1994) 2 3 4 22 64
  2. Identification of an acid-activated Cl- channel from human skeletal muscles. (PMID: 10564087) Kawasaki M. … Sasaki S. (Am. J. Physiol. 1999) 3 4 22 64
  3. Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases. (PMID: 20087350) Ishiguro T. … Boyd D.D. (Br. J. Cancer 2010) 3 22 64
  4. Mutational analysis of CLC-5, cofilin and CLC-4 in patients with Dent's disease. (PMID: 19546591) Wu F. … Thakker R.V. (Nephron Physiol 2009) 3 22 64
  5. Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (PMID: 16034421) Picollo A. … Pusch M. (Nature 2005) 3 22 64

Products for CLCN4 Gene

Sources for CLCN4 Gene

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