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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 Clcn4-Related X-Linked Intellectual Disability Syndrome. Among its related pathways are Hepatic ABC Transporters and Activation of cAMP-Dependent PKA. Gene Ontology (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

Additional gene information for CLCN4 Gene

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

Genomics for CLCN4 Gene

GeneHancer (GH) Regulatory Elements for CLCN4 Gene

Promoters and enhancers for CLCN4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ010155 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE 690.4 +0.4 404 2.9 MXI1 USF1 FOXA2 TAF1 SAP130 JUN ARID4B MAX SIN3A CEBPG CLCN4 PIR36102
GH0XJ010165 Enhancer 1.2 FANTOM5 Ensembl ENCODE 36 +9.4 9401 2.5 HDAC1 ATF1 NFRKB TCF12 GATA2 ETV6 IKZF2 RUNX3 CBFB ZNF592 CLCN4 PIR36102
GH0XJ010172 Enhancer 1 Ensembl ENCODE 34.3 +17.8 17780 4.5 ATF1 TAF9B ZBTB40 YY1 EGR1 FOS ATF7 RUNX3 CREM USF2 CLCN4 PIR36102
GH0XJ010198 Enhancer 1 FANTOM5 Ensembl ENCODE 22.4 +42.8 42829 3.1 CEBPB MAX JUNB CEBPG BATF IKZF1 ATF7 RUNX3 IKZF2 SPI1 PIR36102 CLCN4 WWC3
GH0XJ010160 Enhancer 0.3 FANTOM5 40.4 +4.1 4083 0.5 CLCN4 PIR36102
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLCN4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLCN4 gene promoter:
  • ATF
  • ATF-2
  • CRE-BP1
  • CREB
  • deltaCREB
  • c-Jun

Genomic Locations for CLCN4 Gene

Genomic Locations for CLCN4 Gene
80,716 bases
Plus strand
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

Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted membrane proteins
  • Transporters

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the chloride channel (TC 2.A.49) family. ClC-4/CLCN4 subfamily.
  • 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

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

Phenotypes From GWAS Catalog for CLCN4 Gene

Gene Ontology (GO) - Molecular Function for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005247 voltage-gated chloride channel activity IBA,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

Human Phenotype Ontology for CLCN4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLCN4 Gene

MGI Knock Outs for CLCN4:

Animal Model Products

  • Taconic Biosciences Mouse Models for CLCN4

CRISPR Products

miRNA for CLCN4 Gene

miRTarBase miRNAs that target CLCN4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCN4

Clone Products

No data available for Enzyme Numbers (IUBMB) , 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. Endoplasmic reticulum membrane.

Subcellular locations from

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 CLCN4 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
endosome 5
lysosome 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA,IDA 17023393
GO:0005887 integral component of plasma membrane IBA --
GO:0010008 endosome membrane TAS --
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

Gene Ontology (GO) - Biological Process for CLCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006821 chloride transport IDA,IMP 23647072
GO:0034220 ion transmembrane transport TAS --
GO:0055085 transmembrane transport IEA --
GO:1902476 chloride 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, Antagonist, Pore Blocker 0
Zn<sup>2+</sup> Pharma Positive, Allosteric regulator, Channel blocker, Inhibition, Potentiation, Agonist, Antagonist, Pore Blocker 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Chloride(1-)
  • Chlorine anion
  • CL(-)
  • Bertholite
  • Chloor
genes like me logo Genes that share compounds with CLCN4: view

Transcripts for CLCN4 Gene

mRNA/cDNA for CLCN4 Gene

Unigene Clusters for CLCN4 Gene

Chloride channel, voltage-sensitive 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCN4

Clone 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 from GTEx, Illumina, BioGPS, and CGAP SAGE 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, 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.

Evidence on tissue expression from TISSUES for CLCN4 Gene

  • Nervous system(4.9)
  • Eye(4.4)
  • Muscle(4.4)
genes like me logo Genes that share expression patterns with CLCN4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CLCN4 Gene

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 34
  • 100 (a)
(Monodelphis domestica)
Mammalia CLCN4 34
  • 98 (a)
(Ornithorhynchus anatinus)
Mammalia CLCN4 34
  • 97 (a)
(Canis familiaris)
Mammalia CLCN4 34 33
  • 91.45 (n)
(Bos Taurus)
Mammalia CLCN4 34 33
  • 90.22 (n)
(Mus musculus)
Mammalia Clcn4-2 34 33
  • 88.26 (n)
Clcn4 16
(Rattus norvegicus)
Mammalia Clcn4 33
  • 87.93 (n)
(Gallus gallus)
Aves CLCN4 34 33
  • 81.27 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 23 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia clcn4 33
  • 78.64 (n)
Str.12434 33
(Danio rerio)
Actinopterygii clcn4 34 33
  • 78.18 (n)
Dr.7965 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.174 33
fruit fly
(Drosophila melanogaster)
Insecta CG5284 35
  • 57 (a)
ClC-c 34
  • 51 (a)
(Caenorhabditis elegans)
Secernentea clh-5 34
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GEF1 34
  • 30 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 58 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU06444 33
  • 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)
Evolutionary constrained regions (ECRs) for CLCN4: view image

Paralogs for CLCN4 Gene

Paralogs for CLCN4 Gene

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

  • B7Z5Z4_HUMAN
  • Q4G0X3_HUMAN
  • Q75N13_HUMAN
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 Variation AA Info Type
rs192492405 benign, likely-benign, uncertain-significance, not specified, not provided 10,187,618(+) C/G/T intron_variant
rs587777161 pathogenic, Mental retardation 49, X-linked, not provided, CLCN4-related disorder, Mental retardation, X-linked 49 (MRX49) [MIM:300114] 10,213,734(+) G/A/C coding_sequence_variant, missense_variant
rs879255580 pathogenic, CLCN4-related disorder 10,206,437(+) T/G coding_sequence_variant, missense_variant
rs879255581 pathogenic, CLCN4-related disorder 10,206,464(+) T/C coding_sequence_variant, missense_variant
rs879255582 pathogenic, CLCN4-related disorder 10,213,705(+) C/T coding_sequence_variant, missense_variant

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)

Additional Variant Information for CLCN4 Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for CLCN4 Gene

MalaCards: The human disease database

(6) MalaCards diseases for CLCN4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
mental retardation, x-linked 49
  • mrx49
clcn4-related x-linked intellectual disability syndrome
x-linked non-specific intellectual disability
  • x-linked non-syndromic intellectual disability
ocular albinism
  • albinism, ocular
dent disease 1
  • nephrolithiasis, hypercalciuric, x-linked
- elite association - COSMIC cancer census association via MalaCards
Search CLCN4 in MalaCards View complete list of genes associated with diseases


  • Mental retardation, X-linked 49 (MRX49) [MIM:300114]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269 PubMed:23647072, ECO:0000269 PubMed:25644381}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CLCN4

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

No data available for 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 MA … Ballabio A (Human molecular genetics 1994) 2 3 4 22 58
  2. Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. (PMID: 16034421) Picollo A … Pusch M (Nature 2005) 2 3 22 58
  3. Identification of an acid-activated Cl(-) channel from human skeletal muscles. (PMID: 10564087) Kawasaki M … Sasaki S (The American journal of physiology 1999) 3 4 22 58
  4. X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. (PMID: 25644381) Hu H … Kalscheuer VM (Molecular psychiatry 2016) 3 4 58
  5. Exome sequencing reveals new causal mutations in children with epileptic encephalopathies. (PMID: 23647072) Veeramah KR … Hammer MF (Epilepsia 2013) 3 4 58

Products for CLCN4 Gene

Sources for CLCN4 Gene

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