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Aliases for CLCA4 Gene

Aliases for CLCA4 Gene

  • Chloride Channel Accessory 4 2 3 4 5
  • Chloride Channel, Calcium Activated, Family Member 4 2 3
  • Calcium-Activated Chloride Channel Family Member 4 3 4
  • Calcium-Activated Chloride Channel Protein 2 3 4
  • Chloride Channel Regulator 4 2 3
  • HCaCC-2 3 4
  • CaCC-2 3 4
  • HCLCA4 3 4
  • CaCC2 3 4
  • Calcium-Activated Chloride Channel Regulator 4 3
  • EC 3.4.-.- 4
  • CaCC 3

External Ids for CLCA4 Gene

Previous GeneCards Identifiers for CLCA4 Gene

  • GC01P087514
  • GC01P086181
  • GC01P086305
  • GC01P086435
  • GC01P086724
  • GC01P087012
  • GC01P085123

Summaries for CLCA4 Gene

Entrez Gene Summary for CLCA4 Gene

  • The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Alternative splicing results in multiple transcript variants, only one of which is thought to be protein coding. [provided by RefSeq, Dec 2008]

GeneCards Summary for CLCA4 Gene

CLCA4 (Chloride Channel Accessory 4) is a Protein Coding gene. Diseases associated with CLCA4 include Cystic Fibrosis and Bestrophinopathy. Among its related pathways are Hepatic ABC Transporters and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include metallopeptidase activity and intracellular calcium activated chloride channel activity. An important paralog of this gene is CLCA1.

UniProtKB/Swiss-Prot for CLCA4 Gene

  • May be involved in mediating calcium-activated chloride conductance.

Gene Wiki entry for CLCA4 Gene

Additional gene information for CLCA4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLCA4 Gene

Genomics for CLCA4 Gene

GeneHancer (GH) Regulatory Elements for CLCA4 Gene

Promoters and enhancers for CLCA4 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
GH01J086546 Promoter/Enhancer 0.7 EPDnew ENCODE 650.7 +0.0 7 1.3 CLCA4 CDCA4P2
GH01J086548 Enhancer 0.2 ENCODE 650.7 +1.8 1821 1.1 CLCA4 CLCA3P CDCA4P2
GH01J086523 Enhancer 0.3 FANTOM5 11.6 -23.5 -23461 0.2 CLCA4 LOC105378826
GH01J086517 Enhancer 0.2 ENCODE 11.1 -29.5 -29543 0.2 CLCA4 CLCA1 CLCA2 LOC105378826 LOC105378827
GH01J086526 Enhancer 0.4 ENCODE 5.2 -19.5 -19522 1.4 USF1 JUN CLCA4 LOC105378826
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLCA4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLCA4 gene promoter:
  • FOXL1
  • LCR-F1
  • S8
  • NF-E2 p45
  • NF-E2
  • Evi-1
  • POU3F1
  • Bach1
  • Bach2
  • JunD

Genomic Locations for CLCA4 Gene

Genomic Locations for CLCA4 Gene
33,683 bases
Plus strand
33,679 bases
Plus strand

Genomic View for CLCA4 Gene

Genes around CLCA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLCA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLCA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLCA4 Gene

Proteins for CLCA4 Gene

  • Protein details for CLCA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Calcium-activated chloride channel regulator 4
    Protein Accession:
    Secondary Accessions:
    • A8MQC9
    • B7Z1Q5
    • Q6UX81
    • Q9UNF7

    Protein attributes for CLCA4 Gene

    919 amino acids
    Molecular mass:
    101283 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for CLCA4 Gene


neXtProt entry for CLCA4 Gene

Post-translational modifications for CLCA4 Gene

  • The translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a N-terminal and a C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.
  • Glycosylation at Asn852, Asn837, Asn832, Asn811, Asn628, Asn588, Asn542, posLast=504504, posLast=340340, and Asn75
  • Modification sites at PhosphoSitePlus

Other Protein References for CLCA4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CLCA4 Gene

Domains & Families for CLCA4 Gene

Gene Families for CLCA4 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for CLCA4 Gene

Graphical View of Domain Structure for InterPro Entry



  • The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.
  • Belongs to the CLCR family.
  • The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.
  • Belongs to the CLCR family.
genes like me logo Genes that share domains with CLCA4: view

Function for CLCA4 Gene

Molecular function for CLCA4 Gene

UniProtKB/Swiss-Prot Function:
May be involved in mediating calcium-activated chloride conductance.
UniProtKB/Swiss-Prot Induction:
Down-regulated in oral tongue squamous cell carcinomas.

Enzyme Numbers (IUBMB) for CLCA4 Gene

Phenotypes From GWAS Catalog for CLCA4 Gene

Gene Ontology (GO) - Molecular Function for CLCA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity TAS --
GO:0005229 intracellular calcium activated chloride channel activity IBA --
GO:0005254 chloride channel activity TAS 10437792
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
genes like me logo Genes that share ontologies with CLCA4: view
genes like me logo Genes that share phenotypes with CLCA4: view

Human Phenotype Ontology for CLCA4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLCA4 Gene

MGI Knock Outs for CLCA4:

Animal Model Products

CRISPR Products

miRNA for CLCA4 Gene

miRTarBase miRNAs that target CLCA4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCA4

No data available for Transcription Factor Targets and HOMER Transcription for CLCA4 Gene

Localization for CLCA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLCA4 Gene

Cell membrane; Single-pass membrane protein. Apical cell membrane. Secreted. Note=The C-terminus 30 kDa form is anchored to the membrane. The N-terminus 110 kDa form is released from the membrane triggered by an unknown stimulus. {ECO:0000250}.

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 CLCA4 gene
Compartment Confidence
plasma membrane 5
extracellular 5
nucleus 2
cytoskeleton 1
cytosol 1

Gene Ontology (GO) - Cellular Components for CLCA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 10437792
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with CLCA4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CLCA4 Gene

Pathways & Interactions for CLCA4 Gene

genes like me logo Genes that share pathways with CLCA4: view

Interacting Proteins for CLCA4 Gene

STRING Interaction Network Preview (showing 2 interactants - click image to see details)
Selected Interacting proteins: Q14CN2-CLCA4_HUMAN ENSP00000359594 for CLCA4 Gene via IID STRING

Gene Ontology (GO) - Biological Process for CLCA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006821 chloride transport IEA --
GO:0034220 ion transmembrane transport TAS --
GO:1902476 chloride transmembrane transport IEA --
genes like me logo Genes that share ontologies with CLCA4: view

No data available for SIGNOR curated interactions for CLCA4 Gene

Drugs & Compounds for CLCA4 Gene

(5) Drugs for CLCA4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Talniflumate Approved Pharma CaCC blocker and Cl-/HCO3- exchange inhibitor 0
calcium Approved Nutra 0
CaCCinh-A01 Pharma 0
Eact Pharma Activator of Ca2+-activated Cl- channel transmembrane protein 16A (TMEM16A) 0
T16Ainh - A01 Pharma 0

(1) Additional Compounds for CLCA4 Gene - From: HMDB

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 CLCA4: view

Transcripts for CLCA4 Gene

mRNA/cDNA for CLCA4 Gene

Unigene Clusters for CLCA4 Gene

Chloride channel accessory 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLCA4

Alternative Splicing Database (ASD) splice patterns (SP) for CLCA4 Gene

No ASD Table

Relevant External Links for CLCA4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CLCA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLCA4 Gene

mRNA differential expression in normal tissues according to GTEx for CLCA4 Gene

This gene is overexpressed in Esophagus - Mucosa (x22.8), Colon - Transverse (x13.3), and Minor Salivary Gland (x6.0).

Protein differential expression in normal tissues from HIPED for CLCA4 Gene

This gene is overexpressed in Cervix (39.6), Nasal epithelium (13.0), and Colon (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CLCA4 Gene

Protein tissue co-expression partners for CLCA4 Gene

NURSA nuclear receptor signaling pathways regulating expression of CLCA4 Gene:


SOURCE GeneReport for Unigene cluster for CLCA4 Gene:


mRNA Expression by UniProt/SwissProt for CLCA4 Gene:

Tissue specificity: Primarily expressed in the digestive tract, mainly in colon. Detected in smaller amounts in brain, urogenital organs, testis, and salivary and mammary glands. Highly expressed in the epithelial layer and submucosal gland of the inferior turbinate mucosa. Lower levels in the epithelial layer of nasal polyp.

Evidence on tissue expression from TISSUES for CLCA4 Gene

  • Intestine(4.5)
  • Nervous system(4.4)
  • Saliva(4)
genes like me logo Genes that share expression patterns with CLCA4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLCA4 Gene

Orthologs for CLCA4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CLCA4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia CLCA4 34 33
  • 98.95 (n)
(Canis familiaris)
Mammalia CLCA4 34 33
  • 85.32 (n)
(Bos Taurus)
Mammalia CLCA4 34 33
  • 82.39 (n)
(Mus musculus)
Mammalia AI747448 34 33
  • 76.9 (n)
Gm6289 34
  • 70 (a)
Clca6 34
  • 69 (a)
Clca4b 16
(Rattus norvegicus)
Mammalia Clca4 33
  • 76.67 (n)
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 56 (a)
-- 34
  • 55 (a)
-- 34
  • 54 (a)
-- 34
  • 53 (a)
-- 34
  • 47 (a)
-- 34
  • 44 (a)
(Monodelphis domestica)
Mammalia -- 34
  • 49 (a)
-- 34
  • 38 (a)
(Gallus gallus)
Aves -- 34
  • 47 (a)
(Anolis carolinensis)
Reptilia -- 34
  • 47 (a)
-- 34
  • 47 (a)
-- 34
  • 47 (a)
-- 34
  • 45 (a)
-- 34
  • 44 (a)
-- 34
  • 44 (a)
-- 34
  • 44 (a)
-- 34
  • 44 (a)
-- 34
  • 41 (a)
(Danio rerio)
Actinopterygii si:dkey-243k1.4 34
  • 41 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 38 (a)
-- 34
  • 33 (a)
-- 34
  • 29 (a)
-- 34
  • 28 (a)
-- 34
  • 26 (a)
Species where no ortholog for CLCA4 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)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CLCA4 Gene

Gene Tree for CLCA4 (if available)
Gene Tree for CLCA4 (if available)
Evolutionary constrained regions (ECRs) for CLCA4: view image

Paralogs for CLCA4 Gene

Paralogs for CLCA4 Gene

(3) SIMAP similar genes for CLCA4 Gene using alignment to 3 proteins:

  • L8ECE0_HUMAN Pseudogenes for CLCA4 Gene

genes like me logo Genes that share paralogs with CLCA4: view

Variants for CLCA4 Gene

Sequence variations from dbSNP and Humsavar for CLCA4 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000064671 -- 86,572,631(+) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1000091891 -- 86,562,168(+) G/A intron_variant
rs1000372816 -- 86,568,561(+) A/C intron_variant
rs1000580072 -- 86,578,501(+) T/C intron_variant
rs1000744372 -- 86,551,673(+) C/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CLCA4 Gene

Variant ID Type Subtype PubMed ID
dgv357n54 CNV loss 21841781
dgv358n54 CNV loss 21841781
dgv61e212 CNV loss 25503493
esv2670523 CNV deletion 23128226
esv2761188 CNV gain+loss 21179565
esv3565359 CNV deletion 23714750
esv3586700 CNV gain 21293372
esv3586701 CNV loss 21293372
nsv546759 CNV loss 21841781
nsv546760 CNV gain 21841781
nsv546761 CNV loss 21841781
nsv546764 CNV loss 21841781
nsv546767 CNV loss 21841781
nsv546771 CNV loss 21841781
nsv823464 CNV loss 20364138

Variation tolerance for CLCA4 Gene

Residual Variation Intolerance Score: 21.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.21; 69.90% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLCA4 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 CLCA4 Gene

Disorders for CLCA4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for CLCA4 Gene - From: HGMD, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
cystic fibrosis
  • cf
  • bestrophinopathy, autosomal recessive
farber lipogranulomatosis
  • frbrl
- elite association - COSMIC cancer census association via MalaCards
Search CLCA4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CLCA4

genes like me logo Genes that share disorders with CLCA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CLCA4 Gene

Publications for CLCA4 Gene

  1. Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea. (PMID: 10437792) Agnel M … Culouscou JM (FEBS letters 1999) 2 3 4 58
  2. The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis. (PMID: 15490240) Ritzka M … Tümmler B (Human genetics 2004) 3 4 58
  3. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. (PMID: 12975309) Clark HF … Gray A (Genome research 2003) 3 4 58
  4. Systematic identification of pathological lamin A interactors. (PMID: 24623722) Dittmer TA … Misteli T (Molecular biology of the cell 2014) 3 58
  5. Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. (PMID: 23376485) Prunotto M … Moll S (Journal of proteomics 2013) 3 58

Products for CLCA4 Gene

Sources for CLCA4 Gene

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