This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-lik... See more...

Aliases for CCN4 Gene

Aliases for CCN4 Gene

  • Cellular Communication Network Factor 4 2 3 5
  • WISP1 Overlapping Transcript 1 (Non-Protein Coding) 2 3
  • WNT1 Inducible Signaling Pathway Protein 1 2 3
  • WISP1 3'UTR-Associated RNA 1 2 3
  • CCN Family Member 4 3 4
  • WISP-1 2 4
  • WISP1 3 4
  • WNT1-Inducible-Signaling Pathway Protein 1 4
  • WNT1 Induced Secreted Protein 1 3
  • WISP1 Overlapping Transcript 1 2
  • Wnt-1-Induced Secreted Protein 4
  • WISP1-OT1 3
  • WISP1-UT1 3
  • WISP1tc 3
  • WISP1c 3
  • WISP1i 3
  • CCN4 5

External Ids for CCN4 Gene

Previous HGNC Symbols for CCN4 Gene

  • WISP1-OT1
  • WISP1-UT1
  • WISP1

Summaries for CCN4 Gene

Entrez Gene Summary for CCN4 Gene

  • This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is expressed at a high level in fibroblast cells, and overexpressed in colon tumors. The encoded protein binds to decorin and biglycan, two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue, and possibly prevents the inhibitory activity of decorin and biglycan in tumor cell proliferation. It also attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. It is 83% identical to the mouse protein at the amino acid level. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2011]

GeneCards Summary for CCN4 Gene

CCN4 (Cellular Communication Network Factor 4) is a Protein Coding gene. Diseases associated with CCN4 include Bladder Papillary Transitional Cell Neoplasm and Urinary Tract Papillary Transitional Cell Benign Neoplasm. Among its related pathways are Wnt signaling pathway. An important paralog of this gene is CCN2.

UniProtKB/Swiss-Prot Summary for CCN4 Gene

  • Downstream regulator in the Wnt/Frizzled-signaling pathway. Associated with cell survival. Attenuates p53-mediated apoptosis in response to DNA damage through activation of AKT kinase. Up-regulates the anti-apoptotic Bcl-X(L) protein. Adheres to skin and melanoma fibroblasts. In vitro binding to skin fibroblasts occurs through the proteoglycans, decorin and biglycan.

Gene Wiki entry for CCN4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CCN4 Gene

Genomics for CCN4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CCN4 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
GH08J133190 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 607.1 +1.4 1373 3.4 NR2F2 ZFHX2 EGR2 CCN4 HSALNG0068725 NDRG1
GH08J133189 Enhancer 0.2 Ensembl 600.7 -1.2 -1206 0.2 CCN4 HSALNG0068721 SLA
GH08J133051 Promoter/Enhancer 1.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 19.3 -126.2 -126213 25.8 FOXA1 RFX1 CEBPA MNT CEBPB RUNX3 CTCF USF1 FOS PKNOX1 SLA TG CCN4 TMEM71 PHF20L1 ENSG00000270137 5MWI_A-174 PTCSC1 lnc-NDRG1-4
GH08J133128 Promoter/Enhancer 1.5 EPDnew FANTOM5 ENCODE dbSUPER 17.2 -61.0 -60998 3.4 GATAD2A CEBPA CEBPB SP1 SMARCC1 ATF3 FOS JUND FOSL2 SIN3A SLA CCN4 TG ST3GAL1 PHF20L1 NDRG1 HSALNG0068721 HSALNG0068723
GH08J133080 Promoter/Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 17.2 -108.8 -108753 3.2 GABPA SP1 CEBPB NR2F2 CTCF CEBPG RAD21 RXRA POLR2A NR3C1 TMEM71 PHF20L1 CCN4 SLA ST3GAL1 TG lnc-NDRG1-4 5MWI_A-174
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CCN4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CCN4

Genomic Locations for CCN4 Gene

Genomic Locations for CCN4 Gene
chr8:133,190,907-133,231,690
(GRCh38/hg38)
Size:
40,784 bases
Orientation:
Plus strand
chr8:134,203,282-134,243,933
(GRCh37/hg19)
Size:
40,652 bases
Orientation:
Plus strand

Genomic View for CCN4 Gene

Genes around CCN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CCN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CCN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CCN4 Gene

Proteins for CCN4 Gene

  • Protein details for CCN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95388-CCN4_HUMAN
    Recommended name:
    CCN family member 4
    Protein Accession:
    O95388
    Secondary Accessions:
    • A8KAG6
    • E7EMM5
    • Q5JBS6
    • Q5JBS7
    • Q5JBS8
    • Q9HCS3

    Protein attributes for CCN4 Gene

    Size:
    367 amino acids
    Molecular mass:
    40331 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for CCN4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CCN4 Gene

Post-translational modifications for CCN4 Gene

  • Glycosylation at Asn284, Asn86, Asn343, and Asn143
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for CCN4 Gene

Domains & Families for CCN4 Gene

Gene Families for CCN4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted secreted proteins

Protein Domains for CCN4 Gene

InterPro:
Blocks:
  • Thrombospondin, type I
  • von Willebrand factor, type C
  • Insulin-like growth factor-binding protein, IGFBP
  • Cystine knot, C-terminal
  • Cystine knot domain
ProtoNet:

Suggested Antigen Peptide Sequences for CCN4 Gene

GenScript: Design optimal peptide antigens:
  • WISP1i (Q5JBS6_HUMAN)
  • cDNA FLJ54189, highly similar to WNT1-inducible signaling pathway protein 1 (Q5JBS7_HUMAN)
  • WISP1c (Q5JBS8_HUMAN)
  • Wnt-1-induced secreted protein (WISP1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95388

UniProtKB/Swiss-Prot:

CCN4_HUMAN :
  • Belongs to the CCN family.
Family:
  • Belongs to the CCN family.
genes like me logo Genes that share domains with CCN4: view

Function for CCN4 Gene

Molecular function for CCN4 Gene

UniProtKB/Swiss-Prot Function:
Downstream regulator in the Wnt/Frizzled-signaling pathway. Associated with cell survival. Attenuates p53-mediated apoptosis in response to DNA damage through activation of AKT kinase. Up-regulates the anti-apoptotic Bcl-X(L) protein. Adheres to skin and melanoma fibroblasts. In vitro binding to skin fibroblasts occurs through the proteoglycans, decorin and biglycan.

Phenotypes From GWAS Catalog for CCN4 Gene

Gene Ontology (GO) - Molecular Function for CCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005178 integrin binding IBA 21873635
GO:0005515 protein binding IPI 11598131
GO:0005520 insulin-like growth factor binding IEA --
GO:0008201 heparin binding IBA 21873635
genes like me logo Genes that share ontologies with CCN4: view
genes like me logo Genes that share phenotypes with CCN4: view

Animal Models for CCN4 Gene

MGI Knock Outs for CCN4:

Animal Model Products

  • Taconic Biosciences Mouse Models for CCN4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCN4

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CCN4 Gene

Localization for CCN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CCN4 Gene

Secreted.

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 CCN4 gene
Compartment Confidence
extracellular 5
cytosol 5
plasma membrane 3
cytoskeleton 2
nucleus 2
endoplasmic reticulum 2
mitochondrion 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space NAS 9843955
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA --
GO:0031012 extracellular matrix IBA 21873635
genes like me logo Genes that share ontologies with CCN4: view

Pathways & Interactions for CCN4 Gene

PathCards logo

SuperPathways for CCN4 Gene

SuperPathway Contained pathways
1 Wnt signaling pathway
genes like me logo Genes that share pathways with CCN4: view

Pathways by source for CCN4 Gene

1 KEGG pathway for CCN4 Gene

Interacting Proteins for CCN4 Gene

SIGNOR curated interactions for CCN4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001649 osteoblast differentiation IEA --
GO:0007155 cell adhesion IBA 21873635
GO:0007165 signal transduction TAS,IBA 21873635
GO:0007267 cell-cell signaling TAS 9843955
GO:0014911 positive regulation of smooth muscle cell migration ISS --
genes like me logo Genes that share ontologies with CCN4: view

Drugs & Compounds for CCN4 Gene

(1) Drugs for CCN4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with CCN4: view

Transcripts for CCN4 Gene

mRNA/cDNA for CCN4 Gene

4 REFSEQ mRNAs :
18 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CCN4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CCN4 Gene

No ASD Table

Relevant External Links for CCN4 Gene

GeneLoc Exon Structure for
CCN4

Expression for CCN4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CCN4

SOURCE GeneReport for Unigene cluster for CCN4 Gene:

Hs.492974

mRNA Expression by UniProt/SwissProt for CCN4 Gene:

O95388-CCN4_HUMAN
Tissue specificity: Expressed in heart, kidney, lung, pancreas, placenta, ovary, small intestine and spleen. Isoform 2 is expressed predominantly in scirrhous gastric carcinoma and, weakly in placenta. Overexpression is associated with several cancers including breast cancer and colon tumors. Isoform 2 is overexpressed in scirrhous gastric carcinoma.

Evidence on tissue expression from TISSUES for CCN4 Gene

  • Lung(4.4)
  • Kidney(3)
  • Nervous system(2.8)
  • Heart(2.5)
  • Muscle(2.3)
  • Intestine(2.3)
  • Lymph node(2.1)
  • Skin(2.1)
  • Bone(2.1)

No data available for mRNA expression in normal human tissues , mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CCN4 Gene

Orthologs for CCN4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CCN4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia WISP1 30 31
  • 99.55 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia WISP1 30 31
  • 86.1 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Wisp1 30 31
  • 83.47 (n)
OneToOne
Ccn4 17
Cow
(Bos Taurus)
Mammalia WISP1 30 31
  • 83.47 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Wisp1 30
  • 83.38 (n)
Oppossum
(Monodelphis domestica)
Mammalia WISP1 31
  • 70 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia WISP1 31
  • 57 (a)
OneToOne
Chicken
(Gallus gallus)
Aves WISP1 30 31
  • 69.45 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia WISP1 31
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia wisp1 30
  • 66.2 (n)
Zebrafish
(Danio rerio)
Actinopterygii wisp1b 30 31
  • 59.46 (n)
OneToMany
wisp1a 31
  • 57 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 38 (a)
ManyToMany
-- 31
  • 35 (a)
ManyToMany
Species where no ortholog for CCN4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for CCN4 Gene

ENSEMBL:
Gene Tree for CCN4 (if available)
TreeFam:
Gene Tree for CCN4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CCN4: view image

Paralogs for CCN4 Gene

Paralogs for CCN4 Gene

genes like me logo Genes that share paralogs with CCN4: view

Variants for CCN4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CCN4 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
716123 Likely Benign: not provided 133,225,381(+) C/T INTRON_VARIANT
721056 Likely Benign: not provided 133,220,665(+) C/T MISSENSE_VARIANT,INTRON_VARIANT
730932 Likely Benign: not provided 133,225,505(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT,INTRON_VARIANT
740749 Likely Benign: not provided 133,220,675(+) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT
783535 Benign: not provided 133,213,091(+) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for CCN4 Gene

Structural Variations from Database of Genomic Variants (DGV) for CCN4 Gene

Variant ID Type Subtype PubMed ID
esv1498080 CNV insertion 17803354
esv1593495 CNV insertion 17803354
nsv1132172 CNV deletion 24896259
nsv512967 CNV insertion 21212237
nsv958517 CNV insertion 24416366

Variation tolerance for CCN4 Gene

Residual Variation Intolerance Score: 85.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.90; 48.72% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CCN4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CCN4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CCN4 Gene

Disorders for CCN4 Gene

MalaCards: The human disease database

(5) MalaCards diseases for CCN4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
bladder papillary transitional cell neoplasm
  • urinary bladder papillary urothelial neoplasm
urinary tract papillary transitional cell benign neoplasm
  • inverted papilloma of urinary tract
breast cancer
  • breast lobular carcinoma
colorectal cancer
  • crc
pulmonary fibrosis, idiopathic
  • ipf
- elite association - COSMIC cancer census association via MalaCards
Search CCN4 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with CCN4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CCN4 Gene

Publications for CCN4 Gene

  1. WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. (PMID: 9843955) Pennica D … Levine AJ (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 23
  2. WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. (PMID: 11782444) Su F … Levine AJ (Genes & development 2002) 3 4 23
  3. WISP-1 binds to decorin and biglycan. (PMID: 11598131) Desnoyers L … Pennica D (The Journal of biological chemistry 2001) 3 4 23
  4. A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. (PMID: 11571650) Tanaka S … Sugimachi K (Oncogene 2001) 3 4 23
  5. Differential expression of the CCN family member WISP-1, WISP-2 and WISP-3 in human colorectal cancer and the prognostic implications. (PMID: 20372786) Davies SR … Jiang WG (International journal of oncology 2010) 3 23

Products for CCN4 Gene

Sources for CCN4 Gene