CCN4 (WISP1): A Multifunctional Matricellular Protein in Cancer and Fibrosis
Explore the gene, protein, expression, mutations, and clinical relevance of CCN4 (WISP1) with curated data from authoritative databases.
Gene Information Card
| Symbol | CCN4 |
|---|---|
| Full Name | Cellular Communication Network Factor 4 |
| Gene Type | protein coding |
| Chromosomal Location | 8q24.22 |
| NCBI Gene ID | 8840 ncbi.nlm.nih.gov/gene/8840 |
| Ensembl ID | ENSG00000104415 |
| UniProt ID | O95388 |
| OMIM ID | 603399 |
| HGNC ID | 12769 |
| Aliases | WISP1, WISP1-CCN4, CCN4, WISP1c, WISP1i |
Description
CCN4 (Cellular Communication Network Factor 4), also known as WISP1 (WNT1-inducible signaling pathway protein 1), is a secreted matricellular protein belonging to the CCN family. It plays critical roles in cell proliferation, adhesion, migration, and survival, and is involved in processes such as embryonic development, tissue repair, and fibrosis. CCN4 is frequently overexpressed in various cancers and contributes to tumor progression and metastasis. It also modulates WNT signaling and interacts with integrins and other extracellular matrix components.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression promotes tumor growth, invasion, and metastasis via activation of PI3K/AKT and WNT pathways | COSMIC; PubMed studies |
| Pulmonary fibrosis | Upregulation in fibrotic tissue; promotes fibroblast activation and extracellular matrix deposition | PubMed; UniProt |
| Osteoarthritis | Increased expression in chondrocytes; contributes to cartilage degradation | PubMed; OMIM |
| Cardiac fibrosis | Induced after myocardial infarction; promotes fibroblast proliferation and collagen synthesis | PubMed; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Lung | 8.7 | Low |
| Liver | 5.2 | Low |
| Kidney | 6.1 | Low |
| Pancreas | 4.5 | Low |
| Spleen | 3.8 | Low |
| Brain | 2.1 | Not detected |
| Testis | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 15.2 | High expression |
| MCF7 (Breast carcinoma) | 8.9 | Moderate |
| HepG2 (Liver carcinoma) | 6.3 | Low |
| HeLa (Cervical carcinoma) | 4.1 | Low |
| K562 (Leukemia) | 2.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1100C>T (p.Pro367Leu) | Missense | 0.01% (gnomAD) | Unknown; likely benign |
| c.1250A>G (p.Asn417Ser) | Missense | 0.005% | Unknown; possibly damaging |
| c.782G>A (p.Arg261His) | Missense | 0.002% | Unknown; not reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
No loss-of-function mutations have been characterized in CCN4; complete knockout in mice is viable but shows reduced bone mass and impaired wound healing.
Gain of Function (GOF)
Overexpression (not mutations) is the primary mechanism in cancer; no activating mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix organization | • cell adhesion |
| • cell proliferation | • cell migration |
| • WNT signaling pathway | • integrin binding |
| • heparin binding | • growth factor activity |
| • extracellular space | • endoplasmic reticulum lumen |
Pathways
• WNT signaling pathway
• PI3K-Akt signaling pathway
• Focal adhesion
• ECM-receptor interaction
• Hippo signaling pathway
Protein Summary
The CCN4 protein (UniProt O95388) is a secreted cysteine-rich protein of 367 amino acids (predicted mass ~40 kDa). It contains four conserved domains: IGF-binding domain, von Willebrand factor type C domain, thrombospondin type 1 domain, and a C-terminal cysteine knot domain. CCN4 is glycosylated and interacts with integrins (e.g., αvβ3, αvβ5) and heparan sulfate proteoglycans. It is involved in cell survival, proliferation, and differentiation. In cancer, CCN4 promotes epithelial-mesenchymal transition and metastasis. It is also implicated in fibrotic diseases and tissue regeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCN4 Knockout HEK293 Cell Line | EDJ-KQ2731 | Human | 8840 | Details Get a Quote |
| CCN4 Knockout HeLa Cell Line | EDJ-KQ55019 | Human | 8840 | Details Get a Quote |
| CCN4 Knockout A-549 Cell Line | EDJ-KQ63502 | Human | 8840 | Details Get a Quote |
| CCN4 Knockout HCT 116 Cell Line | EDJ-KQ71970 | Human | 8840 | Details Get a Quote |
