CCN6 (Cellular Communication Network Factor 6)
A matricellular protein involved in growth regulation, chondrogenesis, and cancer suppression
Gene Information Card
| Symbol | CCN6 |
|---|---|
| Full Name | Cellular Communication Network Factor 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q22.33 |
| NCBI Gene ID | 8838 ncbi.nlm.nih.gov/gene/8838 |
| Ensembl ID | ENSG00000112761 |
| UniProt ID | O95389 |
| OMIM ID | 603400 |
| HGNC ID | 12771 |
| Aliases | WISP3, WNT1 inducible signaling pathway protein 3, LIBC, PPAC, PPD |
Description
CCN6 (Cellular Communication Network Factor 6), also known as WISP3, is a member of the CCN (CYR61/CTGF/NOV) family of matricellular proteins. It is involved in cell growth, differentiation, adhesion, and migration. CCN6 plays a critical role in chondrogenesis and skeletal development. Loss-of-function mutations in CCN6 cause progressive pseudorheumatoid dysplasia (PPD), a rare autosomal recessive disorder characterized by joint stiffness and cartilage degeneration. CCN6 also functions as a tumor suppressor in several cancers, including breast and colorectal cancer, by modulating Wnt signaling and inhibiting epithelial-mesenchymal transition.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Progressive pseudorheumatoid dysplasia (PPD) | Loss-of-function mutations in CCN6 disrupt chondrocyte differentiation and extracellular matrix maintenance, leading to progressive joint degeneration. | OMIM #603400; PMID: 10441331 |
| Breast cancer | Reduced CCN6 expression promotes tumor growth and metastasis via activation of Wnt/β-catenin signaling and EMT. | PMID: 17699752; PMID: 23361061 |
| Colorectal cancer | CCN6 downregulation correlates with poor prognosis and increased invasiveness through modulation of TGF-β and Wnt pathways. | PMID: 24667642 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 0.0 | Not detected |
| Cartilage | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Mammary gland | 0.0 | Not detected |
| Placenta | 0.0 | Not detected |
| Small intestine | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Testis | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 0.0 | Low/undetectable in many breast cancer lines |
| MDA-MB-231 (breast cancer) | 0.0 | Low expression correlates with aggressive phenotype |
| HCT116 (colorectal cancer) | 0.0 | Reduced expression in invasive lines |
| HEK293 (embryonic kidney) | 0.0 | Used for recombinant expression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.156C>A (p.Cys52Ter) | Nonsense | Found in PPD patients | Loss of function; premature truncation |
| c.325G>A (p.Gly109Arg) | Missense | Found in PPD patients | Loss of function; impaired secretion |
| c.682C>T (p.Arg228Ter) | Nonsense | Found in PPD patients | Loss of function; premature truncation |
| c.1034G>A (p.Gly345Asp) | Missense | Found in PPD patients | Loss of function; disrupted protein folding |
Mutation functional classification
Loss of Function (LOF)
Most CCN6 mutations in progressive pseudorheumatoid dysplasia are loss-of-function, leading to truncated or misfolded protein with impaired secretion and signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CCN6.
Dominant Negative (DN)
No dominant-negative mutations have been described for CCN6.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• TGF-beta signaling pathway (KEGG: hsa04350)
• CCN family signaling (Reactome: R-HSA-3000171)
Protein Summary
CCN6 is a 354-amino acid secreted matricellular protein containing four conserved domains: IGFBP, VWC, TSP1, and CT. It modulates cell adhesion, migration, and proliferation through interactions with integrins and heparan sulfate proteoglycans. CCN6 is highly expressed in normal cartilage and bone, but its expression is frequently lost in cancers. The protein acts as a tumor suppressor by inhibiting Wnt/β-catenin signaling and maintaining epithelial phenotype.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCN6 Knockout HEK293 Cell Line | EDJ-KQ3345 | Human | 8838 | Details Get a Quote |
| CCN6 Knockout HeLa Cell Line | EDJ-KQ55017 | Human | 8838 | Details Get a Quote |
| CCN6 Knockout A-549 Cell Line | EDJ-KQ63500 | Human | 8838 | Details Get a Quote |
| CCN6 Knockout HCT 116 Cell Line | EDJ-KQ71968 | Human | 8838 | Details Get a Quote |
