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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CCN1
cellular communication network factor 1
Chromosome 1 · 1p22.3
NCBI Gene: 3491Ensembl: ENSG00000142871.19HGNC: HGNC:2654UniProt: O00622
333PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of BMP signaling pathwaypositive regulation of osteoblast proliferationprotein bindingpositive regulation of osteoblast differentiationAbnormality of the skeletal systemvein disorderlymphatic system diseaseglomerulonephritis
✦AI Summary

CCN1 (cellular communication network factor 1) is a matricellular protein that regulates diverse cellular processes including proliferation, migration, angiogenesis, and tissue repair 1. The protein functions through binding to multiple integrin receptors and activating various signaling pathways, including FAK/STAT3, AKT, and NF-κB pathways 23. CCN1 promotes wound healing by enhancing angiogenesis and upregulating genes involved in matrix remodeling and inflammation 3. Recent studies have identified novel cellular roles for CCN1, including regulation of ferroptosis through mitochondrial fatty acid β-oxidation via interaction with ETFA 4, and involvement in RNA splicing regulation 5. In disease contexts, CCN1 expression is associated with cancer progression and poor prognosis in multiple malignancies 62. In glioblastoma, CCN1 promotes mesenchymal phenotype transition in glioma stem cells through S100A8-mediated NF-κB activation 2. CCN1 also plays critical roles in various pulmonary diseases including acute lung injury, COPD, lung fibrosis, and lung cancer 1. The protein's diverse and sometimes contradictory functions arise from its ability to bind different receptors and activate distinct signaling pathways in various cellular contexts 7.

Sources cited
1
CCN1 regulates proliferation, differentiation, apoptosis, angiogenesis, and fibrosis, with roles in pulmonary diseases
PMID: 33105556
2
CCN1 promotes mesenchymal phenotype transition in glioma stem cells through FAK/STAT3 and S100A8/NF-κB pathways
PMID: 39659236
3
CCN1 enhances wound healing and angiogenesis through AKT signaling pathway activation
PMID: 36541685
4
CCN1 drives ferroptosis via mitochondrial fatty acid β-oxidation through ETFA interaction
PMID: 40280135
5
CCN1 is involved in RNA splicing regulation and associated with glioblastoma progression
PMID: 35910786
6
CCN1/CYR61+ cells identified as relapse-initiators in epithelial ovarian cancer
PMID: 34992217
7
CCN1's diverse functions arise from binding different receptors and activating various signaling pathways
PMID: 40286773
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.55Moderate
vein disorderOpen Targets
0.33Weak
lymphatic system diseaseOpen Targets
0.33Weak
glomerulonephritisOpen Targets
0.26Weak
chronic fatigue syndromeOpen Targets
0.26Weak
eosinophilic esophagitisOpen Targets
0.17Weak
neoplasmOpen Targets
0.12Weak
rheumatoid arthritisOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
esophageal squamous cell carcinomaOpen Targets
0.10Weak
osteosarcomaOpen Targets
0.10Weak
glioblastoma multiformeOpen Targets
0.10Weak
melanomaOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Suggestive
psoriasisOpen Targets
0.10Suggestive
esophageal adenocarcinomaOpen Targets
0.10Suggestive
non-small cell lung carcinomaOpen Targets
0.10Suggestive
acute lymphoblastic leukemiaOpen Targets
0.10Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOSProtein interaction100%TEAD1Protein interaction84%CCN2Protein interaction78%IGFBP7Protein interaction78%SPARCProtein interaction78%ATF3Protein interaction77%
Tissue Expression6 tissues
Lung
100%
Liver
65%
Ovary
27%
Heart
25%
Brain
7%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
CCN1FOSTEAD1CCN2IGFBP7SPARCATF3
PROTEIN STRUCTURE
Preparing viewer…
PDB4D0Z · 2.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.31 [0.20–0.51]
RankingsWhere CCN1 stands among ~20K protein-coding genes
  • #975of 20,598
    Most Researched333 · top 5%
  • #3,095of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedCCN1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Targeting the splicing factor NONO inhibits GBM progression through GPX1 intron retention.
PMID: 35910786
Theranostics · 2022
1.00
2
Mitochondrial CCN1 drives ferroptosis via fatty acid β-oxidation.
PMID: 40280135
Dev Cell · 2025
0.90
3
C-terminal binding protein-2 triggers CYR61-induced metastatic dissemination of osteosarcoma in a non-hypoxic microenvironment.
PMID: 40038783
J Exp Clin Cancer Res · 2025
0.84
4
Nanomechanics of CCN1-Mediated
PMID: 38959438
Nano Lett · 2024
0.80
5
Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review.
PMID: 25660807
Gerontology · 2015
0.80