CCN6 Gene

Name cellular communication network factor 6
Description 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 is overexpressed in colon tumors. It may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Mutations of this gene are associated with progressive pseudorheumatoid dysplasia, an autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCN6 (also known as WISP3) is a secreted extracellular matrix–associated protein that plays a critical tumor‐suppressive role in the breast and modulates key signaling pathways involved in cell differentiation and invasion. In inflammatory breast cancer, reduced CCN6 expression is associated with a loss of epithelial characteristics, enhanced epithelial‐to‐mesenchymal transition, and increased invasive behavior. Several studies demonstrate that restoration of CCN6 activity limits breast cancer invasion by antagonizing pathways such as the BMP4–TAK1–p38 axis, thereby reducing metastatic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, CCN6 attenuates insulin‐like growth factor–1 signaling and its downstream activators (including transcription factors such as ZEB1 and Snail), which helps maintain E‐cadherin expression and a differentiated epithelial phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In addition to its role in breast cancer, loss‐of‐function mutations in CCN6/WISP3 are responsible for progressive pseudorheumatoid dysplasia in humans, highlighting its importance in cartilage homeostasis, although mutant mouse models do not recapitulate the human skeletal phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Taken together, these findings establish CCN6 as a pivotal modulator of growth factor signaling, cell adhesion, and differentiation; its loss disrupts these regulatory circuits and contributes to enhanced tumor aggressiveness and metastatic behavior.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anupama Pal, Wei Huang, Xin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCN6 modulates BMP signaling via the Smad-independent TAK1/p38 pathway, acting to suppress metastasis of breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-0154"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-0154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22805309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22805309"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Celina G Kleer, Yanhong Zhang, Quintin Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "WISP3 is a novel tumor suppressor gene of inflammatory breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1205462"}], "href": "https://doi.org/10.1038/sj.onc.1205462"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12082632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12082632"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guadalupe Lorenzatti, Wei Huang, Anupama Pal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CCN6 (WISP3) decreases ZEB1-mediated EMT and invasion by attenuation of IGF-1 receptor signaling in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.084194"}], "href": "https://doi.org/10.1242/jcs.084194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21525039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21525039"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Wei Huang, Yanhong Zhang, Sooryanarayana Varambally, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of CCN6 (Wnt-1-induced signaling protein 3) down-regulates E-cadherin in the breast epithelium through induction of snail and ZEB1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2008.070899"}], "href": "https://doi.org/10.2353/ajpath.2008.070899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18321996"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18321996"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yanhong Zhang, Quintin Pan, Hui Zhong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/bcr1351"}], "href": "https://doi.org/10.1186/bcr1351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16457688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16457688"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Wendy E Kutz, Yaoqin Gong, Matthew L Warman "}, {"type": "b", "children": [{"type": "t", "text": "WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.1.414-421.2005"}], "href": "https://doi.org/10.1128/MCB.25.1.414-421.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15601861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15601861"}]}]}]}
NCBI Gene ID 8838
API
Download Associations
Predicted Functions View CCN6's ARCHS4 Predicted Functions.
Co-expressed Genes View CCN6's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CCN6's ARCHS4 Predicted Functions.

Functional Associations

CCN6 has 1,539 functional associations with biological entities spanning 6 categories (chemical, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 21 datasets.

Click the + buttons to view associations for CCN6 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CCN6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of CCN6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
ClinVar Gene-Phenotype Associations 2025 phenotypes associated with CCN6 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
CM4AI KOLF21J CRISPRi Gene Perturbation Atlas gene perturbations changing expression of CCN6 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CCN6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CCN6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving CCN6 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CCN6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
GO Biological Process Annotations 2025 biological processes involving CCN6 gene from the curated GO Biological Process Annotations2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of CCN6 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CCN6 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with CCN6 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CCN6 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Mouse Transcription Factor Targets 2025 transcription factors regulating expression of CCN6 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of CCN6 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
PFOCR Pathway Figure Associations 2024 pathways involving CCN6 protein from the Wikipathways PFOCR 2024 dataset.
Rummagene Transcription Factor Associations 2026 transcription factors regulating expression of CCN6 gene from the Rummagene Transcription Factor Associations 2026 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CCN6 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CCN6 gene from the RummaGEO Gene Perturbation Signatures dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CCN6 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CCN6 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.