CCN3
protein-codingcellular communication network factor 3, the group of Cellular communication network factors
Gene summary
The protein encoded by this gene is a small secreted cysteine-rich protein and a member of the CCN family of regulatory proteins. CNN family proteins associate with the extracellular matrix and play an important role in cardiovascular and skeletal development, fibrosis and cancer development. [provided by RefSeq, Feb 2009]
- NOV
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCN3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002514.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 41 | 3 | 1 | 45 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 4 | 1 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002505.1 | 5 | MANE Select | |
| Ensembl | ENSP00000259526.3 | 5 | MANE Select | |
| Ensembl | ENSP00000535042.1 | 5 | Standard | |
| Ensembl | ENSP00000535042.1 | 5 | Standard |
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000259526
- Coding exons
- 5
- Length
- 8048
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125748
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.233 | 192 | 201 | 0.954 | 0.0000101 | 2313 |
| Missense (PolyPhen) | 68 | 89.592 | 0.75899 | 1005 | ||
| Synonymous | -0.378 | 80 | 75.8 | 1.06 | 0.00000341 | 692 |
| Loss of Function | 2.10 | 6 | 14.7 | 0.409 | 6.27e-7 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival (PubMed:15181016, PubMed:15611078, PubMed:12695522, PubMed:21344378, PubMed:12050162). Acts by binding to integrins or membrane receptors such as NOTCH1 (PubMed:12695522, PubMed:21344378, PubMed:15611078). Essential regulator of hematopoietic stem and progenitor cell function (PubMed:17463287). Inhibits myogenic differentiation through the activation of Notch-signaling pathway (PubMed:12050162). Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling (PubMed:20139355). Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival (PubMed:12695522). Plays also a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (PubMed:15611078). Involved in bone regeneration as a negative regulator (By similarity). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (PubMed:21871891). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (By similarity). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti- inflammatory effects occur secondary to the inhibition of NF- kappaB signaling pathway (PubMed:21063504). Contributes to the control and coordination of inflammatory processes in atherosclerosis (By similarity). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (PubMed:21871891). {ECO:0000250|UniProtKB:Q64299, ECO:0000269|PubMed:12050162, ECO:0000269|PubMed:12695522, ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15611078, ECO:0000269|PubMed:17463287, ECO:0000269|PubMed:20139355, ECO:0000269|PubMed:21063504, ECO:0000269|PubMed:21344378, ECO:0000269|PubMed:21871891}.;
Recessive Scores
- pRec
- 0.180
Intolerance Scores
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63
Essentials
- Essential (gene trap)
- N