CCN3

cellular communication network factor 3, the group of Cellular communication network factors

Basic information

Region (hg38): 8:119416446-119424434

Previous symbols: [ "NOV" ]

Links

ENSG00000136999 ∙ NCBI:4856 ∙ OMIM:164958 ∙ HGNC:7885 ∙ Uniprot:P48745 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCN3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCN3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			11	1	1	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	11	1	1

Variants in CCN3

This is a list of pathogenic ClinVar variants found in the CCN3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-119416537-A-G		not specified	Uncertain significance (Nov 09, 2022)
8-119416552-C-A		not specified	Uncertain significance (Apr 16, 2024)
8-119416552-C-T		not specified	Likely benign (Jul 26, 2021)
8-119416576-G-T			Benign (Dec 31, 2019)
8-119416777-C-T		not specified	Uncertain significance (Nov 10, 2024)
8-119416798-C-T		not specified	Uncertain significance (Apr 22, 2022)
8-119416841-G-T		not specified	Uncertain significance (Dec 09, 2023)
8-119416844-C-T		not specified	Uncertain significance (Sep 01, 2024)
8-119416865-G-A		not specified	Uncertain significance (Oct 03, 2023)
8-119416913-G-A		not specified	Uncertain significance (May 26, 2022)
8-119416950-C-A		not specified	Conflicting classifications of pathogenicity (Sep 27, 2021)
8-119418079-T-A		not specified	Uncertain significance (Jun 06, 2023)
8-119418086-T-G		not specified	Uncertain significance (Aug 26, 2024)
8-119418175-G-A		not specified	Uncertain significance (Nov 10, 2024)
8-119418178-G-C		not specified	Uncertain significance (Nov 10, 2023)
8-119418192-C-G		not specified	Uncertain significance (Dec 13, 2023)
8-119418306-G-T		not specified	Uncertain significance (Jun 07, 2023)
8-119419173-C-G		Long QT syndrome	Likely benign (-)
8-119419235-G-A		not specified	Uncertain significance (May 29, 2024)
8-119419247-C-T		not specified	Uncertain significance (Dec 05, 2024)
8-119419265-C-T		not specified	Uncertain significance (Apr 04, 2024)
8-119422954-G-A		not specified	Uncertain significance (Aug 16, 2021)
8-119423011-G-A		not specified	Uncertain significance (Jul 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCN3	protein_coding	protein_coding	ENST00000259526	5	8048

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00664	0.977	125721	0	27	125748	0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.233	192	201	0.954	0.0000101	2313
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.000272	0.000272
South Asian	0.000360	0.000359
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.836
• hipred: Y
• hipred_score: 0.831
• ghis: 0.459

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ccn3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; limbs/digits/tail phenotype; muscle phenotype; vision/eye phenotype; craniofacial phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype