CCN2

protein-coding

cellular communication network factor 2, the group of Cellular communication network factors

Gene summary

The protein encoded by this gene is a mitogen that is secreted by vascular endothelial cells. The encoded protein plays a role in chondrocyte proliferation and differentiation, cell adhesion in many cell types, and is related to platelet-derived growth factor. Certain polymorphisms in this gene have been linked with a higher incidence of systemic sclerosis. [provided by RefSeq, Nov 2009]

Previous symbols:

CTGF

MANE transcript

NM_001901.4

Inheritance

AR, AD

ClinVar variants

P:3U:50B:6

Top phenotype

Spondyloepimetaphyseal dysplasia, Li-Shao-Li type; Kyphomelic dysplasia

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr6:131,948,176-131,951,372

External References & Databases

Ensembl (ENSG00000118523)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

kyphomelic dysplasiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008881

Submitter: Ambry Genetics

spondyloepimetaphyseal dysplasiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100510

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spondyloepimetaphyseal dysplasia, Li-Shao-Li type; Kyphomelic dysplasiaAD/AR

Manifestation: Craniofacial; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 39414788; 39506047

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCN2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 9

Kyphomelic dysplasiaTotal: 2

Spondyloepimetaphyseal dysplasia, Li-Shao-Li typeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001901.4. 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				2 clinvar		2
missense	2 clinvar		50 clinvar	4 clinvar		56
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	3	0	50	6	0	59

Highest pathogenic variant AF is 6.84075e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001901.4	RefSeq	NP_001892.2	5	MANE Select
ENST00000367976.4	Ensembl	ENSP00000356954.3	5	MANE Select
ENST00000873798.1	Ensembl	ENSP00000543857.1	5	Standard
ENST00000918594.1	Ensembl	ENSP00000588653.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ccn2a	Danio rerio	Structure: myocardial precursor Quality: mislocalised laterally abnormal

Gene / Model

Organism

Observed Phenotype

ccn2a

Danio rerio

Structure: myocardial precursor

Quality: mislocalised laterally

abnormal

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367976
Coding exons: 5
Length: 3198
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.521	163	183	0.892	0.00000936	2255
Missense (PolyPhen)		49	69.949	0.70051		795
Synonymous	0.979	65	75.8	0.857	0.00000436	663
Loss of Function	1.42	7	12.4	0.564	7.20e-7	151

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes. Mediates heparin- and divalent cation-dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells. Enhances fibroblast growth factor-induced DNA synthesis. {ECO:0000269|PubMed:10614647, ECO:0000269|PubMed:12553878}.;

Recessive Scores

pRec: 0.861

Intolerance Scores

RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (gene trap): N