CCN2

Chr 6ADAR

cellular communication network factor 2

Also known as: CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2, SEMDLSL

NCBI Gene: 1490ENSG00000118523UniProt: P29279

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]

Primary Disease Associations & Inheritance

?Spondyloepimetaphyseal dysplasia, Li-Shao-Li typeMIM #621099
AD
Kyphomelic dysplasiaMIM #211350
AR
80
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CCN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 54 VUS of 80 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.06LOEUF
pLI 0.001
Z-score 1.42
OE 0.56 (0.32–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.52Z-score
OE missense 0.89 (0.78–1.01)
163 obs / 182.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.32–1.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.78–1.01)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 7 / 12.4Missense obs/exp: 163 / 182.8Syn Z: 0.98

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic3
VUS54
Likely Benign6
Benign1
16
Pathogenic
3
Likely Pathogenic
54
VUS
6
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
13
0
16
Likely Pathogenic
0
0
3
0
3
VUS
0
49
5
0
54
Likely Benign
0
3
1
2
6
Benign
0
0
1
0
1
Total15423280

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CCN2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spondyloepimetaphyseal dysplasia, Li-Shao-Li type

MIM #621099

Molecular basis of disorder known

Autosomal dominant

Kyphomelic dysplasia

MIM #211350

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.
Guo DZ et al.·Mol Cancer
2024
Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.
Livingston MJ et al.·Autophagy
2023
Cellular communication network factor 2 regulates smooth muscle cell transdifferentiation and lipid accumulation in atherosclerosis.
Xu Q et al.·Cardiovasc Res
2024
A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass.
Li S et al.·Bone Res
2024
Neutrophil-fibroblast crosstalk drives immunofibrosis in Crohn's disease through IFNα pathway.
Gavriilidis E et al.·Front Immunol
2024
Latest Progress of LIPUS in Fracture Healing: A Mini-Review.
Guo X et al.·J Ultrasound Med
2024Review
Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.
Tsilingiris D et al.·Eur J Immunol
2025
Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions.
Kubota S et al.·Clin Sci (Lond)
2015Review
Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment.
Neiens V et al.·Nat Commun
2025
Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis.
Larsen JH et al.·Cardiovasc Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PKM2 inhibitor suppresses kidney fibrogenesis by disrupting YAP-TEAD-CCN2 transcriptional signaling following ischemia-reperfusion injury.
Kosakai W et al.·J Biol Chem
2026🔓 Open Access
CCN2/CTGF-Driven Myocardial Fibrosis and NT-proBNP Synergy as Predictors of Mortality in Maintenance Hemodialysis.
Ko WC et al.·Int J Mol Sci
2025🔓 Open Access
Epidermal growth factor receptor promotes diabetic retinal fibrogenesis via YAP-CCN2-dependent manner.
Zhang W et al.·Exp Eye Res
2026
Study on the Mechanism of CCN2 Promoting Sorafenib Resistance in HCC and Its Combined Intervention Strategy.
Cui L et al.·Front Biosci (Landmark Ed)
2025Functional
Methionine restriction inhibits the TGF-β1/CCN2/NF-κB pathway to attenuate astrocyte inflammation and cognitive impairment in the APP/PS1 mice.
Liu H et al.·Int Immunopharmacol
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Pre-diabetes

Diet Impact on Hepatic Transcriptomics and Lipidomics in Pre-diabetes

ACTIVE NOT RECRUITING
NCT05965973Phase NALaval UniversityStarted 2023-06-09
Low fat dietHigh fat diet

External Resources

Links to major genomics databases and tools