CCN3
Chr 8cellular communication network factor 3
Also known as: IBP-9, IGFBP-9, IGFBP9, NOV, NOVh
CCN3 encodes a secreted cysteine-rich protein that regulates cellular processes including proliferation, differentiation, and survival by binding to integrins and membrane receptors, and plays essential roles in hematopoietic stem cell function, angiogenesis, and bone development. Mutations in CCN3 cause autosomal dominant elbow-knee synostosis, a skeletal malformation syndrome affecting joint development. The gene shows low constraint to loss-of-function variants, suggesting tolerance to such mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CCN3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools