CCN1

Chr 1

cellular communication network factor 1

Also known as: CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10

The CCN1 protein is a secreted growth factor that promotes cell adhesion, proliferation, angiogenesis, and wound healing through interactions with integrins and regulation of genes involved in vascular development and tissue remodeling. Mutations cause autosomal dominant retinal arterial macroaneurysm with supravalvular pulmonic stenosis, a condition affecting both ocular and cardiac vascular systems. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.45), suggesting intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
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1
Active trials
66
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.45
LOEUF
DN
Mechanism· predicted
Clinical SummaryCCN1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.714
Z-score 3.18
OE 0.17 (0.080.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.37Z-score
OE missense 0.93 (0.831.04)
201 obs / 216.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.080.45)
00.351.4
Missense OE0.93 (0.831.04)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 3 / 17.2Missense obs/exp: 201 / 216.2Syn Z: 0.50
DN
0.6455th %ile
GOF
0.4678th %ile
LOF
0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

CCN1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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