FBLN2
Chr 3fibulin 2
The protein encodes fibulin-2, an extracellular matrix protein that binds fibronectin and other ligands in a calcium-dependent manner and mediates interactions between fibrillin-1 and elastin. Mutations cause syndromic thoracic aortic aneurysms and dissections with skeletal abnormalities following autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, suggesting such mutations are likely pathogenic when they occur.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
288 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 229 | 2 | 0 | 231 |
Likely Benign | 0 | 6 | 0 | 3 | 9 |
Benign | 0 | 3 | 0 | 5 | 8 |
| Total | 0 | 238 | 24 | 8 | 270 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FBLN2 · 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