FBN1
Chr 15ADfibrillin 1
Also known as: ACMICD, ECTOL1, FBN, GPHYSD2, MASS, MFLS, MFS1, OCTD
The protein fibrillin-1 forms calcium-binding microfibrils that provide structural support in elastic and nonelastic connective tissue throughout the body, while the co-encoded hormone asprosin regulates glucose homeostasis. Mutations cause autosomal dominant connective tissue disorders including Marfan syndrome, MASS syndrome, ectopia lentis, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome, and several other related conditions. The pathogenic mechanism involves loss of function, leading to compromised structural integrity of connective tissues.
Definitive — sufficient evidence for diagnostic panels
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FBN1 · 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
The LD Lync Study - Natural History Study of Lipodystrophy Syndromes
RECRUITINGTranscriptomic Study of Adult Population With Marfan Syndrome
RECRUITINGGenetic Architecture of Acute Aortic Syndromes and Aortic Aneurysm.
RECRUITINGFibroblasts and Thoracic Aortic Aneurysms: in Vitro Characterization in With Marfan Syndrome and Genetic Aortic Diseases
ENROLLING BY INVITATIONPathogenetic Basis of Aortopathy and Aortic Valve Disease
ACTIVE NOT RECRUITINGScATtEred Rare Disease Biobanks: a Model of Sample/Data Collection With susTainablE and Shared Criteria
RECRUITINGNational Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil's Unified Health System Through a Multicenter Registry
RECRUITINGExternal Resources
Links to major genomics databases and tools