FBN1 Gene: Fibrillin-1
Key extracellular matrix protein involved in Marfan syndrome and related connective tissue disorders
Gene Information Card
| Symbol | FBN1 |
|---|---|
| Full Name | Fibrillin-1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 |
| NCBI Gene ID | 2200 ncbi.nlm.nih.gov/gene/2200 |
| Ensembl ID | ENSG00000166147 |
| UniProt ID | P35555 |
| OMIM ID | 134797 |
| HGNC ID | 3603 |
| Aliases | FBN, MFS1, WMS, ACMICD, GPHYSD2, SSKS, ectopia lentis 1, isolated (EL1) |
Description
The FBN1 gene encodes fibrillin-1, a large glycoprotein that is a major component of extracellular microfibrils. These microfibrils provide structural support in connective tissues and regulate TGF-β signaling. Mutations in FBN1 cause Marfan syndrome and a spectrum of related disorders, including Weill-Marchesani syndrome, acromicric dysplasia, and stiff skin syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Marfan syndrome (MFS) | Dominant-negative or haploinsufficient fibrillin-1 disrupts microfibril assembly and leads to increased TGF-β signaling, causing aortic aneurysm, skeletal abnormalities, and ectopia lentis. | ClinVar, OMIM #154700 |
| Weill-Marchesani syndrome (WMS) | Missense mutations in FBN1 affecting TGF-β binding protein-like domain result in short stature, brachydactyly, and lens dislocation. | OMIM #277600, ClinVar |
| Acromicric dysplasia (ACMICD) | Dominant negative mutations in FBN1 cause severe short stature, stiff joints, and characteristic facial features. | OMIM #102370, ClinVar |
| Stiff skin syndrome (SSKS) | FBN1 mutations lead to thickened, hard skin due to abnormal microfibril deposition and TGF-β dysregulation. | OMIM #184900, ClinVar |
| Ectopia lentis, isolated (EL1) | Specific FBN1 mutations cause lens dislocation without systemic features of Marfan syndrome. | OMIM #129600, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 nTPM | Medium |
| Lung | 10.2 nTPM | Medium |
| Artery | 15.8 nTPM | Medium |
| Skin | 18.3 nTPM | Medium |
| Bone | 9.7 nTPM | Low |
| Eye | 14.1 nTPM | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Fibroblasts | 20.5 nTPM | High expression in dermal fibroblasts |
| Aortic smooth muscle cells | 16.2 nTPM | Key cell type for aortic wall integrity |
| Chondrocytes | 8.9 nTPM | Moderate expression in cartilage |
| Lens epithelial cells | 12.0 nTPM | Relevant to ectopia lentis |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1633C>T (p.Arg545Cys) | Missense | Common in Marfan syndrome | Dominant-negative effect on microfibril assembly |
| c.4777G>A (p.Gly1593Arg) | Missense | Associated with Weill-Marchesani syndrome | Alters TGF-β binding |
| c.7855C>T (p.Arg2619*) | Nonsense | Rare | Haploinsufficiency leading to Marfan syndrome |
| c.1874G>A (p.Gly625Asp) | Missense | Found in stiff skin syndrome | Gain-of-function? Increased microfibril deposition |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to haploinsufficiency cause Marfan syndrome by reducing fibrillin-1 levels.
Gain of Function (GOF)
Some missense mutations in stiff skin syndrome may lead to increased microfibril deposition, but evidence is limited.
Dominant Negative (DN)
Most Marfan syndrome mutations are dominant-negative, where mutant fibrillin-1 disrupts normal microfibril assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Extracellular matrix organization (Reactome R-HSA-1474244)
• TGF-beta signaling pathway (KEGG hsa04350)
• Elastic fibre formation (Reactome R-HSA-1566948)
Protein Summary
Fibrillin-1 is a 350 kDa glycoprotein composed of multiple calcium-binding EGF-like domains and TGF-β binding protein-like domains. It polymerizes to form microfibrils that provide elasticity and structural integrity to connective tissues. Fibrillin-1 also regulates TGF-β bioavailability by sequestering the latent complex. Mutations disrupt microfibril structure and TGF-β signaling, leading to a spectrum of connective tissue disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBN1 Knockout HEK293 Cell Line | EDJ-KQ376 | Human | 2200 | Details Get a Quote |
| FBN1 Knockout HeLa Cell Line | EDJ-KQ17981 | Human | 2200 | Details Get a Quote |
| FBN1 Knockout A-549 Cell Line | EDJ-KQ18581 | Human | 2200 | Details Get a Quote |
| FBN1 Knockout HCT 116 Cell Line | EDJ-KQ18582 | Human | 2200 | Details Get a Quote |
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