FBN2 Gene - Fibrillin 2
Genetic and clinical significance of FBN2 in connective tissue disorders
Gene Information Card
| Symbol | FBN2 |
|---|---|
| Full Name | Fibrillin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q23.3 |
| NCBI Gene ID | 2201 ncbi.nlm.nih.gov/gene/2201 |
| Ensembl ID | ENSG00000138829 |
| UniProt ID | P35556 |
| OMIM ID | 121050 |
| HGNC ID | 3604 |
| Aliases | CCA, DA9, MFS2, FBNL, MASS, MFS2-like |
Description
FBN2 encodes fibrillin-2, a large extracellular matrix glycoprotein that is a major component of microfibrils. These microfibrils provide structural support in connective tissues and regulate TGF-β signaling. Mutations in FBN2 cause congenital contractural arachnodactyly (Beals syndrome), a disorder characterized by joint contractures, arachnodactyly, and scoliosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital contractural arachnodactyly (Beals syndrome) | Missense or splice-site mutations in FBN2 disrupt microfibril assembly and TGF-β sequestration, leading to connective tissue fragility and abnormal joint development. | ClinVar, OMIM |
| Marfan syndrome (atypical) | Rare FBN2 mutations have been reported in patients with Marfan-like features, though classic Marfan is primarily linked to FBN1. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Heart | 8.3 | Low |
| Skeletal muscle | 6.7 | Low |
| Skin | 15.2 | Medium |
| Aorta | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Fibroblasts (skin) | 22.1 | High expression in dermal fibroblasts |
| Aortic smooth muscle cells | 14.3 | Moderate expression |
| Lung epithelial cells (A549) | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.266G>A (p.Cys89Tyr) | Missense | Rare | Disrupts disulfide bond in EGF-like domain, impairing microfibril assembly |
| c.3463G>T (p.Gly1155Cys) | Missense | Rare | Alters calcium-binding EGF domain, leading to dominant-negative effect |
| c.4777-2A>G | Splice site | Rare | Exon skipping, frameshift, and premature truncation |
Mutation functional classification
Loss of Function (LOF)
Rare; nonsense or frameshift mutations leading to haploinsufficiency may contribute to mild phenotypes.
Gain of Function (GOF)
Not well documented for FBN2; most mutations are dominant-negative.
Dominant Negative (DN)
Common mechanism; missense mutations in EGF-like domains produce abnormal fibrillin-2 that disrupts microfibril formation.
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix structural constituent (GO:0005201) | • protein binding (GO:0005515) |
| • extracellular matrix constituent conferring elasticity (GO:0030023) | • extracellular region (GO:0005576) |
| • extracellular space (GO:0005615) | • cell adhesion (GO:0007155) |
| • extracellular matrix organization (GO:0030198) | • collagen-containing extracellular matrix (GO:0062023) |
Pathways
• ECM-receptor interaction (KEGG hsa04512)
• Focal adhesion (KEGG hsa04510)
• TGF-beta signaling pathway (KEGG hsa04350)
• Microfibril assembly (Reactome R-HSA-216083)
Protein Summary
Fibrillin-2 is a 2912-amino acid glycoprotein with multiple calcium-binding EGF-like domains and TGF-β-binding protein-like domains. It assembles into microfibrils that provide tensile strength and elasticity in connective tissues. Fibrillin-2 also sequesters latent TGF-β complexes, regulating growth factor availability. Mutations in FBN2 primarily cause dominant-negative disruption of microfibril structure, leading to congenital contractural arachnodactyly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBN2 Knockout HEK293 Cell Line | EDJ-KQ2572 | Human | 2201 | Details Get a Quote |
| FBN2 Knockout A-549 Cell Line | EDJ-KQ23253 | Human | 2201 | Details Get a Quote |
| FBN2 Knockout HeLa Cell Line | EDJ-KQ23254 | Human | 2201 | Details Get a Quote |
| FBN2 Knockout HCT 116 Cell Line | EDJ-KQ70166 | Human | 2201 | Details Get a Quote |
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