FBN1 ( gene)

Location: Chromosome 15q21.1

GRCh38/hg38: 48,408,313 - 48,645,721. Reve

ENSEMBL transcript: ENST00000316623.10

Size: Very large gene (~230 kb of genomic DNA)

Exon number: 66

Canonical transcript: NM_000138.5 (~10.6 kb mRNA)

Coding sequence (CDS): 8616 nucleotides

Fibrilin-1 ( protein)

Size: Large extracellular glycoprotein (~350 kDa), 2871 amino acids.

Rich in calcium-binding epidermal growth factor-like (cbEGF) domains (43), important for stability and function. Contains transforming growth factor beta-binding protein-like (TB) domains, which regulate TGF-β activity. Modular organization supports flexibility and resistance to mechanical stress.

Localization: Secreted into the extracellular matrix (ECM).

Expression: Widely expressed, especially in connective tissue-rich organs (aorta, ligaments, ciliary zonules in the eye, skin).

Function: Main structural component of microfibrils, which provide scaffolding for elastic fibers. Critical for tissue elasticity and integrity, particularly in the aorta, ligaments, and ciliary zonules. Regulates growth factor signaling (notably TGF-β), linking structural and signaling roles.

Variants: Over 3,000 variants known, associated with connective tissue disorders, most notably Marfan syndrome, but also other fibrillinopathies (e.g., isolated ectopia lentis, MASS phenotype, stiff skin syndrome).