FBLN5 Gene

The FBLN5 gene (FBLN5 stands for "fibulin 5") is a protein-coding gene located on chromosome 14q32.12. The protein encoded by this gene, fibulin 5, is a secreted extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif and calcium-binding "epidermal-growth factor-like domain/EGF-like domains" (Papke CL et al. 2014). It promotes endothelial cell adhesion through interaction of integrins and the RGD motif. The encoded protein is expressed primarily in developing arteries but less so in adult vessels. However, it is again expressed more abundantly in balloon-injured vessels and atherosclerotic lesions, particularly in intimal vascular smooth muscle cells and endothelial cells. It is conceivable that the protein encoded by this gene plays a role in vascular development and remodeling.

Defects in the FBLN5 gene are a cause of autosomal dominant cutis laxa, autosomal recessive cutis laxa type I (CL type I), and age-related macular degeneration type 3 (ARMD3).

1. Scherrer DZ et al. (2013) Mutations in PYCR1 gene in three families with autosomal recessive cutis laxa, type 2. Eur J Med Genet 56:336-339.
2. de Vega S et al (2014) A C-terminal fragment of fibulin-7 interacts with endothelial cells and inhibits their tube formation in culture. Arch Biochem Biophys 545:148-153.
3. Kouwenberg D et al. (2011) Recognizable phenotype with common occurrence of microcephaly, psychomotor retardation, but no spontaneous bone fractures in autosomal recessive cutis laxa type IIB due to PYCR1 mutations.Am J Med Genet A 155A:2331-2332.
4. Loeys B et al (2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet 11:2113-2118.
5. Papke CL et al. (2015) Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.Hum Mol Genet 24:5867-5879.