Filaggrin

protein
Name=filaggrin
caption=


width=
HGNCid=3748
Symbol=FLG
AltSymbols=
EntrezGene=2312
OMIM=135940
RefSeq=NM_002016
UniProt=P20930
PDB=
ECnumber=
Chromosome=1
Arm=q
Band=21.3
LocusSupplementaryData=

Filaggrins are filament-associated proteins which bind to keratin fibers in epithelial cells.

Individuals with truncation mutations in the gene coding for filaggrin are stongly predisposed to a severe form of dry skin, (ichthyosis vulgaris), and/or eczema [cite journal |author=Weidinger S, Illig T, Baurecht H, "et al" |title=Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations |journal=J. Allergy Clin. Immunol. |volume=118 |issue=1 |pages=214–9 |year=2006 |pmid=16815158 |doi=10.1016/j.jaci.2006.05.004] .

Scientists hope to develop treatments for eczema through their newfound knowledge of filaggrin.

Truncation mutations R501X and 2284del4 are the most common mutations in the caucasian population, with 7-10% of the caucasian population carrying at least one copy of these mutations [cite journal |author=Palmer CN, Irvine AD, Terron-Kwiatkowski A, "et al" |title=Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis |journal=Nat. Genet. |volume=38 |issue=4 |pages=441–6 |year=2006 |pmid=16550169 |doi=10.1038/ng1767] .

It has been shown that almost 50% of all severe cases of eczema may have at least one mutated filaggrin gene.

R501X and 2284del4 are not generally found in non-caucasian individuals, though novel mutations (3321delA and S2554X) have been found in Japanese populations that yield similar effects. [cite journal |author=Nomura T, Sandilands A, Akiyama M, "et al" |title=Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis |journal=J. Allergy Clin. Immunol. |volume=119 |issue=2 |pages=434–40 |year=2007 |pmid=17291859 |doi=10.1016/j.jaci.2006.12.646]

Autoantibodies in rheumatoid arthritis recognizing an epitope of citrullinated peptides are cross-reactive with fillagrin. [cite journal |author=Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ |title=Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies |journal=J. Clin. Invest. |volume=101 |issue=1 |pages=273–81 |year=1998 |month=January |pmid=9421490 |doi=10.1172/JCI1316 |url=http://www.jci.org/articles/view/1316 PMC|508564]

The barrier defect seen in filaggrin null carriers also appears to lead to increased asthma susceptibility and exacerbations [cite journal |author=Basu K, Palmer CN, Lipworth BJ, Irwin McLean WH, Terron-Kwiatkowski A, Zhao Y, Liao H, Smith FJ, Mitra A, Mukhopadhyay S. |title=Filaggrin null mutations are associated with increased asthma exacerbations in children and young adults. |journal=Allergy |year=2008 |month=February | PMID: 18307574 |volume=E-Pub ahead of print] [cite journal |author=Palmer CN, Ismail T, Lee SP, Terron-Kwiatkowski A, Zhao Y, Liao H, Smith FJ, McLean WH, Mukhopadhyay S. |title=Filaggrin null mutations are associated with increased asthma severity in children and young adults |journal=J Allergy Clin Immunol |year=2007 |month=July |volume=120 |issue=1 |pages=64-68 |pmid=17531295] [Henderson J, Northstone K, Lee SP, Liao H, Zhao Y, Pembrey M, Mukhopadhyay S, Smith GD, Palmer CN, McLean WH, Irvine AD. The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study. J Allergy Clin Immunol. 2008 Apr;121(4):872-7.e9. Epub 2008 Mar 5. PMID: 18325573 ] and filaggrin deficiency is one of the top genome wide genetic determinants of asthma along with the variants found that regulate ORMDL3 expression [Tavendale R, Macgregor DF, Mukhopadhyay S, Palmer CN. A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. J Allergy Clin Immunol. 2008 Apr;121(4):860-3. PMID: 18395550] .

The penetrance of Filaggrin mutations may be increased by household exposure to cats [ Bisgaard H, Simpson A, Palmer CN, Bønnelykke K, McLean I, Mukhopadhyay S, Pipper CB, Halkjaer LB, Lipworth B, Hankinson J, Woodcock A, Custovic A. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med. 2008 Jun 24;5(6):e131. PMID: 18578563]

References

External links

* L J McKinley-Grant, W W Idler, I A Bernstein, D A Parry, L Cannizzaro, C M Croce, K Huebner, S R Lessin, and P M Steinert. [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=297512 Characterization of a cDNA clone encoding human filaggrin and localization of the gene to chromosome region 1q21.] "Proc Natl Acad Sci U S A". 1989 July; 86(13): 4848–4852.