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Filaggrin ( filament aggregating prote in; FLG) is a filament-associated protein that binds to keratin fibers in Epithelium. Ten to twelve filaggrin units are post-translationally hydrolyzed from a large profilaggrin precursor protein during terminal differentiation of epidermal cells. In humans, profilaggrin is encoded by the FLG gene, which is part of the S100 fused-type protein (SFTP) family within the epidermal differentiation complex on chromosome 1q21. In Cetacea and Sirenia, the FLG family has lost its function, with the curious exception of Manatee in the latter clade: manatees still retain some functional FLG genes.
Some studies attribute an important role to filaggrin in maintaining the physiological acidic pH of the skin, through a breaking-down mechanism to form histidine and subsequently trans-urocanic acid. However, others have shown that the filaggrin–histidine–urocanic acid cascade is not essential for skin acidification.
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) that yield similar effects have been found in Japanese populations. Truncation mutations R501X and 2284del4 are the most common mutations in the Caucasian race population, with 7 to 10% of the Caucasian population carrying at least one copy of these mutations.
Autoantibodies in rheumatoid arthritis recognizing an epitope of citrullinated peptides are cross-reactive with filaggrin.
The barrier defect seen in filaggrin null carriers also appears to lead to increased asthma susceptibility and exacerbations. Filaggrin deficiency is one of the top genome-wide genetic determinants of asthma, along with the variants found that regulate ORMDL3 expression.
In early infancy, the penetrance of filaggrin mutations may be increased by household exposure to cats.
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