FLG Gene: Filaggrin Function, Mutations, and Associated Diseases

The FLG gene encodes filaggrin, a filament-associated protein that aggregates keratin intermediate filaments in the stratum corneum of the epidermis. It is synthesized as a large precursor, profilaggrin, which is proteolytically processed into multiple filaggrin repeats. Filaggrin is essential for skin barrier formation and hydration; its breakdown products contribute to natural moisturizing factor. Loss-of-function mutations in FLG are a major risk factor for atopic dermatitis, ichthyosis vulgaris, and associated allergic conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Keratinization (Reactome: R-HSA-6805567)

• Formation of the cornified envelope (Reactome: R-HSA-6809371)

• Developmental biology (Reactome: R-HSA-1266738)

Filaggrin is a 406 kDa precursor protein (profilaggrin) consisting of multiple filaggrin repeats flanked by N- and C-terminal domains. After dephosphorylation and proteolysis, mature filaggrin binds keratin intermediate filaments, promoting their aggregation into macrofibrils. In the upper stratum corneum, filaggrin is further degraded into amino acids and derivatives that constitute natural moisturizing factor, crucial for skin hydration and pH regulation. Loss of filaggrin leads to dry, scaly skin and increased permeability to allergens.