FBXL5

The protein functions as a component of SCF ubiquitin ligase complexes that regulate iron homeostasis by promoting degradation of iron regulatory proteins, particularly under conditions of iron sufficiency and oxidative stress. Mutations in this highly constrained gene cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and seizures. The gene shows extreme intolerance to loss-of-function variants, indicating that even partial loss of protein function can have significant clinical consequences.