FBXW11

This gene encodes a substrate recognition component of the SCF ubiquitin ligase complex that targets phosphorylated proteins for degradation, regulating critical pathways including Wnt signaling, NF-kappa-B activation, circadian rhythms, and mTORC1 signaling. Mutations cause a neurodevelopmental disorder with intellectual disability, developmental delay, seizures, and behavioral abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), indicating that haploinsufficiency is likely not tolerated in the general population.