WD repeat and FYVE domain-containing protein 3 (WDFY3)

WD repeat and FYVE domain-containing protein 3 (WDFY3) is a large scaffolding and adaptor protein containing WD40 repeats, a BEACH domain, and a C-terminal FYVE domain. It functions as a master adaptor for the selective clearance of protein aggregates (aggrephagy) via the autophagy pathway. WDFY3 interacts with components of the autophagic machinery (such as ATG5, ATG12, ATG16L, SQSTM1/p62, and LC3), linking ubiquitinated cargo and aggregated proteins to autophagic vesicles for degradation. It participates in axonal tract formation throughout the brain and spinal cord, is crucial for proper neuron differentiation and migration, and is involved in mitochondrial homeostasis, including mitophagy and energy regulation in neurons. Mutations in WDFY3 are linked to macrocephaly, intellectual disability, autism spectrum disorders, and other neurodevelopmental phenotypes. There is currently no evidence that WDFY3 is a direct drug target, though its pathway is implicated in disease mechanisms for several neurological and psychiatric disorders.

Other names

ALFYZFYVE25BCHSMCPH18WD repeat and FYVE domain containing 3WDFY3