WDFY3

Gene product: Autophagy-Linked FYVE Protein.

Protein function: WDFY3 can degrade misfolded ubiquitinated proteins through autophagy by interacting with p62 protein. In addition, it can regulate Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner[1-2].

Phenotype: Microcephaly 18, primary, autosomal dominant? (AD) (it can be manifested as mild to moderate neurodevelopmental delay, intellectual disability, microcephaly or macrocephaly (it is considered that haploinsufficiency may be related to macrocephaly, while the variation in PH domain is related to microcephaly), autism spectrum disorders, attention deficit hyperactivity disorder and other abnormalities [2-3]. In addition, HPO database records that the gene is associated with the phenotype of seizure, but I have not found the revelant case reports at present).

Mutation database: ClinVar.

Clinical and basic research: PubMed (PMID: 34187232 (J Cereb Blood Flow Metab. 2021), 31327001 (Brain. 2019)).

References:

1. Clausen, T.H., et al., p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy, 2010. 6(3): p. 330-44.
2. Kadir, R., et al., ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size. PLoS Genet, 2016. 12(3): p. e1005919.
3. Le Duc, D., et al., Pathogenic WDFY3 variants cause neurodevelopmental disorders and opposing effects on brain size. Brain, 2019. 142(9): p. 2617-2630.