Relevance to Autism

A de novo missense variant in the NEDD4 gene was identified in a male ASD proband born to non-consanguineous Pakistani parents (Khan et al., 2024). De novo variants in this gene, including a de novo missense variant, have also been identified in ASD probands from the SPARK cohort (Zhou et al., 2022). A paternally-inherited loss-of-function variant in NEDD4 was identified in one of two ASD-affected siblings in a multiplex family from the AGRE cohort (Cirnigliaro et al., 2023).

Molecular Function

This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. Regulation of Rap2A by the ubiquitin ligase NEDD4 was found to control neurite development in mice (Kawabe et al., 2010).

External Links

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