Two de novo variants in the HECTD4 gene (one nonsense, one missense) were identified in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. Yuen et al., 2017 identified additional HECTD4 loss-of-function variants by whole genome sequencing in three ASD families. Despite being a mutation-intolerant gene with a pLI score of 1.00, HECTD4 did not meet the statistical significance criteria used in Yuen et al., 2017 to be designated as an ASD candidate gene, which was a higher-than-expected mutation rate (false discovery rate < 15%).
Molecular Function
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome
