A de novo missense variant in the HACE1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; functional assessment of this variant by a high throughput Massively Parallel Splicing Assay (MaPSY) in Rhine et al., 2022 demonstrated that this variant disrupted splicing, and this functional effect was further validated by RT-PCR. A de novo in-frame deletion variant and multiple rare de novo non-coding variants in HACE1 have also been observed in ASD probands (Krumm et al., 2015; Yuen et al., 2017;Turner et al., 2017).
Molecular Function
This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. Biallelic variants in HACE1 are responsible for spastic paraplegia and psychomotor retardation with or without seizures (SPPRS; OMIM 616756), an autosomal recessive complex neurodevelopmental disorder with onset in infancy in which affected children show hypotonia followed by severely impaired global development and significant motor disability (Hollstein et al., 2015; Akawi et al., 2015).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
