A number of de novo coding variants in the MYCBP2 gene, includiing three de novo loss-of-function (LoF) variants, have been identified in ASD probands from multiple cohorts (De Rubeis et al., 2014; Yuen et al., 2016; Yuen et al., 2017; Feliciano et al., 2019; Satterstrom et al., 2020; Zhou et al., 2022). AlAbdiet al., 2022 described a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy, and autism or autistic features who harbored de novo variants in the MYCBP2 gene; introduction of these disease-associated variants into conserved residues in the C. elegans MYCBP2 ortholog, RPM-1, demonstrated that C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioral abnormalities.
Molecular Function
This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
