A de novo missense variant in the UNC13A gene (p.Pro814Leu) was identified in a 6-year-old diagnosed with ASD and comorbid ADHD and presenting with developmental delay and a dyskinetic movement disorder in Lipstein et al., 2017. Functional analysis in murine neuronal cultures and C. elegans demonstrated that this variant resulted in a gain-of-function effect characterized by increased fusion propensity of synaptic vesicles, leading to increased initial synaptic vesicle release probability and abnormal short-term synaptic plasticity.
Molecular Function
Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Also involved in secretory granule priming in insulin secretion.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder.
