Table 1.

Known Synaptotagmin Isoforms, Dysfunctions, and Clinical Mutations. Known synaptotagmin isoforms of clinical and functional relevance related to SYT1-associated neurodevelopmental disorder, including their noted neurotransmitter mechanism of release and related molecular dysfunction.

Isoform	Location	NT Mechanism of Release	Molecular Dysfunction	Clinical Symptoms of Mutation
SYT1	Synaptic vesicles and secretory granules of neuroendocrine of the hippocampus and forebrain	Independent fast synchronous NT release, clamping mini spontaneous release	Decreased evoked transmission	Developmental delay, sleep disturbances, EEG abnormalities, abnormal motor function, abnormal eye physiology
SYT2	Inhibitory neurons of the brainstem, spinal cord, cerebellum, and striatal neurons, neuromuscular junction	Evoked fast synchronous NT release	Impaired NT vesicle release	Moderate to severe motor deficits, muscle weakness, bulbar deficits, delayed motor development
SYT7	Hippocampus	SV priming and clamping, slow asynchronous NT release	Decrease RRP when KO alongside SYT1,	Mania, behavioral disturbances, bipolar-like behavior (in mice)
SYT9	Dense core vesicles and synaptic vesicles in limbic system and striatum, cortical and hippocampal neurons	Evoked fast synchronous NT release	Decrease in spontaneous miniature rate of synaptic vesicle fusion, inability to initiate membrane fusion	Not Available