CLCN3, SNAP91, and TSNARE1 are direct synaptic components, and CNTN4 and FURIN play roles in neurodevelopment. Specifically, CLCN3 (or ClC-3) is a brain-expressed chloride channel, where it appears to control fast excitatory glutamatergic transmission 27. SNAP91 is enriched in the presynaptic terminal of neurons where it regulates clathrin-coated vesicles, the major means of vesicle recycling at the presynaptic membrane. TSNARE1 plays key roles in docking, priming, and fusion of synaptic vesicles with the presynaptic membrane in neurons, thus synchronizing neurotransmitter release into the synaptic cleft. CNTN4 is a member of the contactin extracellular cell matrix protein family responsible for development of neurons including network plasticity28. It plays a key role in olfactory axon guidance29, and there is evidence for association of copy number variants overlapping CNTN4 with autism30. FURIN processes precursor proteins to mature forms, including brain-derived neurotrophic factor (BDNF), a key molecule in brain development whose down-modulation has been hypothesized as related to schizophrenia31, and BDNF and FURIN are up-regulated in astrocytes in response to stress.
