Fig. 3

Ingenuity pathway analysis of enriched autism genes under CNVs. The major hubs in the pathway included the genes CACNA1, DPP6, CHRNA7, GABRG3, and NIPA1. This pathway was built from a list of prevalent 25 causal genes in study populations. This pathway has been divided into seven sub-pathways: 1) 4 clusters of CACNA1 genes consisting of CACNA1H, CACNA1C, CACNA1B, and CACNA1I calcium channel signalling. 2) DPP6 is a single-pass type II membrane protein and a member of the peptidase S9B family of serine proteases. It is involved in the physiological processes of brain function and may modulate the cell surface expression and the activity of the potassium channel KCND2. 3) DLG1 is a multi-domain scaffolding protein, which is required for healthy development. It has a role in septate junction formation, signal transduction, cell proliferation, synaptogenesis, and lymphocyte activation. 4) UBE3A functions, both as an E3 ligase in the ubiquitin-proteasome pathway and as a transcriptional co-activator. 5) CHRNA7 belongs to ligand-gated ion channels mediating fast signal transmission at synapses. The protein encoded by the gene forms a homo-oligomeric channel and displays marked permeability to calcium ions. 6) GABRG3 is the major inhibitory neurotransmitter in the vertebrate brain. It mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor, leading to opening an integral chloride channel. This protein is a gamma subunit, which contains the benzodiazepine binding site. GABRG3 is strongly implicated in autism pathogenesis. It is involved in the inhibition of excitatory neural pathways and expression in early development. 7) NIPA1 encodes magnesium transporter associated with early endosomes and the cell surface in different neuronal and epithelial cells. This protein plays a role in development and maintenance in the nervous system