For the blue “neuronal differentiation” module, canonical pathway annotation was enriched in axon guidance and generic transcription pathways (Tables S5, S6). The axon guidance genes, all upregulated in probands, included members of the neural cell adhesion family (NCAM1, NRCAM, L1CAM, NFASC), semaphorin (PLXNC1, PLXNB3), netrin (DCC, UNC5A), Rho GTPases (PAK3, PAK7), CDK5R1/P35, and DCX. Many of these molecules were among the top 100 hub genes, i.e., CDK5R1, DPYSL5, DCX, DPF1, APC2 (Figure 2C; Table S7). Hence, genes in the blue module are involved in cytoskeletal regulation of various cellular functions, including neurite outgrowth, axon guidance, cell proliferation, migration, and survival.
