We performed pathway enrichment analysis of the Tier 1 genes in SynGO. From Tier 1, 11 genes mapped to the set of SynGO annotated genes (CACNA1E, DCC, EFNA5, GRIA1, GRM8, LRFN5, MDGA2, NCAM1, OLFM1, PCLO, and SORCS3). Relative to other brain-expressed genes, Tier 1 genes were significantly overrepresented in the synapse (P = 0.0009, qFDR = 0.003), pre- and post-synapse (P = 0.0086, qFDR = 0.0086 and P = 0.003, qFDR = 0.004, respectively), and four subcategories (Extended Data Fig. 6). By contrast, there was no significant overrepresentation of genes when we applied this test to the entire set of 415 protein coding genes. Other notable Tier 1 genes included PDE4B related to synaptic function and TNF-related immune-regulatory genes, including TANK and TRAF3.
