Fig. 5: The Wnt signaling pathway is promoted by Rnf146 overexpression.

a Volcano plot showing differentially expressed genes between Rnf146-overexpressing mice and eGFP-overexpressing mice (Rnf146-DEGs). The x-axis represents the log₂ scale of the fold change in differential expression, while the y-axis represents the -log₁₀ scale of the significance changes. Rnf146-DEGs associated with the Wnt signaling pathway are labeled in the plot. b Gene set enrichment plot depicting the elevated positive regulation of the Wnt signaling pathway in Rnf146-overexpressing mice. c Heatmap of the pathway activity for each sample inferred by PROGENy. The levels of pathway activity reflect the extent of pathway deregulation. d Enrichment analysis of the upregulated Rnf146-DEGs with pathway terms describing synaptic locations in the brain. Pathway analysis was performed using one-sided Fisher’s exact test to identify significantly overrepresented terms. The upregulated Rnf146-DEGs significantly overlapped (FDR < 0.01) with the integral component of the presynaptic membrane pathway (purple). Pathway terms with two or fewer overlapping genes were excluded and indicated as too few genes. e Enrichment analysis of Rnf146-DEGs with the inferred activity of transcription factors associated with ASD. Upregulated target genes of the transcription factor TCF4 are annotated in the plot. NES, normalized enrichment score. f Network of genes in WGCNA module 1 enriched in the Wnt signaling pathway and genes in module 2 enriched in synapse organization and memory. In each network, the top 30 hub genes (22 for memory) with the highest levels of intramodular connectivity were depicted. Rnf146-DEGs are highlighted in bold, with red and blue colors indicating up- and downregulation, respectively.