Table 2. List of the 10 most differentially expressed (both up/downregulated) gene pathways.

Pathway name	Pathway identifier	#Entities found	#Entities total	Entities ratio	Entities pValue	Entities FDR	Genes
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)	R-HSA-2173791	3	19	0.00129	0.002827	0.43317	PARD3 ; RPS27A; F11R
Transcriptional regulation of pluripotent stem cells	R-HSA-452723	4	45	0.00306	0.004461	0.43317	NR5A1; EPAS1; ATP9A
RUNX1 regulates transcription of genes involved in BCR signaling	R-HSA-8939245	2	7	0.00048	0.004820	0.43317	BLK
CDC6 association with the ORC:origin complex	R-HSA-68689	2	11	0.00075	0.011458	0.43317	E2F2; E2F3
Signaling by NOTCH3	R-HSA-9012852	4	63	0.00428	0.014027	0.43317	PLEKHG1 ; PLXND1; RPS27A
Pexophagy	R-HSA-9664873	2	13	0.00088	0.015702	0.43317	EPAS1 ; RPS27A
NOTCH3 Intracellular Domain Regulates Transcription	R-HSA-9013508	3	36	0.00245	0.016072	0.43317	PLEKHG1 ; PLXND1
Erythrocytes take up oxygen and release carbon dioxide	R-HSA-1247673	2	16	0.00109	0.023123	0.43317	SLC4A1; HBD
Oncogene Induced Senescence	R-HSA-2559585	3	42	0.00285	0.023970	0.43317	E2F2; E2F3; RPS27A
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	R-HSA-9661069	2	17	0.00115	0.025859	0.43317	E2F2; E2F3

List of the top 10 human gene pathways that are most differentially expressed (both up/downregulated) from Reactome [13] overrepresentation analysis of significantly up/downregulated genes in six affected individuals compared with sex-matched controls and a log(fold change) >1.5 were used in gene set enrichment analysis of pathway and gene ontology. Pathways with an entities P value of <0.05 were considered significantly overrepresented. Genes in bold were upregulated, those in normal font were downregulated. FDR, false discovery rate is the probability corrected for multiple comparisons.