Taken together, we uncovered a comprehensive mechanism of hub genes involved in HF, which was a compact regulatory interaction of TFs–hub genes–pathways: The up-regulations of TFs (BNC2 and MEOX2) activate the transcriptions of four hub genes (COL14A1, OGN, MFAP4, SFRP4) and subsequently drive the activation or suppression of downstream signaling pathways (Figure 11). The gene discussed is SFRP4; the disease is hydrops fetalis.