HES3 and hypospadias: For hypospadias, also the molecular mechanism is complex, many genes are implicated (e.g., AR, ATF3, ATF3, BMP4, BMP7, BNC2, CTGF, CYP1A1, CYR61, DGKK, EGESR1, ESR2, FGF8, FGFR2, GSTM1, GSTT1, HOXA4, HOXB6, HSD17B3, HSD3B2, MAMLD1, MID1, SF1, SRD5A2, WT1 [28,38,59,71,72]; CYP11a1, CYP17a1, HES3, HSD3b1, INSL1, SF1, STAR, STAT3 [73], DGKK, STS, ZEB1 [27], EFNB2 [40], or NR5A1 [74]), genes that physiologically are involved in the development of the male external genitalia in an indifferent stage or in the hormone-dependent stage.