Genetic mutations that disrupt any aspect of testis differentiation (SOX9, SRY, and many others), testosterone production (HSD3B, CYP17A1, and many others), AR binding of testosterone (SRD5A2 and AR), or androgen-responsive genes (FGF10, MAFB, and many others) consistently result in disrupted urethral closure and are often associated with severe hypospadias and differences in sex development in both human populations and mouse models [14]. This evidence concerns the gene AR and hypospadias.