Alternatively, rare variants in DENND1A, a gene encoding a 1009 amino acid protein with a clathrin-binding domain regulating endosome-mediated endocytosis, receptor cycling and calcium-dependent signaling cascades [44,45], also have been associated with endocrine-metabolic traits in families of daughters with PCOS [46]. This evidence concerns the gene DENND1A and polycystic ovary syndrome.