DENND1A and obesity due to melanocortin 4 receptor deficiency: This suggests that DENND1A.V2 is part of a novel signal transduction network including genes on 12q13 engaged in vesicular trafficking [20] of cell surface receptors for gonadotropins and enzymes producing intracellular second messengers, which may account for the functional and structural ovarian phenotypes characteristic of PCOS (e.g., thecal cell hypertrophy, hyperandrogenemia, follicular growth arrest, and anovulation) as well as alterations in cellular metabolism (e.g., obesity) frequently associated with PCOS [20].