The p. M265 V (c.793A > G) and p.L597I (c.1789C > A) variants exclusively existed in Chinese POF patients, former located in extracellular domain (ECD) and later in TMD, wherein the p.L597I can suppress FSH-induced cAMP production and ERK1/2 phosphorylation, thereby stimulating the POF phenotype (151). This evidence concerns the gene BRD2 and premature menopause.