Abstract
Makorin RING finger protein 3 (MKRN3) is a key inhibitor of the hypothalamic-pituitary-gonadal axis. Loss-of-function mutations in MKRN3 cause familial and sporadic central precocious puberty (CPP), while polymorphisms are associated with age at menarche. To date, 115 patients with CPP carrying MKRN3 mutations have been described, harboring 48 different genetic variants. The prevalence of MKRN3 mutations in genetically screened populations with CPP is estimated at 9.0%. Girls are more commonly and more seriously affected than boys. MKRN3 is expressed in humans and rodents in the central nervous system. Circulating levels in humans and hypothalamic expression in rodents decrease during pubertal progression. Although some MKRN3 regulators have been identified, the precise mechanism by which MKRN3 inhibits the hypothalamic-pituitary-gonadal axis remains elusive. The role of makorins in developmental physiology and organ differentiation and the role of maternal imprinting are discussed herein.