Human genetics of GPR54

Idiopathic hypogonadotropic hypogonadism (IHH) is a condition characterized by absence of sexual maturation in the setting of low sex steroids and low/normal gonadotropins. Despite its rarity, considerable genetic heterogeneity and phenotypic variability exists in this disorder. Loss of function mutations in a G protein coupled receptor, GPR54, have been shown to cause IHH. Although mutations in GPR54 are not a common cause of this condition, patients bearing mutations are critical to explore genotype-phenotype correlations and gene function. In this review, we will examine the human genetics studies of GPR54, the phenotypic implications of mutations in this gene, and the emerging roles of the kisspeptin/GPR54 pathway.