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GNRH1

Function

Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.

Involvement in disease

Hypogonadotropic hypogonadism 12 with or without anosmia

HH12

A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).

None

The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in GNRH1 as well as in other HH-associated genes including PROKR2 and FGFR1 (PubMed:23643382).

Post-translational modifications

Gonadoliberin-1

The precursor is cleaved by ACE, which removes the Gly-Lys-Arg peptide at the C-terminus, leading to mature hormone (PubMed:10336644, PubMed:7683654). The mature form of Gonadoliberin-1 is also cleaved and degraded by ACE (PubMed:2983326, PubMed:7683654).

Sequence Similarities

Belongs to the GnRH family.

Cellular localization

Alternative names

GNRH, GRH, LHRH, GNRH1, Progonadoliberin-1, Progonadoliberin I

swissprot:P01148 omim:152760 entrezGene:2796