GNRHR (Gonadotropin Releasing Hormone Receptor)
Key regulator of the hypothalamic-pituitary-gonadal axis; mutations cause hypogonadotropic hypogonadism.
Gene Information Card
| Symbol | GNRHR |
|---|---|
| Full Name | Gonadotropin Releasing Hormone Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 4q13.2 |
| NCBI Gene ID | 2798 ncbi.nlm.nih.gov/gene/2798 |
| Ensembl ID | ENSG00000109163 |
| UniProt ID | P30968 |
| OMIM ID | 138850 |
| HGNC ID | 4421 |
| Aliases | GRHR, GNRHR1, LHRHR, GnRH-R |
Description
The GNRHR gene encodes the gonadotropin-releasing hormone receptor, a G-protein coupled receptor expressed on pituitary gonadotropes. Binding of GnRH stimulates release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), essential for reproductive function. Loss-of-function mutations cause idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome) or normosmic IHH.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypogonadotropic Hypogonadism | Loss-of-function mutations impair GnRH signaling, reducing LH/FSH secretion. | ClinVar, OMIM |
| Kallmann Syndrome | Defective GnRH receptor prevents gonadotropin release, often with anosmia. | OMIM #147950 |
| Delayed Puberty | Heterozygous variants may contribute to constitutional delay of growth and puberty. | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pituitary | 12.5 | High |
| Brain (cerebellum) | 1.2 | Low |
| Testis | 0.8 | Low |
| Ovary | 0.5 | Low |
| Placenta | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LβT2 (mouse gonadotrope) | 15.0 | Model cell line for GnRH signaling |
| HEK293 | 0.1 | Low endogenous expression |
| HeLa | 0.0 | No detectable expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.317A>G (p.Gln106Arg) | Missense | Common in IHH | Loss of function; reduced ligand binding |
| c.785G>A (p.Arg262Gln) | Missense | Rare | Impaired receptor trafficking |
| c.18C>A (p.Tyr6*) | Nonsense | Very rare | Premature truncation; complete loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations; cause hypogonadotropic hypogonadism via impaired receptor activation or cell surface expression.
Gain of Function (GOF)
Not described in literature.
Dominant Negative (DN)
Not reported; disease is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • gonadotropin-releasing hormone receptor activity |
| • plasma membrane | • signal transduction |
| • response to hormone |
Pathways
• GnRH signaling pathway (KEGG: hsa04912)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
Protein Summary
The GnRH receptor is a 328-amino acid G-protein coupled receptor with seven transmembrane domains. It binds GnRH with high affinity, activating phospholipase C via Gq/11, leading to calcium mobilization and MAPK activation. The receptor lacks a cytoplasmic C-terminal tail, resulting in slow desensitization. Post-translational modifications include N-glycosylation at Asn18 and Asn102.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNRHR Knockout HEK293 Cell Line | EDJ-KQ3968 | Human | 2798 | Details Get a Quote |
| GNRHR Knockout HeLa Cell Line | EDJ-KQ53375 | Human | 2798 | Details Get a Quote |
| GNRHR Knockout A-549 Cell Line | EDJ-KQ61851 | Human | 2798 | Details Get a Quote |
| GNRHR Knockout HCT 116 Cell Line | EDJ-KQ70336 | Human | 2798 | Details Get a Quote |
