GNRHR
Chr 4ARgonadotropin releasing hormone receptor
Also known as: GNRHR1, GRHR, HH7, LHRHR, LRHR
This gene encodes the gonadotropin-releasing hormone receptor, a G-protein coupled receptor that mediates GnRH signaling to stimulate release of luteinizing hormone and follicle-stimulating hormone from pituitary gonadotropes. Mutations cause autosomal recessive hypogonadotropic hypogonadism without anosmia, affecting reproductive hormone regulation and sexual development. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.75), and detailed clinical management guidance is available in GeneReviews.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GNRHR · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools