GNRHR

Protein identityUniProt · HPA

UniProt accession

P30968

Gene

GNRHR

Ensembl

ENSG00000109163

Chromosome

4

Canonical length

328 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins, Transporters

OverviewNCBI Gene

This gene encodes the receptor for type 1 gonadotropin-releasing hormone. This receptor is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate. Following binding of gonadotropin-releasing hormone, the receptor associates with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Activation of the receptor ultimately causes the release of gonadotropic luteinizing hormone (LH) and follicle stimulating hormone (FSH). Defects in this gene are a cause of hypogonadotropic hypogonadism (HH). Alternative splicing results in multiple transcript variants encoding different isoforms. More than 18 transcription initiation sites in the 5' region and multiple polyA signals in the 3' region have been identified for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

328 residues, UniProt reviewed canonical sequence.

>P30968|GNRHR
     1  MANSASPEQN QNHCSAINNS IPLMQGNLPT LTLSGKIRVT VTFFLFLLSA TFNASFLLKL
    61  QKWTQKKEKG KKLSRMKLLL KHLTLANLLE TLIVMPLDGM WNITVQWYAG ELLCKVLSYL
   121  KLFSMYAPAF MMVVISLDRS LAITRPLALK SNSKVGQSMV GLAWILSSVF AGPQLYIFRM
   181  IHLADSSGQT KVFSQCVTHC SFSQWWHQAF YNFFTFSCLF IIPLFIMLIC NAKIIFTLTR
   241  VLHQDPHELQ LNQSKNNIPR ARLKTLKMTV AFATSFTVCW TPYYVLGIWY WFDPEMLNRL
   301  SDPVNHFFFL FAFLNPCFDP LIYGYFSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GNRHR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

12 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GNRHR.

Disease | AllUniProt

Conditions GNRHR is implicated in, by any mechanism.

• Hypogonadotropic hypogonadism 7 with or without anosmia (HH7) MIM:146110

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 219 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypogonadotropic hypogonadism 7 with or without anosmia
• Hypogonadotropic hypogonadism
• GNRHR-related disorder
• Isolated congenital hypogonadotropic hypogonadism
• See cases

Disease | ImmuneIEDB

Conditions an epitope on GNRHR was assayed in.

• ovarian disease B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against GNRHR are reported. Each links to that disease's full target list.

Showing 0 of 1 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for GNRHR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.75

gnomAD pLI

0.07

gnomAD missense Z

0.3

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to hormone stimulus
• G protein-coupled receptor signaling pathway
• gonadotropin secretion

Molecular functions

• gonadotropin-releasing hormone receptor activity

Cellular components

• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Gonadotrophin-releasing hormone receptor family
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Hypogonadotropic hypogonadism
• Membrane
• Receptor
• Transducer
• Transmembrane
• Transmembrane helix