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Protein

Gonadotropin-releasing hormone receptor

Gene

GNRHR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-375281 Hormone ligand-binding receptors
R-HSA-416476 G alpha (q) signalling events

Protein family/group databases

TCDBi9.A.14.10.1 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
Gonadotropin-releasing hormone receptor
Short name:
GnRH receptor
Short name:
GnRH-R
Gene namesi
Name:GNRHR
Synonyms:GRHR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109163.6
HGNCiHGNC:4421 GNRHR
MIMi138850 gene
neXtProtiNX_P30968

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 38ExtracellularSequence analysisAdd BLAST38
Transmembranei39 – 58Helical; Name=1Sequence analysisAdd BLAST20
Topological domaini59 – 77CytoplasmicSequence analysisAdd BLAST19
Transmembranei78 – 97Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini98 – 115ExtracellularSequence analysisAdd BLAST18
Transmembranei116 – 137Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini138 – 164CytoplasmicSequence analysisAdd BLAST27
Transmembranei165 – 184Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini185 – 212ExtracellularSequence analysisAdd BLAST28
Transmembranei213 – 232Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini233 – 281CytoplasmicSequence analysisAdd BLAST49
Transmembranei282 – 300Helical; Name=6Sequence analysisAdd BLAST19
Topological domaini301 – 306ExtracellularSequence analysis6
Transmembranei307 – 326Helical; Name=7Sequence analysisAdd BLAST20
Topological domaini327 – 328CytoplasmicSequence analysis2

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 7 with or without anosmia (HH7)12 Publications
The disease is caused by mutations 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 GNRHR as well as in other HH-associated genes including FGFR1 (PubMed:23643382).1 Publication
Disease descriptionA 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).
See also OMIM:146110
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01931110N → K in HH7; is able to bind GnRH but with a reduced affinity in vitro. 1 PublicationCorresponds to variant dbSNP:rs104893843EnsemblClinVar.1
Natural variantiVAR_07297018N → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs774317793Ensembl.1
Natural variantiVAR_07297137I → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs886907903Ensembl.1
Natural variantiVAR_06996083L → V in HH7; the patient also carries a mutation in FGFR1. 1 Publication1
Natural variantiVAR_07297290E → D in HH7. 1 Publication1
Natural variantiVAR_01931290E → K in HH7; virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover; impairs GnRHR-effector coupling. 2 PublicationsCorresponds to variant dbSNP:rs104893844EnsemblClinVar.1
Natural variantiVAR_019313106Q → R in HH7; some patients also carry mutations in FGFR1; decreases but does not eliminate GnRH binding. 6 PublicationsCorresponds to variant dbSNP:rs104893836EnsemblClinVar.1
Natural variantiVAR_019314129A → D in HH7; complete loss of function. 2 PublicationsCorresponds to variant dbSNP:rs104893838EnsemblClinVar.1
Natural variantiVAR_019315139R → H in HH7; completely eliminates detectable GnRH-binding activity and prevents GnRH-induced stimulation of inositol phosphate accumulation in vitro. 2 PublicationsCorresponds to variant dbSNP:rs104893842EnsemblClinVar.1
Natural variantiVAR_072973146P → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs144900788EnsemblClinVar.1
Natural variantiVAR_019316168S → R in HH7; complete loss of the receptor-mediated signaling response. 1 PublicationCorresponds to variant dbSNP:rs104893840EnsemblClinVar.1
Natural variantiVAR_019317171A → T in HH7; complete loss of ligand binding and receptor activation; specific receptor binding of radioisotope-labeled GnRH ligand is undetectable in transfected cells. 1 PublicationCorresponds to variant dbSNP:rs74452732EnsemblClinVar.1
Natural variantiVAR_019318217S → R in HH7; altered hormone binding. 1 PublicationCorresponds to variant dbSNP:rs104893839EnsemblClinVar.1
Natural variantiVAR_019319262R → Q in HH7; unknown pathological significance; some patients also carry mutations in FGFR1; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C. 6 PublicationsCorresponds to variant dbSNP:rs104893837EnsemblClinVar.1
Natural variantiVAR_072974266L → R in HH7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs148499544Ensembl.1
Natural variantiVAR_019320284Y → C in HH7; minimal effects upon receptor affinity but receptor expression decreased. 1 PublicationCorresponds to variant dbSNP:rs28933074EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism

Organism-specific databases

DisGeNETi2798
GeneReviewsiGNRHR
MalaCardsiGNRHR
MIMi146110 phenotype
OpenTargetsiENSG00000109163
Orphaneti432 Normosmic congenital hypogonadotropic hypogonadism
PharmGKBiPA28800

Chemistry databases

ChEMBLiCHEMBL1855
DrugBankiDB00106 Abarelix
DB06719 Buserelin
DB00050 Cetrorelix
DB01406 Danazol
DB06699 Degarelix
DB06785 Ganirelix
DB00644 Gonadorelin
DB00014 Goserelin
DB06788 Histrelin
DB00007 Leuprolide
DB00666 Nafarelin
DB05694 NBI-56418
DB06825 Triptorelin
GuidetoPHARMACOLOGYi256

Polymorphism and mutation databases

BioMutaiGNRHR
DMDMi399777

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694871 – 328Gonadotropin-releasing hormone receptorAdd BLAST328

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi18N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi102N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi114 ↔ 196PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP30968
PaxDbiP30968
PeptideAtlasiP30968
PRIDEiP30968

PTM databases

PhosphoSitePlusiP30968

Expressioni

Tissue specificityi

Pituitary, ovary, testis, breast and prostate but not in liver and spleen.

Gene expression databases

BgeeiENSG00000109163
CleanExiHS_GNRHR
GenevisibleiP30968 HS

Organism-specific databases

HPAiHPA013424

Interactioni

Protein-protein interaction databases

BioGridi109060, 3 interactors
STRINGi9606.ENSP00000226413

Chemistry databases

BindingDBiP30968

Structurei

3D structure databases

ProteinModelPortaliP30968
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00760000119156
HOGENOMiHOG000251590
HOVERGENiHBG009082
InParanoidiP30968
KOiK04280
OMAiKGYFQCV
OrthoDBiEOG091G0ZDG
PhylomeDBiP30968
TreeFamiTF106499

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR001658 GphnRH_fam_rcpt
IPR027982 GphnRH_rcpt
PANTHERiPTHR24241:SF22 PTHR24241:SF22, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00529 GNADOTRPHINR
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30968-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MANSASPEQN QNHCSAINNS IPLMQGNLPT LTLSGKIRVT VTFFLFLLSA
60 70 80 90 100
TFNASFLLKL QKWTQKKEKG KKLSRMKLLL KHLTLANLLE TLIVMPLDGM
110 120 130 140 150
WNITVQWYAG ELLCKVLSYL KLFSMYAPAF MMVVISLDRS LAITRPLALK
160 170 180 190 200
SNSKVGQSMV GLAWILSSVF AGPQLYIFRM IHLADSSGQT KVFSQCVTHC
210 220 230 240 250
SFSQWWHQAF YNFFTFSCLF IIPLFIMLIC NAKIIFTLTR VLHQDPHELQ
260 270 280 290 300
LNQSKNNIPR ARLKTLKMTV AFATSFTVCW TPYYVLGIWY WFDPEMLNRL
310 320
SDPVNHFFFL FAFLNPCFDP LIYGYFSL
Length:328
Mass (Da):37,731
Last modified:July 1, 1993 - v1
Checksum:iD02B2EA2F4246D7B
GO
Isoform 2 (identifier: P30968-2) [UniParc]FASTAAdd to basket
Also known as: Truncated

The sequence of this isoform differs from the canonical sequence as follows:
     176-328: YIFRMIHLAD...DPLIYGYFSL → PLHHPSFHHA...LLCPRNLVLV

Show »
Length:249
Mass (Da):27,727
Checksum:i5801B1C5E5FBA64A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti247H → T in CAB17082 (PubMed:10366411).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01931110N → K in HH7; is able to bind GnRH but with a reduced affinity in vitro. 1 PublicationCorresponds to variant dbSNP:rs104893843EnsemblClinVar.1
Natural variantiVAR_07297018N → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs774317793Ensembl.1
Natural variantiVAR_07297137I → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs886907903Ensembl.1
Natural variantiVAR_06996083L → V in HH7; the patient also carries a mutation in FGFR1. 1 Publication1
Natural variantiVAR_07297290E → D in HH7. 1 Publication1
Natural variantiVAR_01931290E → K in HH7; virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover; impairs GnRHR-effector coupling. 2 PublicationsCorresponds to variant dbSNP:rs104893844EnsemblClinVar.1
Natural variantiVAR_019313106Q → R in HH7; some patients also carry mutations in FGFR1; decreases but does not eliminate GnRH binding. 6 PublicationsCorresponds to variant dbSNP:rs104893836EnsemblClinVar.1
Natural variantiVAR_019314129A → D in HH7; complete loss of function. 2 PublicationsCorresponds to variant dbSNP:rs104893838EnsemblClinVar.1
Natural variantiVAR_019315139R → H in HH7; completely eliminates detectable GnRH-binding activity and prevents GnRH-induced stimulation of inositol phosphate accumulation in vitro. 2 PublicationsCorresponds to variant dbSNP:rs104893842EnsemblClinVar.1
Natural variantiVAR_072973146P → S in HH7. 1 PublicationCorresponds to variant dbSNP:rs144900788EnsemblClinVar.1
Natural variantiVAR_019316168S → R in HH7; complete loss of the receptor-mediated signaling response. 1 PublicationCorresponds to variant dbSNP:rs104893840EnsemblClinVar.1
Natural variantiVAR_019317171A → T in HH7; complete loss of ligand binding and receptor activation; specific receptor binding of radioisotope-labeled GnRH ligand is undetectable in transfected cells. 1 PublicationCorresponds to variant dbSNP:rs74452732EnsemblClinVar.1
Natural variantiVAR_019318217S → R in HH7; altered hormone binding. 1 PublicationCorresponds to variant dbSNP:rs104893839EnsemblClinVar.1
Natural variantiVAR_019319262R → Q in HH7; unknown pathological significance; some patients also carry mutations in FGFR1; minimal effects upon receptor affinity but expression decreased; altered activation of phospholipase C. 6 PublicationsCorresponds to variant dbSNP:rs104893837EnsemblClinVar.1
Natural variantiVAR_072974266L → R in HH7; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs148499544Ensembl.1
Natural variantiVAR_019320284Y → C in HH7; minimal effects upon receptor affinity but receptor expression decreased. 1 PublicationCorresponds to variant dbSNP:rs28933074EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001914176 – 328YIFRM…GYFSL → PLHHPSFHHADLQCKNHLHP DTGPSSGPPRTTTESVQEQY TKSTAEDSKNDGCICHFIYC LLDSLLCPRNLVLV in isoform 2. 1 PublicationAdd BLAST153

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L03380 mRNA Translation: AAA35918.1
L07949 mRNA Translation: AAA35917.1
S60587 mRNA Translation: AAB26287.1
S77472 mRNA Translation: AAB33884.1
AF001952, AF001950, AF001951 Genomic DNA Translation: AAB71348.1
Z81148 mRNA Translation: CAB03541.1
AY392011 mRNA Translation: AAR92228.1
BC113546 mRNA Translation: AAI13547.1
Z99995 Genomic DNA Translation: CAB17082.1
CCDSiCCDS3517.1 [P30968-1]
CCDS47064.1 [P30968-2]
PIRiJC1353
RefSeqiNP_000397.1, NM_000406.2 [P30968-1]
NP_001012781.1, NM_001012763.1 [P30968-2]
UniGeneiHs.407587

Genome annotation databases

EnsembliENST00000226413; ENSP00000226413; ENSG00000109163 [P30968-1]
ENST00000420975; ENSP00000397561; ENSG00000109163 [P30968-2]
GeneIDi2798
KEGGihsa:2798
UCSCiuc003hdm.4 human [P30968-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGNRHR_HUMAN
AccessioniPrimary (citable) accession number: P30968
Secondary accession number(s): O75793, Q14D13, Q92644
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: March 28, 2018
This is version 174 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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