GNRHR_HUMAN
ID GNRHR_HUMAN Reviewed; 328 AA.
AC P30968; O75793; Q14D13; Q92644;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Gonadotropin-releasing hormone receptor;
DE Short=GnRH receptor;
DE Short=GnRH-R;
GN Name=GNRHR; Synonyms=GRHR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=1333190; DOI=10.1016/0006-291x(92)91556-6;
RA Kakar S.S., Musgrove L.C., Devor D.C., Sellers J.C., Neill J.D.;
RT "Cloning, sequencing, and expression of human gonadotropin releasing
RT hormone (GnRH) receptor.";
RL Biochem. Biophys. Res. Commun. 189:289-295(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=8386108; DOI=10.1016/0303-7207(93)90278-r;
RA Chi L., Zhou W., Prikhozhan A., Flanagan C.A., Davidson J.S., Golembo M.,
RA Illing N., Millar R.P., Sealfon S.C.;
RT "Cloning and characterization of the human GnRH receptor.";
RL Mol. Cell. Endocrinol. 91:R1-R6(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7534732; DOI=10.1016/0303-7207(94)90196-1;
RA Kakar S.S., Grizzle W.E., Neill J.D.;
RT "The nucleotide sequences of human GnRH receptors in breast and ovarian
RT tumors are identical with that found in pituitary.";
RL Mol. Cell. Endocrinol. 106:145-149(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=9272108; DOI=10.1530/eje.0.1370183;
RA Kakar S.S.;
RT "Molecular structure of the human gonadotropin-releasing hormone receptor
RT gene.";
RL Eur. J. Endocrinol. 137:183-192(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Pituitary;
RX PubMed=9259321; DOI=10.1210/mend.11.9.9966;
RA Grosse R., Schoneberg T., Schultz G., Gudermann T.;
RT "Inhibition of gonadotropin-releasing hormone receptor signaling by
RT expression of a splice variant of the human receptor.";
RL Mol. Endocrinol. 11:1305-1318(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 247-328 (ISOFORM 1).
RX PubMed=10366411; DOI=10.1530/eje.0.1400561;
RA Kottler M.L., Bergametti F., Carre M.C., Morice S., Decoret E.,
RA Lagarde J.P., Starzec A., Counis R.;
RT "Tissue-specific pattern of variant transcripts of the human gonadotropin-
RT releasing hormone receptor gene.";
RL Eur. J. Endocrinol. 140:561-569(1999).
RN [9]
RP VARIANTS HH7 ARG-106 AND GLN-262, AND CHARACTERIZATION OF VARIANTS HH7
RP ARG-106 AND GLN-262.
RX PubMed=9371856; DOI=10.1056/nejm199711273372205;
RA de Roux N., Young J., Misrahi M., Genet R., Chanson P., Schaison G.,
RA Milgrom E.;
RT "A family with hypogonadotropic hypogonadism and mutations in the
RT gonadotropin-releasing hormone receptor.";
RL N. Engl. J. Med. 337:1597-1602(1997).
RN [10]
RP VARIANTS HH7 GLN-262 AND CYS-284, AND CHARACTERIZATION OF VARIANTS HH7
RP GLN-262 AND CYS-284.
RX PubMed=9425890; DOI=10.1038/ng0198-14;
RA Layman L.C., Cohen D.P., Jin M., Xie J., Li Z., Reindollar R.H.,
RA Bolbolan S., Bick D.P., Sherins R.R., Duck L.W., Musgrove L.C.,
RA Sellers J.C., Neill J.D.;
RT "Mutations in gonadotropin-releasing hormone receptor gene cause
RT hypogonadotropic hypogonadism.";
RL Nat. Genet. 18:14-15(1998).
RN [11]
RP VARIANTS HH7 ARG-106; ARG-217 AND GLN-262, AND CHARACTERIZATION OF VARIANTS
RP HH7 ARG-106; ARG-217 AND GLN-262.
RX PubMed=10022417; DOI=10.1210/jcem.84.2.5449;
RA de Roux N., Young J., Brailly-Tabard S., Misrahi M., Milgrom E.,
RA Schaison G.;
RT "The same molecular defects of the gonadotropin-releasing hormone receptor
RT determine a variable degree of hypogonadism in affected kindred.";
RL J. Clin. Endocrinol. Metab. 84:567-572(1999).
RN [12]
RP VARIANTS HH7 ASP-129 AND GLN-262, AND CHARACTERIZATION OF VARIANT HH7
RP ASP-129.
RX PubMed=10084584; DOI=10.1210/jcem.84.3.5518;
RA Caron P., Chauvin S., Christin-Maitre S., Bennet A., Lahlou N., Counis R.,
RA Bouchard P., Kottler M.-L.;
RT "Resistance of hypogonadic patients with mutated GnRH receptor genes to
RT pulsatile GnRH administration.";
RL J. Clin. Endocrinol. Metab. 84:990-996(1999).
RN [13]
RP VARIANT HH7 ARG-168, AND CHARACTERIZATION OF VARIANT HH7 ARG-168.
RX PubMed=10523035; DOI=10.1210/jcem.84.10.6042;
RA Pralong F.P., Gomez F., Castillo E., Cotecchia S., Abuin L., Aubert M.L.,
RA Portmann L., Gaillard R.C.;
RT "Complete hypogonadotropic hypogonadism associated with a novel
RT inactivating mutation of the gonadotropin-releasing hormone receptor.";
RL J. Clin. Endocrinol. Metab. 84:3811-3816(1999).
RN [14]
RP VARIANT HH7 ARG-106.
RX PubMed=11397842; DOI=10.1210/jcem.86.6.7542;
RA Pitteloud N., Boepple P.A., DeCruz S., Valkenburgh S.B., Crowley W.F. Jr.,
RA Hayes F.J.;
RT "The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism:
RT spontaneous reversal associated with a homozygous mutation in the
RT gonadotropin-releasing hormone receptor.";
RL J. Clin. Endocrinol. Metab. 86:2470-2475(2001).
RN [15]
RP VARIANT HH7 LYS-90.
RX PubMed=11318785; DOI=10.1046/j.1365-2265.2001.01211.x;
RA Soederlund D., Canto P., de la Chesnaye E., Ulloa-Aguirre A., Mendez J.P.;
RT "A novel homozygous mutation in the second transmembrane domain of the
RT gonadotrophin releasing hormone receptor gene.";
RL Clin. Endocrinol. (Oxf.) 54:493-498(2001).
RN [16]
RP VARIANTS HH7 LYS-10; ARG-106 AND HIS-139, AND CHARACTERIZATION OF VARIANTS
RP HH7 LYS-10; ARG-106 AND HIS-139.
RX PubMed=11397871; DOI=10.1210/jcem.86.6.7551;
RA Costa E.M.F., Bedecarrats G.Y., Mendonca B.B., Arnhold I.J.P., Kaiser U.B.,
RA Latronico A.C.;
RT "Two novel mutations in the gonadotropin-releasing hormone receptor gene in
RT Brazilian patients with hypogonadotropic hypogonadism and normal
RT olfaction.";
RL J. Clin. Endocrinol. Metab. 86:2680-2686(2001).
RN [17]
RP CHARACTERIZATION OF VARIANT HH7 LYS-90.
RX PubMed=11994356; DOI=10.1210/jcem.87.5.8386;
RA Maya-Nunez G., Janovick J.A., Ulloa-Aguirre A., Soederlund D., Conn P.M.,
RA Mendez J.P.;
RT "Molecular basis of hypogonadotropic hypogonadism: restoration of mutant
RT (E(90)K) GnRH receptor function by a deletion at a distant site.";
RL J. Clin. Endocrinol. Metab. 87:2144-2149(2002).
RN [18]
RP VARIANT HH7 THR-171, AND CHARACTERIZATION OF VARIANT HH7 THR-171.
RX PubMed=12679486; DOI=10.1210/jc.2002-020005;
RA Karges B., Karges W., Mine M., Ludwig L., Kuehne R., Milgrom E.,
RA de Roux N.;
RT "Mutation Ala(171)Thr stabilizes the gonadotropin-releasing hormone
RT receptor in its inactive conformation, causing familial hypogonadotropic
RT hypogonadism.";
RL J. Clin. Endocrinol. Metab. 88:1873-1879(2003).
RN [19]
RP VARIANTS HH7 VAL-83; ARG-106 AND GLN-262.
RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008;
RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B.,
RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M.,
RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A.,
RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G.,
RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K.,
RA Pitteloud N.;
RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in
RT individuals with congenital hypogonadotropic hypogonadism.";
RL Am. J. Hum. Genet. 92:725-743(2013).
RN [20]
RP VARIANTS HH7 SER-18; SER-37; ASP-90; ARG-106; ASP-129; HIS-139; SER-146;
RP GLN-262 AND ARG-266.
RX PubMed=25077900; DOI=10.1210/jc.2014-2110;
RA Marcos S., Sarfati J., Leroy C., Fouveaut C., Parent P., Metz C.,
RA Wolczynski S., Gerard M., Bieth E., Kurtz F., Verier-Mine O., Perrin L.,
RA Archambeaud F., Cabrol S., Rodien P., Hove H., Prescott T., Lacombe D.,
RA Christin-Maitre S., Touraine P., Hieronimus S., Dewailly D., Young J.,
RA Pugeat M., Hardelin J.P., Dode C.;
RT "The prevalence of CHD7 missense versus truncating mutations is higher in
RT patients with Kallmann syndrome than in typical CHARGE patients.";
RL J. Clin. Endocrinol. Metab. 99:E2138-2143(2014).
CC -!- FUNCTION: Receptor for gonadotropin releasing hormone (GnRH) that
CC mediates the action of GnRH to stimulate the secretion of the
CC gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating
CC hormone (FSH). This receptor mediates its action by association with G-
CC proteins that activate a phosphatidylinositol-calcium second messenger
CC system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30968-1; Sequence=Displayed;
CC Name=2; Synonyms=Truncated;
CC IsoId=P30968-2; Sequence=VSP_001914;
CC -!- TISSUE SPECIFICITY: Pituitary, ovary, testis, breast and prostate but
CC not in liver and spleen.
CC -!- DISEASE: Hypogonadotropic hypogonadism 7 with or without anosmia (HH7)
CC [MIM:146110]: A disorder characterized by absent or incomplete sexual
CC maturation by the age of 18 years, in conjunction with low levels of
CC circulating gonadotropins and testosterone and no other abnormalities
CC of the hypothalamic-pituitary axis. In some cases, it is associated
CC with non-reproductive phenotypes, such as anosmia, cleft palate, and
CC sensorineural hearing loss. Anosmia or hyposmia is related to the
CC absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism
CC is due to deficiency in gonadotropin-releasing hormone and probably
CC results from a failure of embryonic migration of gonadotropin-releasing
CC hormone-synthesizing neurons. In the presence of anosmia, idiopathic
CC hypogonadotropic hypogonadism is referred to as Kallmann syndrome,
CC whereas in the presence of a normal sense of smell, it has been termed
CC normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
CC {ECO:0000269|PubMed:10022417, ECO:0000269|PubMed:10084584,
CC ECO:0000269|PubMed:10523035, ECO:0000269|PubMed:11318785,
CC ECO:0000269|PubMed:11397842, ECO:0000269|PubMed:11397871,
CC ECO:0000269|PubMed:11994356, ECO:0000269|PubMed:12679486,
CC ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900,
CC ECO:0000269|PubMed:9371856, ECO:0000269|PubMed:9425890}. Note=The
CC disease is caused by variants affecting distinct genetic loci,
CC including the gene represented in this entry. The genetics of
CC hypogonadotropic hypogonadism involves various modes of transmission.
CC Oligogenic inheritance has been reported in some patients carrying
CC mutations in GNRHR as well as in other HH-associated genes including
CC FGFR1 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; L03380; AAA35918.1; -; mRNA.
DR EMBL; L07949; AAA35917.1; -; mRNA.
DR EMBL; S60587; AAB26287.1; -; mRNA.
DR EMBL; S77472; AAB33884.1; -; mRNA.
DR EMBL; AF001952; AAB71348.1; -; Genomic_DNA.
DR EMBL; AF001950; AAB71348.1; JOINED; Genomic_DNA.
DR EMBL; AF001951; AAB71348.1; JOINED; Genomic_DNA.
DR EMBL; Z81148; CAB03541.1; -; mRNA.
DR EMBL; AY392011; AAR92228.1; -; mRNA.
DR EMBL; BC113546; AAI13547.1; -; mRNA.
DR EMBL; Z99995; CAB17082.1; -; Genomic_DNA.
DR CCDS; CCDS3517.1; -. [P30968-1]
DR CCDS; CCDS47064.1; -. [P30968-2]
DR PIR; JC1353; JC1353.
DR RefSeq; NP_000397.1; NM_000406.2. [P30968-1]
DR RefSeq; NP_001012781.1; NM_001012763.1. [P30968-2]
DR PDB; 7BR3; X-ray; 2.79 A; A=1-242, A=257-328.
DR PDBsum; 7BR3; -.
DR AlphaFoldDB; P30968; -.
DR SMR; P30968; -.
DR BioGRID; 109060; 6.
DR IntAct; P30968; 4.
DR MINT; P30968; -.
DR STRING; 9606.ENSP00000226413; -.
DR BindingDB; P30968; -.
DR ChEMBL; CHEMBL1855; -.
DR DrugBank; DB00106; Abarelix.
DR DrugBank; DB06719; Buserelin.
DR DrugBank; DB00050; Cetrorelix.
DR DrugBank; DB01406; Danazol.
DR DrugBank; DB06699; Degarelix.
DR DrugBank; DB11979; Elagolix.
DR DrugBank; DB06785; Ganirelix.
DR DrugBank; DB11619; Gestrinone.
DR DrugBank; DB00644; Gonadorelin.
DR DrugBank; DB00014; Goserelin.
DR DrugBank; DB06788; Histrelin.
DR DrugBank; DB00007; Leuprolide.
DR DrugBank; DB00666; Nafarelin.
DR DrugBank; DB11853; Relugolix.
DR DrugBank; DB06494; Sufugolix.
DR DrugBank; DB05624; Teverelix.
DR DrugBank; DB06825; Triptorelin.
DR DrugCentral; P30968; -.
DR GuidetoPHARMACOLOGY; 256; -.
DR TCDB; 9.A.14.10.1; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P30968; 2 sites.
DR PhosphoSitePlus; P30968; -.
DR BioMuta; GNRHR; -.
DR DMDM; 399777; -.
DR EPD; P30968; -.
DR PaxDb; P30968; -.
DR PeptideAtlas; P30968; -.
DR PRIDE; P30968; -.
DR ABCD; P30968; 2 sequenced antibodies.
DR Antibodypedia; 12675; 441 antibodies from 37 providers.
DR DNASU; 2798; -.
DR Ensembl; ENST00000226413.5; ENSP00000226413.5; ENSG00000109163.7. [P30968-1]
DR Ensembl; ENST00000420975.2; ENSP00000397561.2; ENSG00000109163.7. [P30968-2]
DR GeneID; 2798; -.
DR KEGG; hsa:2798; -.
DR MANE-Select; ENST00000226413.5; ENSP00000226413.5; NM_000406.3; NP_000397.1.
DR UCSC; uc003hdm.4; human. [P30968-1]
DR CTD; 2798; -.
DR DisGeNET; 2798; -.
DR GeneCards; GNRHR; -.
DR GeneReviews; GNRHR; -.
DR HGNC; HGNC:4421; GNRHR.
DR HPA; ENSG00000109163; Group enriched (brain, pituitary gland).
DR MalaCards; GNRHR; -.
DR MIM; 138850; gene.
DR MIM; 146110; phenotype.
DR neXtProt; NX_P30968; -.
DR OpenTargets; ENSG00000109163; -.
DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism.
DR PharmGKB; PA28800; -.
DR VEuPathDB; HostDB:ENSG00000109163; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244841; -.
DR HOGENOM; CLU_009579_15_2_1; -.
DR InParanoid; P30968; -.
DR OMA; SEPVNHF; -.
DR OrthoDB; 858238at2759; -.
DR PhylomeDB; P30968; -.
DR TreeFam; TF106499; -.
DR PathwayCommons; P30968; -.
DR Reactome; R-HSA-375281; Hormone ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P30968; -.
DR SIGNOR; P30968; -.
DR BioGRID-ORCS; 2798; 9 hits in 1065 CRISPR screens.
DR GeneWiki; GNRHR; -.
DR GenomeRNAi; 2798; -.
DR Pharos; P30968; Tclin.
DR PRO; PR:P30968; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P30968; protein.
DR Bgee; ENSG00000109163; Expressed in adrenal tissue and 81 other tissues.
DR Genevisible; P30968; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0004968; F:gonadotropin-releasing hormone receptor activity; IDA:ProtInc.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0032274; P:gonadotropin secretion; NAS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001658; GphnRH_fam_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00529; GNADOTRPHINR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Hypogonadotropic hypogonadism; Membrane; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..328
FT /note="Gonadotropin-releasing hormone receptor"
FT /id="PRO_0000069487"
FT TOPO_DOM 1..38
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..58
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 59..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..97
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 98..115
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..184
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..212
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..232
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..300
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 301..306
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 307..326
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..328
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 114..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 176..328
FT /note="YIFRMIHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFTFSCLFIIPLFIM
FT LICNAKIIFTLTRVLHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTPYYVL
FT GIWYWFDPEMLNRLSDPVNHFFFLFAFLNPCFDPLIYGYFSL -> PLHHPSFHHADLQ
FT CKNHLHPDTGPSSGPPRTTTESVQEQYTKSTAEDSKNDGCICHFIYCLLDSLLCPRNLV
FT LV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9259321"
FT /id="VSP_001914"
FT VARIANT 10
FT /note="N -> K (in HH7; is able to bind GnRH but with a
FT reduced affinity in vitro; dbSNP:rs104893843)"
FT /evidence="ECO:0000269|PubMed:11397871"
FT /id="VAR_019311"
FT VARIANT 18
FT /note="N -> S (in HH7; dbSNP:rs774317793)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072970"
FT VARIANT 37
FT /note="I -> S (in HH7; dbSNP:rs886907903)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072971"
FT VARIANT 83
FT /note="L -> V (in HH7; the patient also carries a mutation
FT in FGFR1; dbSNP:rs1391808526)"
FT /evidence="ECO:0000269|PubMed:23643382"
FT /id="VAR_069960"
FT VARIANT 90
FT /note="E -> D (in HH7)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072972"
FT VARIANT 90
FT /note="E -> K (in HH7; virtual abolition of GnRH agonist
FT binding and agonist-stimulated phosphoinositide turnover;
FT impairs GnRHR-effector coupling; dbSNP:rs104893844)"
FT /evidence="ECO:0000269|PubMed:11318785,
FT ECO:0000269|PubMed:11994356"
FT /id="VAR_019312"
FT VARIANT 106
FT /note="Q -> R (in HH7; some patients also carry mutations
FT in FGFR1; decreases but does not eliminate GnRH binding;
FT dbSNP:rs104893836)"
FT /evidence="ECO:0000269|PubMed:10022417,
FT ECO:0000269|PubMed:11397842, ECO:0000269|PubMed:11397871,
FT ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900,
FT ECO:0000269|PubMed:9371856"
FT /id="VAR_019313"
FT VARIANT 129
FT /note="A -> D (in HH7; complete loss of function;
FT dbSNP:rs104893838)"
FT /evidence="ECO:0000269|PubMed:10084584,
FT ECO:0000269|PubMed:25077900"
FT /id="VAR_019314"
FT VARIANT 139
FT /note="R -> H (in HH7; completely eliminates detectable
FT GnRH-binding activity and prevents GnRH-induced stimulation
FT of inositol phosphate accumulation in vitro;
FT dbSNP:rs104893842)"
FT /evidence="ECO:0000269|PubMed:11397871,
FT ECO:0000269|PubMed:25077900"
FT /id="VAR_019315"
FT VARIANT 146
FT /note="P -> S (in HH7; dbSNP:rs144900788)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072973"
FT VARIANT 168
FT /note="S -> R (in HH7; complete loss of the receptor-
FT mediated signaling response; dbSNP:rs104893840)"
FT /evidence="ECO:0000269|PubMed:10523035"
FT /id="VAR_019316"
FT VARIANT 171
FT /note="A -> T (in HH7; complete loss of ligand binding and
FT receptor activation; specific receptor binding of
FT radioisotope-labeled GnRH ligand is undetectable in
FT transfected cells; dbSNP:rs74452732)"
FT /evidence="ECO:0000269|PubMed:12679486"
FT /id="VAR_019317"
FT VARIANT 217
FT /note="S -> R (in HH7; altered hormone binding;
FT dbSNP:rs104893839)"
FT /evidence="ECO:0000269|PubMed:10022417"
FT /id="VAR_019318"
FT VARIANT 262
FT /note="R -> Q (in HH7; unknown pathological significance;
FT some patients also carry mutations in FGFR1; minimal
FT effects upon receptor affinity but expression decreased;
FT altered activation of phospholipase C; dbSNP:rs104893837)"
FT /evidence="ECO:0000269|PubMed:10022417,
FT ECO:0000269|PubMed:10084584, ECO:0000269|PubMed:23643382,
FT ECO:0000269|PubMed:25077900, ECO:0000269|PubMed:9371856,
FT ECO:0000269|PubMed:9425890"
FT /id="VAR_019319"
FT VARIANT 266
FT /note="L -> R (in HH7; unknown pathological significance;
FT dbSNP:rs148499544)"
FT /evidence="ECO:0000269|PubMed:25077900"
FT /id="VAR_072974"
FT VARIANT 284
FT /note="Y -> C (in HH7; minimal effects upon receptor
FT affinity but receptor expression decreased;
FT dbSNP:rs28933074)"
FT /evidence="ECO:0000269|PubMed:9425890"
FT /id="VAR_019320"
FT CONFLICT 247
FT /note="H -> T (in Ref. 8; CAB17082)"
FT /evidence="ECO:0000305"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 33..62
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 75..99
FT /evidence="ECO:0007829|PDB:7BR3"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 111..141
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 155..170
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:7BR3"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:7BR3"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:7BR3"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 205..217
FT /evidence="ECO:0007829|PDB:7BR3"
FT TURN 218..220
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 221..241
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 260..292
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 294..299
FT /evidence="ECO:0007829|PDB:7BR3"
FT HELIX 302..325
FT /evidence="ECO:0007829|PDB:7BR3"
SQ SEQUENCE 328 AA; 37731 MW; D02B2EA2F4246D7B CRC64;
MANSASPEQN QNHCSAINNS IPLMQGNLPT LTLSGKIRVT VTFFLFLLSA TFNASFLLKL
QKWTQKKEKG KKLSRMKLLL KHLTLANLLE TLIVMPLDGM WNITVQWYAG ELLCKVLSYL
KLFSMYAPAF MMVVISLDRS LAITRPLALK SNSKVGQSMV GLAWILSSVF AGPQLYIFRM
IHLADSSGQT KVFSQCVTHC SFSQWWHQAF YNFFTFSCLF IIPLFIMLIC NAKIIFTLTR
VLHQDPHELQ LNQSKNNIPR ARLKTLKMTV AFATSFTVCW TPYYVLGIWY WFDPEMLNRL
SDPVNHFFFL FAFLNPCFDP LIYGYFSL
