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 27-MAR-2024, entry version 210. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; DB17083; Linzagolix. 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 GlyCosmos; P30968; 2 sites, No reported glycans. DR GlyGen; P30968; 2 sites. DR PhosphoSitePlus; P30968; -. DR BioMuta; GNRHR; -. DR DMDM; 399777; -. DR EPD; P30968; -. DR MassIVE; P30968; -. DR PaxDb; 9606-ENSP00000226413; -. DR PeptideAtlas; P30968; -. DR ABCD; P30968; 2 sequenced antibodies. DR Antibodypedia; 12675; 517 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 AGR; HGNC:4421; -. DR CTD; 2798; -. DR DisGeNET; 2798; -. DR GeneCards; GNRHR; -. DR GeneReviews; GNRHR; -. DR HGNC; HGNC:4421; GNRHR. DR HPA; ENSG00000109163; Tissue enriched (pituitary). 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; LHQDPHE; -. DR OrthoDB; 4815971at2759; -. 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 1147 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 82 other cell types or tissues. DR GO; GO:0016020; C:membrane; TAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB. 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:0032870; P:cellular response to hormone stimulus; 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 Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR001658; GphnRH_fam_rcpt. DR PANTHER; PTHR24241:SF22; GONADOTROPIN-RELEASING HORMONE RECEPTOR; 1. DR PANTHER; PTHR24241; NEUROPEPTIDE RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00529; GNADOTRPHINR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P30968; HS. 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 FT receptor-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; uncertain significance; some FT patients also carry mutations in FGFR1; minimal effects FT upon receptor affinity but expression decreased; altered FT 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; uncertain 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 //