ID PKR2_HUMAN Reviewed; 384 AA. AC Q8NFJ6; A5JUU1; Q2M3C0; Q5TDY1; Q9NTT0; DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Prokineticin receptor 2; DE Short=PK-R2; DE AltName: Full=G-protein coupled receptor 73-like 1; DE AltName: Full=G-protein coupled receptor I5E; DE AltName: Full=GPR73b; DE AltName: Full=GPRg2; GN Name=PROKR2; Synonyms=GPR73L1, PKR2; 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]. RX PubMed=11886876; DOI=10.1074/jbc.m202139200; RA Lin D.C.-H., Bullock C.M., Ehlert F.J., Chen J.-L., Tian H., Zhou Q.-Y.; RT "Identification and molecular characterization of two closely related G RT protein-coupled receptors activated by prokineticins/endocrine gland RT vascular endothelial growth factor."; RL J. Biol. Chem. 277:19276-19280(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12427552; DOI=10.1016/s0167-4781(02)00546-8; RA Soga T., Matsumoto S., Oda T., Saito T., Hiyama H., Takasaki J., RA Kamohara M., Ohishi T., Matsushime H., Furuichi K.; RT "Molecular cloning and characterization of prokineticin receptors."; RL Biochim. Biophys. Acta 1579:173-179(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MET-331. RC TISSUE=Testis; RA Martin A.L., Kaighin V.A., Aronstam R.S.; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [6] RP SUBUNIT. RX PubMed=21161321; DOI=10.1007/s00018-010-0601-6; RA Marsango S., Bonaccorsi di Patti M.C., Barra D., Miele R.; RT "Evidence that prokineticin receptor 2 exists as a dimer in vivo."; RL Cell. Mol. Life Sci. 68:2919-2929(2011). RN [7] RP VARIANTS HH3 CYS-85; HIS-85; GLN-164; ARG-173; SER-178; ARG-210; CYS-268; RP SER-290; ILE-323 AND MET-331, AND VARIANT MET-335. RX PubMed=17054399; DOI=10.1371/journal.pgen.0020175; RA Dode C., Teixeira L., Levilliers J., Fouveaut C., Bouchard P., RA Kottler M.-L., Lespinasse J., Lienhardt-Roussie A., Mathieu M., Moerman A., RA Morgan G., Murat A., Toublanc J.-E., Wolczynski S., Delpech M., Petit C., RA Young J., Hardelin J.-P.; RT "Kallmann syndrome: mutations in the genes encoding prokineticin-2 and RT prokineticin receptor-2."; RL PLoS Genet. 2:1648-1652(2006). RN [8] RP VARIANTS HH3 CYS-85; HIS-113; MET-115; GLN-164; ARG-173; SER-178; LEU-188; RP GLN-248; MET-331 AND TRP-357, AND CHARACTERIZATION OF VARIANTS HH3 CYS-85; RP HIS-113; MET-115; GLN-164; ARG-173; SER-178; LEU-188; GLN-248; MET-331 AND RP TRP-357. RX PubMed=18559922; DOI=10.1210/jc.2007-2654; RA Cole L.W., Sidis Y., Zhang C., Quinton R., Plummer L., Pignatelli D., RA Hughes V.A., Dwyer A.A., Raivio T., Hayes F.J., Seminara S.B., Huot C., RA Alos N., Speiser P., Takeshita A., Van Vliet G., Pearce S., RA Crowley W.F. Jr., Zhou Q.Y., Pitteloud N.; RT "Mutations in prokineticin 2 and prokineticin receptor 2 genes in human RT gonadotrophin-releasing hormone deficiency: molecular genetics and clinical RT spectrum."; RL J. Clin. Endocrinol. Metab. 93:3551-3559(2008). RN [9] RP CHARACTERIZATION OF VARIANTS HH3 CYS-85; HIS-85; GLN-164; ARG-173; SER-178; RP ARG-210; CYS-268; SER-290; ILE-323 AND MET-331, AND SUBCELLULAR LOCATION. RX PubMed=18826963; DOI=10.1093/hmg/ddn318; RA Monnier C., Dode C., Fabre L., Teixeira L., Labesse G., Pin J.P., RA Hardelin J.P., Rondard P.; RT "PROKR2 missense mutations associated with Kallmann syndrome impair RT receptor signalling activity."; RL Hum. Mol. Genet. 18:75-81(2009). RN [10] RP VARIANT HH3 CYS-268. RX PubMed=22927827; DOI=10.1371/journal.pgen.1002896; RA Hanchate N.K., Giacobini P., Lhuillier P., Parkash J., Espy C., RA Fouveaut C., Leroy C., Baron S., Campagne C., Vanacker C., Collier F., RA Cruaud C., Meyer V., Garcia-Pinero A., Dewailly D., Cortet-Rudelli C., RA Gersak K., Metz C., Chabrier G., Pugeat M., Young J., Hardelin J.P., RA Prevot V., Dode C.; RT "SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with RT Kallmann syndrome."; RL PLoS Genet. 8:E1002896-E1002896(2012). RN [11] RP VARIANTS HH3 MET-115 AND GLY-202. 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 [12] RP VARIANTS HH3 CYS-85; HIS-85; ILE-158; ARG-173; SER-290 AND MET-334. 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). RN [13] RP VARIANT HH3 HIS-113. RX PubMed=28858133; DOI=10.1097/md.0000000000007974; RA Ha J.H., Lee S., Kim Y., Moon J.I., Seo J., Jang J.H., Cho E.H., Kim J.M., RA Rhee B.D., Ko K.S., Yoo S.J., Won J.C.; RT "Kallmann syndrome with a Tyr113His PROKR2 mutation."; RL Medicine (Baltimore) 96:E7974-E7974(2017). CC -!- FUNCTION: Receptor for prokineticin 2. Exclusively coupled to the G(q) CC subclass of heteromeric G proteins. Activation leads to mobilization of CC calcium, stimulation of phosphoinositide turnover and activation of CC p44/p42 mitogen-activated protein kinase. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21161321}. CC -!- INTERACTION: CC Q8NFJ6; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-12902928, EBI-10827839; CC Q8NFJ6; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-12902928, EBI-12142257; CC Q8NFJ6; P48165: GJA8; NbExp=3; IntAct=EBI-12902928, EBI-17458373; CC Q8NFJ6; P24593: IGFBP5; NbExp=3; IntAct=EBI-12902928, EBI-720480; CC Q8NFJ6; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-12902928, EBI-988826; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18826963}; CC Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in the ileocecum, thyroid gland, CC pituitary gland, salivary gland, adrenal gland, testis, ovary and CC brain. CC -!- DISEASE: Hypogonadotropic hypogonadism 3 with or without anosmia (HH3) CC [MIM:244200]: 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:17054399, ECO:0000269|PubMed:18559922, CC ECO:0000269|PubMed:18826963, ECO:0000269|PubMed:22927827, CC ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900}. 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 PROKR2 as well as in other HH-associated genes including CC KAL1, SEMA3A, PROK2, GNRH1 and FGFR1 (PubMed:17054399, PubMed:22927827, CC PubMed:23643382). {ECO:0000269|PubMed:17054399, CC ECO:0000269|PubMed:22927827, ECO:0000269|PubMed:23643382, CC ECO:0000269|PubMed:28858133}. 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; AF506288; AAM48128.1; -; mRNA. DR EMBL; AB084081; BAC24022.1; -; mRNA. DR EMBL; EF577398; ABQ52418.1; -; mRNA. DR EMBL; AL121755; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC104959; AAI04960.1; -; mRNA. DR EMBL; BC104961; AAI04962.1; -; mRNA. DR CCDS; CCDS13089.1; -. DR RefSeq; NP_658986.1; NM_144773.3. DR RefSeq; XP_016883135.1; XM_017027646.1. DR AlphaFoldDB; Q8NFJ6; -. DR SMR; Q8NFJ6; -. DR BioGRID; 126143; 7. DR IntAct; Q8NFJ6; 5. DR STRING; 9606.ENSP00000217270; -. DR BindingDB; Q8NFJ6; -. DR ChEMBL; CHEMBL5548; -. DR GuidetoPHARMACOLOGY; 336; -. DR GlyCosmos; Q8NFJ6; 2 sites, No reported glycans. DR GlyGen; Q8NFJ6; 2 sites. DR iPTMnet; Q8NFJ6; -. DR PhosphoSitePlus; Q8NFJ6; -. DR BioMuta; PROKR2; -. DR DMDM; 33112425; -. DR MassIVE; Q8NFJ6; -. DR PaxDb; 9606-ENSP00000217270; -. DR PeptideAtlas; Q8NFJ6; -. DR ProteomicsDB; 73317; -. DR Antibodypedia; 8176; 272 antibodies from 33 providers. DR DNASU; 128674; -. DR Ensembl; ENST00000217270.4; ENSP00000217270.3; ENSG00000101292.8. DR Ensembl; ENST00000678254.1; ENSP00000504128.1; ENSG00000101292.8. DR GeneID; 128674; -. DR KEGG; hsa:128674; -. DR MANE-Select; ENST00000678254.1; ENSP00000504128.1; NM_144773.4; NP_658986.1. DR UCSC; uc010zqw.3; human. DR AGR; HGNC:15836; -. DR CTD; 128674; -. DR DisGeNET; 128674; -. DR GeneCards; PROKR2; -. DR GeneReviews; PROKR2; -. DR HGNC; HGNC:15836; PROKR2. DR HPA; ENSG00000101292; Tissue enhanced (brain). DR MalaCards; PROKR2; -. DR MIM; 244200; phenotype. DR MIM; 607123; gene. DR neXtProt; NX_Q8NFJ6; -. DR OpenTargets; ENSG00000101292; -. DR Orphanet; 478; Kallmann syndrome. DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism. DR Orphanet; 95496; Pituitary stalk interruption syndrome. DR Orphanet; 3157; Septo-optic dysplasia spectrum. DR PharmGKB; PA30014; -. DR VEuPathDB; HostDB:ENSG00000101292; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000154544; -. DR HOGENOM; CLU_009579_6_0_1; -. DR InParanoid; Q8NFJ6; -. DR OMA; FPFNFTY; -. DR OrthoDB; 4111530at2759; -. DR PhylomeDB; Q8NFJ6; -. DR TreeFam; TF315303; -. DR PathwayCommons; Q8NFJ6; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; Q8NFJ6; -. DR SIGNOR; Q8NFJ6; -. DR BioGRID-ORCS; 128674; 19 hits in 1145 CRISPR screens. DR GeneWiki; Prokineticin_receptor_2; -. DR GenomeRNAi; 128674; -. DR Pharos; Q8NFJ6; Tchem. DR PRO; PR:Q8NFJ6; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q8NFJ6; Protein. DR Bgee; ENSG00000101292; Expressed in cortical plate and 20 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0004983; F:neuropeptide Y receptor activity; IEA:InterPro. DR GO; GO:0007623; P:circadian rhythm; IBA:GO_Central. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR CDD; cd15204; 7tmA_prokineticin-R; 1. 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; IPR000611; NPY_rcpt. DR PANTHER; PTHR24238; G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24238:SF71; PROKINETICIN RECEPTOR 2; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01012; NRPEPTIDEYR. 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; Q8NFJ6; HS. PE 1: Evidence at protein level; KW Cell membrane; Disease variant; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Hypogonadotropic hypogonadism; Kallmann syndrome; Membrane; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..384 FT /note="Prokineticin receptor 2" FT /id="PRO_0000070083" FT TOPO_DOM 1..54 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 55..75 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 76..89 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 90..110 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 111..136 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 137..157 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 158..171 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 172..192 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 193..223 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 224..244 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 245..273 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 274..294 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 295..313 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 314..334 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 335..384 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 7 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 27 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 128..208 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VARIANT 85 FT /note="R -> C (in HH3; phenotype consistent with normosmic FT idiopathic hypogonadotropic hypogonadism; decreased FT signaling activity; dbSNP:rs141090506)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18559922, ECO:0000269|PubMed:18826963, FT ECO:0000269|PubMed:25077900" FT /id="VAR_030957" FT VARIANT 85 FT /note="R -> H (in HH3; decreased signaling activity; FT dbSNP:rs74315418)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18826963, ECO:0000269|PubMed:25077900" FT /id="VAR_030958" FT VARIANT 113 FT /note="Y -> H (in HH3; dbSNP:rs202203360)" FT /evidence="ECO:0000269|PubMed:18559922, FT ECO:0000269|PubMed:28858133" FT /id="VAR_072173" FT VARIANT 115 FT /note="V -> M (in HH3; phenotype consistent with Kallmann FT syndrome; dbSNP:rs138672528)" FT /evidence="ECO:0000269|PubMed:18559922, FT ECO:0000269|PubMed:23643382" FT /id="VAR_069964" FT VARIANT 158 FT /note="V -> I (in HH3; phenotype consistent with Kallmann FT syndrome; dbSNP:rs368732206)" FT /evidence="ECO:0000269|PubMed:25077900" FT /id="VAR_072978" FT VARIANT 164 FT /note="R -> Q (in HH3; phenotype consistent with Kallmann FT syndrome; decreased signaling activity; dbSNP:rs751875578)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18559922, ECO:0000269|PubMed:18826963" FT /id="VAR_030959" FT VARIANT 173 FT /note="L -> R (in HH3; phenotype consistent with Kallmann FT syndrome; decreased signaling activity; dbSNP:rs74315416)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18559922, ECO:0000269|PubMed:18826963, FT ECO:0000269|PubMed:25077900" FT /id="VAR_030960" FT VARIANT 178 FT /note="W -> S (in HH3; decreased signaling activity; FT dbSNP:rs201835496)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18559922, ECO:0000269|PubMed:18826963" FT /id="VAR_030961" FT VARIANT 188 FT /note="S -> L (in HH3; dbSNP:rs376239580)" FT /evidence="ECO:0000269|PubMed:18559922" FT /id="VAR_072174" FT VARIANT 202 FT /note="S -> G (in HH3; triallelic inheritance; the patient FT also carries mutations in GNRH1 and FGFR1; FT dbSNP:rs200755554)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069965" FT VARIANT 210 FT /note="Q -> R (in HH3; phenotype consistent with Kallmann FT syndrome; decreased signaling activity; abolished ligand FT binding; dbSNP:rs74315417)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18826963" FT /id="VAR_030962" FT VARIANT 248 FT /note="R -> Q (in HH3; dbSNP:rs376142095)" FT /evidence="ECO:0000269|PubMed:18559922" FT /id="VAR_072175" FT VARIANT 268 FT /note="R -> C (in HH3; benign; signaling activity is FT impaired; dbSNP:rs78861628)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18826963, ECO:0000269|PubMed:22927827" FT /id="VAR_030963" FT VARIANT 290 FT /note="P -> S (in HH3; phenotype consistent with Kallmann FT syndrome; signaling activity is impaired; impaired cell FT surface-targeting; dbSNP:rs149992595)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18826963, ECO:0000269|PubMed:25077900" FT /id="VAR_030964" FT VARIANT 323 FT /note="M -> I (in HH3; phenotype consistent with Kallmann FT syndrome; signaling activity is impaired; FT dbSNP:rs74315419)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18826963" FT /id="VAR_030965" FT VARIANT 331 FT /note="V -> M (in HH3; likely benign; dbSNP:rs117106081)" FT /evidence="ECO:0000269|PubMed:17054399, FT ECO:0000269|PubMed:18559922, ECO:0000269|PubMed:18826963, FT ECO:0000269|Ref.3" FT /id="VAR_030966" FT VARIANT 334 FT /note="V -> M (in HH3; phenotype consistent with Kallmann FT syndrome; dbSNP:rs371564610)" FT /evidence="ECO:0000269|PubMed:25077900" FT /id="VAR_072979" FT VARIANT 335 FT /note="T -> M (in dbSNP:rs755562438)" FT /evidence="ECO:0000269|PubMed:17054399" FT /id="VAR_030967" FT VARIANT 357 FT /note="R -> W (in HH3; dbSNP:rs375036628)" FT /evidence="ECO:0000269|PubMed:18559922" FT /id="VAR_072176" SQ SEQUENCE 384 AA; 43996 MW; 2D5BFA3655347B5E CRC64; MAAQNGNTSF TPNFNPPQDH ASSLSFNFSY GDYDLPMDED EDMTKTRTFF AAKIVIGIAL AGIMLVCGIG NFVFIAALTR YKKLRNLTNL LIANLAISDF LVAIICCPFE MDYYVVRQLS WEHGHVLCAS VNYLRTVSLY VSTNALLAIA IDRYLAIVHP LKPRMNYQTA SFLIALVWMV SILIAIPSAY FATETVLFIV KSQEKIFCGQ IWPVDQQLYY KSYFLFIFGV EFVGPVVTMT LCYARISREL WFKAVPGFQT EQIRKRLRCR RKTVLVLMCI LTAYVLCWAP FYGFTIVRDF FPTVFVKEKH YLTAFYVVEC IAMSNSMINT VCFVTVKNNT MKYFKKMMLL HWRPSQRGSK SSADLDLRTN GVPTTEEVDC IRLK //