PKR2_HUMAN
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 03-AUG-2022, entry version 166.
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}.
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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; 6.
DR IntAct; Q8NFJ6; 5.
DR STRING; 9606.ENSP00000217270; -.
DR BindingDB; Q8NFJ6; -.
DR ChEMBL; CHEMBL5548; -.
DR GuidetoPHARMACOLOGY; 336; -.
DR GlyGen; Q8NFJ6; 2 sites.
DR iPTMnet; Q8NFJ6; -.
DR PhosphoSitePlus; Q8NFJ6; -.
DR BioMuta; PROKR2; -.
DR DMDM; 33112425; -.
DR MassIVE; Q8NFJ6; -.
DR PaxDb; Q8NFJ6; -.
DR PRIDE; Q8NFJ6; -.
DR Antibodypedia; 8176; 245 antibodies from 32 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 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; VDCIKLQ; -.
DR OrthoDB; 664455at2759; -.
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; 18 hits in 1069 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 tissues.
DR Genevisible; Q8NFJ6; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000611; NPY_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01012; NRPEPTIDEYR.
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 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 variant; signaling activity
FT is 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 variant;
FT 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
