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Entry
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- *603286 - KISS1 METASTASIS SUPPRESSOR; KISS1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*603286</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603286">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000170498;t=ENST00000367194" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=3814" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603286" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000170498;t=ENST00000367194" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_002256" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_002256" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=603286" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
|
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=04475&isoform_id=04475_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/KISS1" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/2347058,10441964,21950714,22137579,116829964,119611912,119611913,158256822,261385435,292495092,2703608606" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q15726" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=3814" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000170498;t=ENST00000367194" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=KISS1" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=KISS1" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+3814" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/KISS1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:3814" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3814" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000367194.5&hgg_start=204190341&hgg_end=204196491&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:6341" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603286[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603286[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000170498" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=KISS1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=KISS1" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=KISS1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=KISS1&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA30127" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:6341" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2663985" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/KISS1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:2663985" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3814/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002619/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3814" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-080128-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3814" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=KISS1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603286
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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KISS1 METASTASIS SUPPRESSOR; KISS1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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METASTIN<br />
|
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KISSPEPTIN
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=KISS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KISS1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/1/1607?start=-3&limit=10&highlight=1607">1q32.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:204190341-204196491&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:204,190,341-204,196,491</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/1/1607?start=-3&limit=10&highlight=1607">
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1q32.1
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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?Hypogonadotropic hypogonadism 13 with or without anosmia
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<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
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</span>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/614842"> 614842 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/603286" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603286" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
|
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</h4>
|
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<div class="mim-changed mim-change"><p>KISS1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, called kisspeptins, which act through the G protein-coupled receptor GPR54 (KISS1R; <a href="/entry/604161">604161</a>). KISS1 has a role in the neuroendocrine control of gonadotropin secretion (summary by <a href="#7" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15375028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<div class="mim-changed mim-change"><p><a href="#14" class="mim-tip-reference" title="Welch, D. R., Chen, P., Miele, M. E., McGary, C. T., Bower, J. M., Stanbridge, E. J., Weissman, B. E. <strong>Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity.</strong> Oncogene 9: 255-262, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8302587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8302587</a>]" pmid="8302587">Welch et al. (1994)</a> found that microcell-mediated transfer of human chromosome 6 into human metastatic melanoma cells (C8161 or MelJuSo) suppressed their ability to metastasize in athymic nude mice by at least 95% without affecting the tumorigenicity of the cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8302587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<div class="mim-changed mim-change"><p>Using a modified subtractive hybridization approach, <a href="#5" class="mim-tip-reference" title="Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R. <strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong> J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>] [<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944003">Lee et al. (1996)</a> isolated a cDNA expressed in hybrid chromosome 6-C8161 cells but not in parental C8161 cells. They designated the cDNA KISS1, combining laboratory nomenclature for putative suppressor sequences with acknowledgment of the gene's discovery in Hershey, Pennsylvania. <a href="#5" class="mim-tip-reference" title="Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R. <strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong> J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>] [<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944003">Lee et al. (1996)</a> reported the sequence of the predicted KISS1 protein and a corrected sequence in a published erratum. The KISS1 protein consists of 145 amino acids. Northern blot analysis revealed that KISS1 was expressed as a 1-kb mRNA in chromosome 6-C8161 hybrid cell lines as well as in normal placenta tissue. Low levels of smaller transcripts were observed in pancreas and kidney. <a href="#5" class="mim-tip-reference" title="Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R. <strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong> J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>] [<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944003">Lee et al. (1996)</a> did not detect KISS1 expression in any cell line capable of metastasizing in athymic nude mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<div class="mim-changed mim-change"><p><a href="#9" class="mim-tip-reference" title="Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others. <strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong> Nature 411: 613-617, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385580</a>] [<a href="https://doi.org/10.1038/35079135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11385580">Ohtaki et al. (2001)</a> demonstrated that KISS1 encodes a carboxy-terminally amidated peptide with 54 amino acid residues, which the authors isolated from human placenta as the endogenous ligand of an orphan G protein-coupled receptor (GPR54; <a href="/entry/604161">604161</a>). They named the truncated form of KISS1 'metastin.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<p>By fluorescence in situ hybridization (FISH), <a href="#5" class="mim-tip-reference" title="Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R. <strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong> J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>] [<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944003">Lee et al. (1996)</a> mapped the KISS1 gene to 1q32-q41. They suggested that a metastasis-suppressing gene or genes on chromosome 6 regulate KISS1. By radiation hybrid mapping and FISH, <a href="#15" class="mim-tip-reference" title="West, A., Vojta, P. J., Welch, D. R., Weissman, B. E. <strong>Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1).</strong> Genomics 54: 145-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806840</a>] [<a href="https://doi.org/10.1006/geno.1998.5566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9806840">West et al. (1998)</a> localized the KISS1 gene to 1q32. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9806840+8944003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R. <strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong> J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>] [<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8944003">Lee et al. (1996)</a> observed that expression of KISS1 in C8161 melanoma cells suppressed metastasis, suggesting that KISS1 plays a role in the regulation of cancer metastasis in human malignant melanoma. <a href="#6" class="mim-tip-reference" title="Lee, J.-H., Welch, D. R. <strong>Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1.</strong> Cancer Res. 57: 2384-2387, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192814</a>]" pmid="9192814">Lee and Welch (1997)</a> demonstrated that expression of KISS1 in human breast carcinoma cells reduced metastatic potential by 95% compared to control cells but did not suppress tumorigenicity. The authors concluded that KISS1 also functions as a metastasis suppressor gene in at least some human breast cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9192814+8944003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#9" class="mim-tip-reference" title="Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others. <strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong> Nature 411: 613-617, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385580</a>] [<a href="https://doi.org/10.1038/35079135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11385580">Ohtaki et al. (2001)</a> found that metastin inhibited chemotaxis and invasion of GPR54-transfected CHO cells in vitro and attenuated pulmonary metastasis of GPR54-transfected B16-BL6 melanomas in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<p>Using real-time PCR, <a href="#10" class="mim-tip-reference" title="Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M. <strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong> Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0409822102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15684075">Shahab et al. (2005)</a> found that expression of Kiss1 mRNA increased with puberty in both male and female rhesus monkeys. Kisspeptin-10 (112-121), a decapeptide derived from KISS1, was administered to agonadal juvenile monkeys and induced a GnRH (<a href="/entry/152760">152760</a>) response as measured by a surge in plasma luteinizing hormone (LH; see <a href="/entry/152780">152780</a>). In intact females, but not in agonadal males, the level of Gpr54 mRNA in the hypothalamus increased about 3-fold from the juvenile to midpubertal stage. In situ hybridization detected robust Kiss1 and Gpr54 expression in the arcuate nucleus. <a href="#10" class="mim-tip-reference" title="Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M. <strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong> Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0409822102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15684075">Shahab et al. (2005)</a> concluded that KISS1 signaling through GPR54 in the primate hypothalamus at the end of the juvenile phase of development may contribute to the pubertal resurgence of pulsatile GnRH release. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15684075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., Maeda, K.-I. <strong>Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats.</strong> Endocrinology 146: 4431-4436, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15976058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15976058</a>] [<a href="https://doi.org/10.1210/en.2005-0195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15976058">Kinoshita et al. (2005)</a> examined whether metastin, the product of metastasis suppressor gene KISS1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Injection of metastin into the third ventricle or preoptic area increased plasma LH concentrations in estrogen-primed ovariectomized rats, demonstrating that metastin profoundly stimulates LH secretion by acting on the preoptic area, where most GnRH neurons projecting to the median eminence are located. Immunohistochemical analysis demonstrated metastin neurons in the arcuate nucleus colocalized with estrogen receptors, with some fibers in the preoptic area in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR revealed KISS1 and GPR54 (<a href="/entry/606161">606161</a>) mRNAs expressed in the arcuate nucleus and preoptic area, respectively. The blockade of local metastin action in the preoptic area with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. In the arcuate nucleus, numbers of metastin-immunoreactive cell bodies and c-Fos (<a href="/entry/164810">164810</a>) expression were significantly higher in the early proestrus afternoon compared with the day of diestrus. Thus, <a href="#4" class="mim-tip-reference" title="Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., Maeda, K.-I. <strong>Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats.</strong> Endocrinology 146: 4431-4436, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15976058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15976058</a>] [<a href="https://doi.org/10.1210/en.2005-0195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15976058">Kinoshita et al. (2005)</a> concluded that metastin released in the preoptic area is involved in inducing the preovulatory LH surge and regulating estrous cyclicity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15976058" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> studied the effect of KISS1 peptide on LH secretion using in vitro and in vivo settings under different experimental conditions. Central intracerebroventricular administration of KISS1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KISS1 appeared to be mediated via the hypothalamic LHRH. However, no effect of central administration of KISS1 was detected on relative LHRH mRNA levels. Likewise, systemic (either intraperitoneal or intravascular) injection of KISS1 markedly stimulated LH secretion. <a href="#7" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> found that LH-releasing activity of KISS1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e., relevant neurotransmitters in the neuroendocrine control of LH secretion. <a href="#7" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong> Endocrinology 146: 156-163, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>] [<a href="https://doi.org/10.1210/en.2004-0836" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15375028">Navarro et al. (2005)</a> concluded that their results provided solid evidence for a potent stimulatory effect of KISS1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further documented a novel role of the KISS1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15375028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., Steiner, R. A. <strong>Regulation of Kiss1 gene expression in the brain of the female mouse.</strong> Endocrinology 146: 3686-3692, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15919741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15919741</a>] [<a href="https://doi.org/10.1210/en.2005-0488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15919741">Smith et al. (2005)</a> found that KISS1 neurons in the arcuate nucleus, which are inhibited by estradiol, may play a role in the negative feedback regulation of GnRH secretion, whereas KISS1 neurons in the anteroventral periventricular nucleus, which are stimulated by estradiol, may participate in the positive feedback regulation of GnRH secretion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15919741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Road, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.</strong> Endocrinology 146: 1689-1697, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637288</a>] [<a href="https://doi.org/10.1210/en.2004-1353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637288">Navarro et al. (2005)</a> studied the effects of KISS1 peptide on FSH (see <a href="/entry/136530">136530</a>) secretion in vivo and in vitro. Intracerebroventricular administration of KISS1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED50 value for the FSH-releasing effects of KISS1 of 400 pmol, i.e., approximately 100-fold higher than that of LH. In addition, systemic injection of KISS1 significantly stimulated FSH secretion in vivo. However, KISS1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, <a href="#8" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Road, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.</strong> Endocrinology 146: 1689-1697, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637288</a>] [<a href="https://doi.org/10.1210/en.2004-1353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637288">Navarro et al. (2005)</a> reported that mechanistic studies revealed that the ability of KISS1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin (<a href="/entry/164160">164160</a>) insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, <a href="#8" class="mim-tip-reference" title="Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Road, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M. <strong>Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.</strong> Endocrinology 146: 1689-1697, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637288</a>] [<a href="https://doi.org/10.1210/en.2004-1353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15637288">Navarro et al. (2005)</a> concluded that their results extended previous observations on the role of KISS1 in the control of LH secretion and provided solid evidence for a stimulatory effect of KISS1 on FSH release, acting at a central level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a study of 6 healthy male volunteers, <a href="#3" class="mim-tip-reference" title="Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R. <strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong> J. Clin. Endocr. Metab. 90: 6609-6615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>] [<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174713">Dhillo et al. (2005)</a> found that elevation of plasma concentrations of kisspeptin significantly increased circulating LH, FSH, and testosterone levels. <a href="#3" class="mim-tip-reference" title="Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R. <strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong> J. Clin. Endocr. Metab. 90: 6609-6615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>] [<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16174713">Dhillo et al. (2005)</a> suggested that kisspeptin infusion may provide a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16174713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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In a consanguineous Kurdish family in which 4 sisters had normosmic hypogonadotropic hypogonadism (HH13; <a href="/entry/614842">614842</a>), <a href="#13" class="mim-tip-reference" title="Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., Yuksel, B. <strong>Inactivating KISS1 mutation and hypogonadotropic hypogonadism.</strong> New Eng. J. Med. 366: 629-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22335740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22335740</a>] [<a href="https://doi.org/10.1056/NEJMoa1111184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22335740">Topaloglu et al. (2012)</a> identified homozygosity for a missense mutation in the KISS1 gene (<a href="#0001">603286.0001</a>) that segregated with the disease and was not found in 100 ethnically matched controls. Subsequent analysis of KISS1 in 12 additional families with normosmic hypogonadotropic hypogonadism and in 90 sporadic cases revealed no mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22335740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of an association between central precocious puberty (see <a href="/entry/176400">176400</a>) and variation in the KISS1 gene, see <a href="#0002">603286.0002</a>.</p><p>In a cohort of 65 patients with adrenal steroid hypersecretion syndromes, <a href="#1" class="mim-tip-reference" title="Berthon, A., Settas, N., Delaney, A., Giannakou, A., Demidowich, A., Faucz, F. R., Seminara, S. B., Chen, M. E., Stratakis, C. A. <strong>Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.</strong> Hum. Molec. Genet. 29: 3443-3450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33089319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33089319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33089319[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddaa215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33089319">Berthon et al. (2020)</a> analyzed the KISS1 and KISS1R genes and identified 1 patient with primary aldosteronism (see <a href="/entry/103900">103900</a>) and hypercortisolism (see <a href="/entry/610489">610489</a>) who was heterozygous for an H90D variant (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs201073751;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs201073751</a>) in the KISS1 gene. The authors noted that the variant, present in the gnomAD database with a minor allele frequency (MAF) of 0.00137, was relatively frequent in the African population (MAF = 0.022 in Africans). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33089319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P. C., Day, K., Leitch, H. G., Hendrick, A. G., Zahn, D., Franceschini, I., Caraty, A., Carlton, M. B. L., Aparicio, S. A. J. R., Colledge, W. H. <strong>Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.</strong> Proc. Nat. Acad. Sci. 104: 10714-10719, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17563351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17563351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17563351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0704114104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17563351">D'Anglemont de Tassigny et al. (2007)</a> generated Kiss1-null mice that were viable and healthy with no apparent abnormalities but failed to undergo sexual maturation. Mutant female mice did not progress through the estrous cycle, had thread-like uteri and small ovaries, and did not produce mature Graffian follicles. Mutant males had small testes, and spermatogenesis arrested mainly at the early haploid spermatid stage. Both sexes had low circulating gonadotropin (LH and FSH) and sex steroid (beta-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appeared normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic-pituitary axis was functional, as shown by robust LH secretion after peripheral administration of kisspeptin. <a href="#2" class="mim-tip-reference" title="d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P. C., Day, K., Leitch, H. G., Hendrick, A. G., Zahn, D., Franceschini, I., Caraty, A., Carlton, M. B. L., Aparicio, S. A. J. R., Colledge, W. H. <strong>Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.</strong> Proc. Nat. Acad. Sci. 104: 10714-10719, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17563351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17563351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17563351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0704114104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17563351">D'Anglemont de Tassigny et al. (2007)</a> stated that the phenotypes of Gpr54- and Kiss1-null mice are virtually identical, providing direct proof that kisspeptins are the true physiologic ligand for the GPR54 receptor in vivo. The authors also noted that apart from activation of the hypothalamic-pituitary-gonadal axis, KISS1 does not seem to play a vital role in any other physiologic processes, and loss of KISS1 cannot be overcome by compensatory mechanisms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17563351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In Kiss1 -/- female mice, <a href="#1" class="mim-tip-reference" title="Berthon, A., Settas, N., Delaney, A., Giannakou, A., Demidowich, A., Faucz, F. R., Seminara, S. B., Chen, M. E., Stratakis, C. A. <strong>Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.</strong> Hum. Molec. Genet. 29: 3443-3450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33089319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33089319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33089319[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddaa215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33089319">Berthon et al. (2020)</a> performed histologic analysis of the adrenal glands at 5 months and 12 months of age and observed persistence of the X-zone, a region formed by cells that retain fetal characteristics that normally degenerates after the first pregnancy in female mice and after puberty in males. There was increased expression of X-zone markers, suggesting that the X-zone was expanded in the mutant mice. The authors observed hypercorticosteronism in the female mutants that normalized by 12 months of age; hyperaldosteronism was present in both male and female mutants and persisted at 14 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33089319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0001 HYPOGONADOTROPIC HYPOGONADISM 13 WITHOUT ANOSMIA (1 family)</strong>
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KISS1, ASN115LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777835 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777835;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs587777835?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587777835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs587777835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000030951" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000030951" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000030951</a>
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<p>In 4 affected sisters from a consanguineous Kurdish family with normosmic hypogonadotropic hypogonadism (HH13; <a href="/entry/614842">614842</a>), <a href="#13" class="mim-tip-reference" title="Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., Yuksel, B. <strong>Inactivating KISS1 mutation and hypogonadotropic hypogonadism.</strong> New Eng. J. Med. 366: 629-635, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22335740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22335740</a>] [<a href="https://doi.org/10.1056/NEJMoa1111184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22335740">Topaloglu et al. (2012)</a> identified homozygosity for a 345C-G transversion in the KISS1 gene, resulting in an asn115-to-lys (N115K) substitution at a highly conserved residue. The unaffected parents were heterozygous for the mutation, and unaffected sibs were heterozygous or homozygous for wildtype. The mutation was not found in 100 ethnically matched controls. Functional studies showed that human KISS1R (<a href="/entry/604161">604161</a>) had significantly reduced sensitivity to mutant kisspeptin-10, and mutant kisspeptin-10 was unable to stimulate a maximal inositol phosphate response at any concentration tested, indicating significantly reduced efficacy as well as potency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22335740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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KISS1, PRO74SER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777843 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777843;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs587777843?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587777843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs587777843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000144560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144560</a>
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</span>
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</div>
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<span class="mim-text-font">
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<p>This variant is classified as a variant of unknown significance because its contribution to central precocious puberty (see <a href="/entry/176400">176400</a>) has not been confirmed.</p><p>In a 16-year-old Brazilian boy with central precocious puberty, <a href="#11" class="mim-tip-reference" title="Silveira, L. G., Noel, S. D., Silveira-Neto, A. P., Abreu, A. P., Brito, V. N., Santos, M. G., Bianco, S. D. C., Kuohung, W., Xu, S., Gryngarten, M., Escobar, M. E., Arnhold, I. J. P., Mendonca, B. B., Kaiser, U. B., Latronico, A. C. <strong>Mutations of the KISS1 gene in disorders of puberty.</strong> J. Clin. Endocr. Metab. 95: 2276-2280, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20237166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20237166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20237166[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2009-2421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20237166">Silveira et al. (2010)</a> sequenced the 3 exons of the KISS1 gene and identified heterozygosity for a c.369C-T transition in exon 3, resulting in a pro74-to-ser (P74S) substitution at a highly conserved residue within a PEST sequence in the amino-terminal region. The mutation was also detected in heterozygosity in the patient's unaffected mother and maternal grandmother, who both had menarche at appropriate ages, but was not found in 400 control alleles. Functional analysis in CHO cells showed that the capacity of the mutant to stimulate inositol phosphate production was similar to that of wildtype; however, after incubation in human serum, the capacity to stimulate signal transduction was significantly greater with the mutant than with wildtype KISS1, suggesting that the P74S variant is more stable. The proband underwent pubertal development at 1 year of age, with enlargement of the penis and testes, Tanner stage III pubic hair, bone age of 3 years, and elevated levels of follicle-stimulating hormone, luteinizing hormone, and testosterone. He had no neurologic symptoms, and brain MRI was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20237166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="Berthon2020" class="mim-anchor"></a>
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Berthon, A., Settas, N., Delaney, A., Giannakou, A., Demidowich, A., Faucz, F. R., Seminara, S. B., Chen, M. E., Stratakis, C. A.
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<strong>Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.</strong>
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Hum. Molec. Genet. 29: 3443-3450, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33089319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33089319</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33089319[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33089319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddaa215" target="_blank">Full Text</a>]
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<a id="d'Anglemont de Tassigny2007" class="mim-anchor"></a>
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d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P. C., Day, K., Leitch, H. G., Hendrick, A. G., Zahn, D., Franceschini, I., Caraty, A., Carlton, M. B. L., Aparicio, S. A. J. R., Colledge, W. H.
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<strong>Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.</strong>
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Proc. Nat. Acad. Sci. 104: 10714-10719, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17563351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17563351</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17563351[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17563351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0704114104" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Dhillo2005" class="mim-anchor"></a>
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<div class="">
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Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R.
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<strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong>
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J. Clin. Endocr. Metab. 90: 6609-6615, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16174713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16174713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16174713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jc.2005-1468" target="_blank">Full Text</a>]
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<a id="Kinoshita2005" class="mim-anchor"></a>
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Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., Maeda, K.-I.
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<strong>Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats.</strong>
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Endocrinology 146: 4431-4436, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15976058/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15976058</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15976058" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/en.2005-0195" target="_blank">Full Text</a>]
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<a id="Lee1996" class="mim-anchor"></a>
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Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R.
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<strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong>
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J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8944003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8944003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8944003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/jnci/88.23.1731" target="_blank">Full Text</a>]
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<a id="Lee1997" class="mim-anchor"></a>
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Lee, J.-H., Welch, D. R.
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<strong>Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1.</strong>
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Cancer Res. 57: 2384-2387, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9192814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9192814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9192814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Navarro2005" class="mim-anchor"></a>
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Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
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<strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong>
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Endocrinology 146: 156-163, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15375028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15375028</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15375028" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/en.2004-0836" target="_blank">Full Text</a>]
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<a id="Navarro2005" class="mim-anchor"></a>
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Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Road, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
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<strong>Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.</strong>
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Endocrinology 146: 1689-1697, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15637288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15637288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15637288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/en.2004-1353" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Ohtaki2001" class="mim-anchor"></a>
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Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others.
|
|
<strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong>
|
|
Nature 411: 613-617, 2001.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11385580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11385580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11385580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/35079135" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Shahab2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M.
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<strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong>
|
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Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15684075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15684075</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15684075[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15684075" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0409822102" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Silveira2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Silveira, L. G., Noel, S. D., Silveira-Neto, A. P., Abreu, A. P., Brito, V. N., Santos, M. G., Bianco, S. D. C., Kuohung, W., Xu, S., Gryngarten, M., Escobar, M. E., Arnhold, I. J. P., Mendonca, B. B., Kaiser, U. B., Latronico, A. C.
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<strong>Mutations of the KISS1 gene in disorders of puberty.</strong>
|
|
J. Clin. Endocr. Metab. 95: 2276-2280, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20237166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20237166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20237166[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20237166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jc.2009-2421" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Smith2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., Steiner, R. A.
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<strong>Regulation of Kiss1 gene expression in the brain of the female mouse.</strong>
|
|
Endocrinology 146: 3686-3692, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15919741/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15919741</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15919741" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/en.2005-0488" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Topaloglu2012" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., Yuksel, B.
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<strong>Inactivating KISS1 mutation and hypogonadotropic hypogonadism.</strong>
|
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New Eng. J. Med. 366: 629-635, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22335740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22335740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22335740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1111184" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Welch1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Welch, D. R., Chen, P., Miele, M. E., McGary, C. T., Bower, J. M., Stanbridge, E. J., Weissman, B. E.
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<strong>Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity.</strong>
|
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Oncogene 9: 255-262, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8302587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8302587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8302587" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="West1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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West, A., Vojta, P. J., Welch, D. R., Weissman, B. E.
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<strong>Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1).</strong>
|
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Genomics 54: 145-148, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9806840/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9806840</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9806840" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1998.5566" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 02/17/2022
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</span>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 10/10/2014<br>Marla J. F. O'Neill - updated : 2/23/2012<br>Marla J. F. O'Neill - updated : 7/10/2007<br>John A. Phillips, III - updated : 3/19/2007<br>Ada Hamosh - updated : 11/28/2006<br>Patricia A. Hartz - updated : 6/8/2005<br>Ada Hamosh - updated : 6/14/2001<br>Carol A. Bocchini - updated : 12/11/1998
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</span>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Rebekah S. Rasooly : 11/13/1998
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 02/21/2025
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 02/17/2022<br>carol : 10/15/2014<br>mcolton : 10/14/2014<br>mcolton : 10/10/2014<br>carol : 10/3/2012<br>carol : 9/27/2012<br>carol : 2/23/2012<br>terry : 2/23/2012<br>wwang : 8/15/2007<br>terry : 7/10/2007<br>carol : 3/19/2007<br>alopez : 12/7/2006<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>wwang : 6/17/2005<br>wwang : 6/9/2005<br>terry : 6/8/2005<br>alopez : 6/15/2001<br>terry : 6/14/2001<br>dkim : 12/11/1998<br>carol : 12/11/1998<br>terry : 11/18/1998<br>alopez : 11/13/1998
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603286
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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KISS1 METASTASIS SUPPRESSOR; KISS1
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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METASTIN<br />
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KISSPEPTIN
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<div>
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<br />
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: KISS1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 1q32.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:204,190,341-204,196,491 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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1q32.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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?Hypogonadotropic hypogonadism 13 with or without anosmia
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</span>
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</td>
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<td>
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<span class="mim-font">
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614842
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>KISS1 was originally identified as a metastasis suppressor gene encoding an array of structurally related peptides, called kisspeptins, which act through the G protein-coupled receptor GPR54 (KISS1R; 604161). KISS1 has a role in the neuroendocrine control of gonadotropin secretion (summary by Navarro et al., 2005). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Welch et al. (1994) found that microcell-mediated transfer of human chromosome 6 into human metastatic melanoma cells (C8161 or MelJuSo) suppressed their ability to metastasize in athymic nude mice by at least 95% without affecting the tumorigenicity of the cells. </p><p>Using a modified subtractive hybridization approach, Lee et al. (1996) isolated a cDNA expressed in hybrid chromosome 6-C8161 cells but not in parental C8161 cells. They designated the cDNA KISS1, combining laboratory nomenclature for putative suppressor sequences with acknowledgment of the gene's discovery in Hershey, Pennsylvania. Lee et al. (1996) reported the sequence of the predicted KISS1 protein and a corrected sequence in a published erratum. The KISS1 protein consists of 145 amino acids. Northern blot analysis revealed that KISS1 was expressed as a 1-kb mRNA in chromosome 6-C8161 hybrid cell lines as well as in normal placenta tissue. Low levels of smaller transcripts were observed in pancreas and kidney. Lee et al. (1996) did not detect KISS1 expression in any cell line capable of metastasizing in athymic nude mice. </p><p>Ohtaki et al. (2001) demonstrated that KISS1 encodes a carboxy-terminally amidated peptide with 54 amino acid residues, which the authors isolated from human placenta as the endogenous ligand of an orphan G protein-coupled receptor (GPR54; 604161). They named the truncated form of KISS1 'metastin.' </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By fluorescence in situ hybridization (FISH), Lee et al. (1996) mapped the KISS1 gene to 1q32-q41. They suggested that a metastasis-suppressing gene or genes on chromosome 6 regulate KISS1. By radiation hybrid mapping and FISH, West et al. (1998) localized the KISS1 gene to 1q32. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Lee et al. (1996) observed that expression of KISS1 in C8161 melanoma cells suppressed metastasis, suggesting that KISS1 plays a role in the regulation of cancer metastasis in human malignant melanoma. Lee and Welch (1997) demonstrated that expression of KISS1 in human breast carcinoma cells reduced metastatic potential by 95% compared to control cells but did not suppress tumorigenicity. The authors concluded that KISS1 also functions as a metastasis suppressor gene in at least some human breast cancers. </p><p>Ohtaki et al. (2001) found that metastin inhibited chemotaxis and invasion of GPR54-transfected CHO cells in vitro and attenuated pulmonary metastasis of GPR54-transfected B16-BL6 melanomas in vivo. </p><p>Using real-time PCR, Shahab et al. (2005) found that expression of Kiss1 mRNA increased with puberty in both male and female rhesus monkeys. Kisspeptin-10 (112-121), a decapeptide derived from KISS1, was administered to agonadal juvenile monkeys and induced a GnRH (152760) response as measured by a surge in plasma luteinizing hormone (LH; see 152780). In intact females, but not in agonadal males, the level of Gpr54 mRNA in the hypothalamus increased about 3-fold from the juvenile to midpubertal stage. In situ hybridization detected robust Kiss1 and Gpr54 expression in the arcuate nucleus. Shahab et al. (2005) concluded that KISS1 signaling through GPR54 in the primate hypothalamus at the end of the juvenile phase of development may contribute to the pubertal resurgence of pulsatile GnRH release. </p><p>Kinoshita et al. (2005) examined whether metastin, the product of metastasis suppressor gene KISS1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Injection of metastin into the third ventricle or preoptic area increased plasma LH concentrations in estrogen-primed ovariectomized rats, demonstrating that metastin profoundly stimulates LH secretion by acting on the preoptic area, where most GnRH neurons projecting to the median eminence are located. Immunohistochemical analysis demonstrated metastin neurons in the arcuate nucleus colocalized with estrogen receptors, with some fibers in the preoptic area in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR revealed KISS1 and GPR54 (606161) mRNAs expressed in the arcuate nucleus and preoptic area, respectively. The blockade of local metastin action in the preoptic area with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. In the arcuate nucleus, numbers of metastin-immunoreactive cell bodies and c-Fos (164810) expression were significantly higher in the early proestrus afternoon compared with the day of diestrus. Thus, Kinoshita et al. (2005) concluded that metastin released in the preoptic area is involved in inducing the preovulatory LH surge and regulating estrous cyclicity. </p><p>Navarro et al. (2005) studied the effect of KISS1 peptide on LH secretion using in vitro and in vivo settings under different experimental conditions. Central intracerebroventricular administration of KISS1 peptide potently elicited LH secretion in vivo over a range of doses from 10 pmol to 1 nmol. The effect of centrally injected KISS1 appeared to be mediated via the hypothalamic LHRH. However, no effect of central administration of KISS1 was detected on relative LHRH mRNA levels. Likewise, systemic (either intraperitoneal or intravascular) injection of KISS1 markedly stimulated LH secretion. Navarro et al. (2005) found that LH-releasing activity of KISS1 was persistently observed after blockade of endogenous excitatory amino acid and nitric oxide pathways, i.e., relevant neurotransmitters in the neuroendocrine control of LH secretion. Navarro et al. (2005) concluded that their results provided solid evidence for a potent stimulatory effect of KISS1 on LH release, acting at central levels (likely the hypothalamus) and eventually at the pituitary, and further documented a novel role of the KISS1/GPR54 system as a relevant downstream element in the neuroendocrine network governing LH secretion. </p><p>Smith et al. (2005) found that KISS1 neurons in the arcuate nucleus, which are inhibited by estradiol, may play a role in the negative feedback regulation of GnRH secretion, whereas KISS1 neurons in the anteroventral periventricular nucleus, which are stimulated by estradiol, may participate in the positive feedback regulation of GnRH secretion. </p><p>Navarro et al. (2005) studied the effects of KISS1 peptide on FSH (see 136530) secretion in vivo and in vitro. Intracerebroventricular administration of KISS1 peptide significantly stimulated FSH secretion in prepubertal and adult rats. Yet, dose-response analyses in vivo demonstrated an ED50 value for the FSH-releasing effects of KISS1 of 400 pmol, i.e., approximately 100-fold higher than that of LH. In addition, systemic injection of KISS1 significantly stimulated FSH secretion in vivo. However, KISS1 failed to elicit basal FSH release directly at the pituitary level, although it moderately enhanced GnRH-stimulated FSH secretion in vitro. Finally, Navarro et al. (2005) reported that mechanistic studies revealed that the ability of KISS1 to elicit FSH secretion was abolished by the blockade of endogenous GnRH actions, but it was persistently observed in different models of leptin (164160) insufficiency and after blockade of endogenous excitatory amino acid and nitric oxide pathways, relevant signals in the neuroendocrine control of gonadotropin secretion. In summary, Navarro et al. (2005) concluded that their results extended previous observations on the role of KISS1 in the control of LH secretion and provided solid evidence for a stimulatory effect of KISS1 on FSH release, acting at a central level. </p><p>In a study of 6 healthy male volunteers, Dhillo et al. (2005) found that elevation of plasma concentrations of kisspeptin significantly increased circulating LH, FSH, and testosterone levels. Dhillo et al. (2005) suggested that kisspeptin infusion may provide a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p><strong><em>Hypogonadotropic Hypogonadism 13</em></strong></p><p>
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In a consanguineous Kurdish family in which 4 sisters had normosmic hypogonadotropic hypogonadism (HH13; 614842), Topaloglu et al. (2012) identified homozygosity for a missense mutation in the KISS1 gene (603286.0001) that segregated with the disease and was not found in 100 ethnically matched controls. Subsequent analysis of KISS1 in 12 additional families with normosmic hypogonadotropic hypogonadism and in 90 sporadic cases revealed no mutations. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of an association between central precocious puberty (see 176400) and variation in the KISS1 gene, see 603286.0002.</p><p>In a cohort of 65 patients with adrenal steroid hypersecretion syndromes, Berthon et al. (2020) analyzed the KISS1 and KISS1R genes and identified 1 patient with primary aldosteronism (see 103900) and hypercortisolism (see 610489) who was heterozygous for an H90D variant (rs201073751) in the KISS1 gene. The authors noted that the variant, present in the gnomAD database with a minor allele frequency (MAF) of 0.00137, was relatively frequent in the African population (MAF = 0.022 in Africans). </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>D'Anglemont de Tassigny et al. (2007) generated Kiss1-null mice that were viable and healthy with no apparent abnormalities but failed to undergo sexual maturation. Mutant female mice did not progress through the estrous cycle, had thread-like uteri and small ovaries, and did not produce mature Graffian follicles. Mutant males had small testes, and spermatogenesis arrested mainly at the early haploid spermatid stage. Both sexes had low circulating gonadotropin (LH and FSH) and sex steroid (beta-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appeared normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic-pituitary axis was functional, as shown by robust LH secretion after peripheral administration of kisspeptin. D'Anglemont de Tassigny et al. (2007) stated that the phenotypes of Gpr54- and Kiss1-null mice are virtually identical, providing direct proof that kisspeptins are the true physiologic ligand for the GPR54 receptor in vivo. The authors also noted that apart from activation of the hypothalamic-pituitary-gonadal axis, KISS1 does not seem to play a vital role in any other physiologic processes, and loss of KISS1 cannot be overcome by compensatory mechanisms. </p><p>In Kiss1 -/- female mice, Berthon et al. (2020) performed histologic analysis of the adrenal glands at 5 months and 12 months of age and observed persistence of the X-zone, a region formed by cells that retain fetal characteristics that normally degenerates after the first pregnancy in female mice and after puberty in males. There was increased expression of X-zone markers, suggesting that the X-zone was expanded in the mutant mice. The authors observed hypercorticosteronism in the female mutants that normalized by 12 months of age; hyperaldosteronism was present in both male and female mutants and persisted at 14 months. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>2 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 HYPOGONADOTROPIC HYPOGONADISM 13 WITHOUT ANOSMIA (1 family)</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KISS1, ASN115LYS
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<br />
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SNP: rs587777835,
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gnomAD: rs587777835,
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ClinVar: RCV000030951
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<div>
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<span class="mim-text-font">
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<p>In 4 affected sisters from a consanguineous Kurdish family with normosmic hypogonadotropic hypogonadism (HH13; 614842), Topaloglu et al. (2012) identified homozygosity for a 345C-G transversion in the KISS1 gene, resulting in an asn115-to-lys (N115K) substitution at a highly conserved residue. The unaffected parents were heterozygous for the mutation, and unaffected sibs were heterozygous or homozygous for wildtype. The mutation was not found in 100 ethnically matched controls. Functional studies showed that human KISS1R (604161) had significantly reduced sensitivity to mutant kisspeptin-10, and mutant kisspeptin-10 was unable to stimulate a maximal inositol phosphate response at any concentration tested, indicating significantly reduced efficacy as well as potency. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KISS1, PRO74SER
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<br />
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SNP: rs587777843,
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gnomAD: rs587777843,
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ClinVar: RCV000144560
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>This variant is classified as a variant of unknown significance because its contribution to central precocious puberty (see 176400) has not been confirmed.</p><p>In a 16-year-old Brazilian boy with central precocious puberty, Silveira et al. (2010) sequenced the 3 exons of the KISS1 gene and identified heterozygosity for a c.369C-T transition in exon 3, resulting in a pro74-to-ser (P74S) substitution at a highly conserved residue within a PEST sequence in the amino-terminal region. The mutation was also detected in heterozygosity in the patient's unaffected mother and maternal grandmother, who both had menarche at appropriate ages, but was not found in 400 control alleles. Functional analysis in CHO cells showed that the capacity of the mutant to stimulate inositol phosphate production was similar to that of wildtype; however, after incubation in human serum, the capacity to stimulate signal transduction was significantly greater with the mutant than with wildtype KISS1, suggesting that the P74S variant is more stable. The proband underwent pubertal development at 1 year of age, with enlargement of the penis and testes, Tanner stage III pubic hair, bone age of 3 years, and elevated levels of follicle-stimulating hormone, luteinizing hormone, and testosterone. He had no neurologic symptoms, and brain MRI was normal. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Berthon, A., Settas, N., Delaney, A., Giannakou, A., Demidowich, A., Faucz, F. R., Seminara, S. B., Chen, M. E., Stratakis, C. A.
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<strong>Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.</strong>
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Hum. Molec. Genet. 29: 3443-3450, 2020.
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[PubMed: 33089319]
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[Full Text: https://doi.org/10.1093/hmg/ddaa215]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P. C., Day, K., Leitch, H. G., Hendrick, A. G., Zahn, D., Franceschini, I., Caraty, A., Carlton, M. B. L., Aparicio, S. A. J. R., Colledge, W. H.
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<strong>Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene.</strong>
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Proc. Nat. Acad. Sci. 104: 10714-10719, 2007.
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[PubMed: 17563351]
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[Full Text: https://doi.org/10.1073/pnas.0704114104]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., Bloom, S. R.
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<strong>Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males.</strong>
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J. Clin. Endocr. Metab. 90: 6609-6615, 2005.
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[PubMed: 16174713]
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[Full Text: https://doi.org/10.1210/jc.2005-1468]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., Maeda, K.-I.
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<strong>Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats.</strong>
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Endocrinology 146: 4431-4436, 2005.
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[PubMed: 15976058]
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[Full Text: https://doi.org/10.1210/en.2005-0195]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., Welch, D. R.
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<strong>KiSS-1, a novel human malignant melanoma metastasis-suppressor gene.</strong>
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J. Nat. Cancer Inst. 88: 1731-1737, 1996. Note: Erratum: J. Nat. Cancer Inst. 89: 1549 only, 1997.
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[PubMed: 8944003]
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[Full Text: https://doi.org/10.1093/jnci/88.23.1731]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lee, J.-H., Welch, D. R.
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<strong>Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1.</strong>
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Cancer Res. 57: 2384-2387, 1997.
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[PubMed: 9192814]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Roa, J., Mayen, A., Nogueiras, R., Vazquez, M. J., Barreiro, M. L., Magni, P., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
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<strong>Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.</strong>
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Endocrinology 146: 156-163, 2005.
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[PubMed: 15375028]
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[Full Text: https://doi.org/10.1210/en.2004-0836]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Navarro, V. M., Castellano, J. M., Fernandez-Fernandez, R., Tovar, S., Road, J., Mayen, A., Barreiro, M. L., Casanueva, F. F., Aguilar, E., Dieguez, C., Pinilla, L., Tena-Sempere, M.
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<strong>Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.</strong>
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Endocrinology 146: 1689-1697, 2005.
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[PubMed: 15637288]
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[Full Text: https://doi.org/10.1210/en.2004-1353]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., Ishibashi, Y., Watanabe, T., and 9 others.
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<strong>Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.</strong>
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Nature 411: 613-617, 2001.
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[PubMed: 11385580]
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[Full Text: https://doi.org/10.1038/35079135]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shahab, M., Mastronardi, C., Seminara, S. B., Crowley, W. F., Ojeda, S. R., Plant, T. M.
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<strong>Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.</strong>
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Proc. Nat. Acad. Sci. 102: 2129-2134, 2005.
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[PubMed: 15684075]
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[Full Text: https://doi.org/10.1073/pnas.0409822102]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Silveira, L. G., Noel, S. D., Silveira-Neto, A. P., Abreu, A. P., Brito, V. N., Santos, M. G., Bianco, S. D. C., Kuohung, W., Xu, S., Gryngarten, M., Escobar, M. E., Arnhold, I. J. P., Mendonca, B. B., Kaiser, U. B., Latronico, A. C.
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<strong>Mutations of the KISS1 gene in disorders of puberty.</strong>
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J. Clin. Endocr. Metab. 95: 2276-2280, 2010.
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[PubMed: 20237166]
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[Full Text: https://doi.org/10.1210/jc.2009-2421]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., Steiner, R. A.
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<strong>Regulation of Kiss1 gene expression in the brain of the female mouse.</strong>
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Endocrinology 146: 3686-3692, 2005.
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[PubMed: 15919741]
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[Full Text: https://doi.org/10.1210/en.2005-0488]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Topaloglu, A. K., Tello, J. A., Kotan, L. D., Ozbek, M. N., Yilmaz, M. B., Erdogan, S., Gurbuz, F., Temiz, F., Millar, R. P., Yuksel, B.
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<strong>Inactivating KISS1 mutation and hypogonadotropic hypogonadism.</strong>
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New Eng. J. Med. 366: 629-635, 2012.
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[PubMed: 22335740]
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[Full Text: https://doi.org/10.1056/NEJMoa1111184]
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Welch, D. R., Chen, P., Miele, M. E., McGary, C. T., Bower, J. M., Stanbridge, E. J., Weissman, B. E.
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<strong>Microcell-mediated transfer of chromosome 6 into metastatic human C8161 melanoma cells suppresses metastasis but does not inhibit tumorigenicity.</strong>
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Oncogene 9: 255-262, 1994.
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[PubMed: 8302587]
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West, A., Vojta, P. J., Welch, D. R., Weissman, B. E.
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<strong>Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1).</strong>
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Genomics 54: 145-148, 1998.
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[PubMed: 9806840]
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[Full Text: https://doi.org/10.1006/geno.1998.5566]
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Marla J. F. O'Neill - updated : 02/17/2022<br>Marla J. F. O'Neill - updated : 10/10/2014<br>Marla J. F. O'Neill - updated : 2/23/2012<br>Marla J. F. O'Neill - updated : 7/10/2007<br>John A. Phillips, III - updated : 3/19/2007<br>Ada Hamosh - updated : 11/28/2006<br>Patricia A. Hartz - updated : 6/8/2005<br>Ada Hamosh - updated : 6/14/2001<br>Carol A. Bocchini - updated : 12/11/1998
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Rebekah S. Rasooly : 11/13/1998
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alopez : 02/21/2025<br>alopez : 02/17/2022<br>carol : 10/15/2014<br>mcolton : 10/14/2014<br>mcolton : 10/10/2014<br>carol : 10/3/2012<br>carol : 9/27/2012<br>carol : 2/23/2012<br>terry : 2/23/2012<br>wwang : 8/15/2007<br>terry : 7/10/2007<br>carol : 3/19/2007<br>alopez : 12/7/2006<br>alopez : 12/7/2006<br>terry : 11/28/2006<br>wwang : 6/17/2005<br>wwang : 6/9/2005<br>terry : 6/8/2005<br>alopez : 6/15/2001<br>terry : 6/14/2001<br>dkim : 12/11/1998<br>carol : 12/11/1998<br>terry : 11/18/1998<br>alopez : 11/13/1998
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