3376 lines
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Entry
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- *603930 - GEPHYRIN; GPHN
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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">*603930</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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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="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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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="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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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/603930">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 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>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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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=ENSG00000171723;t=ENST00000478722" 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=10243" 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=603930" 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=ENSG00000171723;t=ENST00000478722" 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_001024218,NM_001377514,NM_001377515,NM_001377516,NM_001377517,NM_001377518,NM_001377519,NM_020806,XM_011536340,XM_011536342,XM_011536343,XM_011536344,XM_011536345,XM_017020913,XM_017020914,XM_017020917,XM_017020918,XM_047430875,XM_047430876,XM_047430877,XM_047430878,XM_047430879,XM_047430880" 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_020806" 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=603930" 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=04893&isoform_id=04893_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/GPHN" 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/8926308,10636475,10880983,13431554,16605466,20988629,66932975,119601329,119601330,119601331,119601332,189054960,221040076,221040818,221041812,767979516,767979518,767979520,767979522,767979524,929654515,1034585946,1034585949,1034585959,1034585961,1798088742,1798088753,1798088769,1798088780,1798088806,1798088812,2217296105,2217296108,2217296113,2217296115,2217296117,2217296119,2462538576,2462538578,2462538580,2462538582,2462538584,2462538586,2462538588,2462538590,2462538592,2462538594,2462538596,2462538598,2462538600,2462538602,2462538604,2462538606" 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/Q9NQX3" 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=10243" 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=ENSG00000171723;t=ENST00000478722" 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=GPHN" 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=GPHN" 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+10243" 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/GPHN" 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:10243" 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/10243" 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=chr14&hgg_gene=ENST00000478722.6&hgg_start=66508147&hgg_end=67735355&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:15465" 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://search.clinicalgenome.org/kb/genes/HGNC:15465" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/gphn" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603930[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=603930[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/ENSG00000171723" 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=GPHN" 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=GPHN" 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=GPHN" 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=GPHN&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/PA28840" 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:15465" 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://flybase.org/reports/FBgn0000316.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:109602" 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/GPHN#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:109602" 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/10243/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://www.orthodb.org/?ncbi=10243" 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://wormbase.org/db/gene/gene?name=WBGene00003384;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-070705-4" 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">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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:10243" 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=GPHN&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>
|
|
<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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|
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<a id="title" class="mim-anchor"></a>
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<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
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|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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|
<strong>SNOMEDCT:</strong> 1003387003<br />
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">ICD+</a>
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</div>
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
603930
|
|
</span>
|
|
</span>
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</div>
|
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</div>
|
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<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
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|
|
GEPHYRIN; GPHN
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</span>
|
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</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
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|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
GPH; GEPH<br />
|
|
KIAA1385
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
MLL/GPHN FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GPHN" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GPHN</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/321?start=-3&limit=10&highlight=321">14q23.3-q24.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:66508147-67735355&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'})">14:66,508,147-67,735,355</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/321?start=-3&limit=10&highlight=321">
|
|
14q23.3-q24.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Molybdenum cofactor deficiency C
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615501"> 615501 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
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</span>
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<p>The GPHN gene encodes gephyrin, an organizational protein that clusters and localizes the inhibitory glycine and GABA receptors to the microtubular matrix of the neuronal postsynaptic membrane (summary by <a href="#12" class="mim-tip-reference" title="Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C.-H., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., Snell, R. G. <strong>Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia.</strong> J. Biol. Chem. 278: 24688-24696, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12684523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12684523</a>] [<a href="https://doi.org/10.1074/jbc.M301070200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12684523">Rees et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12684523" 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>To integrate signals from the many synaptic connections on its cell body and dendrites rapidly and specifically, a neuron anchors high concentrations of receptors at postsynaptic sites, matching the correct receptor with the neurotransmitter released from the presynaptic terminal. Receptor-associated proteins are thought to be involved in forming these postsynaptic specializations, possibly by linking the receptor to the postsynaptic cytoskeleton (<a href="#8" class="mim-tip-reference" title="Kirsch, J., Wolters, I., Triller, A., Betz, H. <strong>Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons.</strong> Nature 366: 745-748, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8264797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8264797</a>] [<a href="https://doi.org/10.1038/366745a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8264797">Kirsch et al., 1993</a>). Gephyrin is essential for both the postsynaptic localization of inhibitory neurotransmitter receptors in the central nervous system and the biosynthesis of the molybdenum cofactor (MoCo) in different peripheral organs (<a href="#16" class="mim-tip-reference" title="Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, J., Mendel, R. R. <strong>The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.</strong> Proc. Nat. Acad. Sci. 96: 1333-1338, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9990024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9990024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9990024[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.96.4.1333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9990024">Stallmeyer et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9990024+8264797" 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="#10" class="mim-tip-reference" title="Prior, P., Schmitt, B., Grenningloh, G., Pribilla, I., Multhaup, G., Beyreuther, K., Maulet, Y., Werner, P., Langosch, D., Kirsch, J., Betz, H. <strong>Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.</strong> Neuron 8: 1161-1170, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1319186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1319186</a>] [<a href="https://doi.org/10.1016/0896-6273(92)90136-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1319186">Prior et al. (1992)</a> cloned the rat gene encoding a 93-kD protein that is associated with the mammalian inhibitory glycine receptor (see <a href="/entry/138492">138492</a>). They designated this protein 'gephyrin,' from the Greek word meaning 'bridge,' because it binds with high affinity to polymerized tubulin, suggesting that it may serve as a receptor-microtubule linker. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1319186" 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><a href="#11" class="mim-tip-reference" title="Ramming, M., Kins, S., Werner, N., Hermann, A., Betz, H., Kirsch, J. <strong>Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins.</strong> Proc. Nat. Acad. Sci. 97: 10266-10271, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10963686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10963686</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10963686[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.97.18.10266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10963686">Ramming et al. (2000)</a> described gephyrin splice variants that were differentially expressed in nonneural tissues and different regions of the adult mouse brain. They found that the mouse gephyrin gene shows a highly mosaic organization, with 8 of its 29 exons corresponding to an alternatively spliced region identified by cDNA sequencing. The N- and C-terminal domains of gephyrin, encoded by exons 3-7 and 16-29, respectively, displayed sequence similarities to bacterial, invertebrate, and plant proteins involved in Moco biosynthesis, whereas the central exons 8, 13, and 14 encode motifs that may mediate oligomerization and tubulin binding. The data were consistent with the evolution of gephyrin from a Moco biosynthetic protein by insertion of protein interaction sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10963686" 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>By searching databases for sequences homologous to rat Geph, <a href="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> identified a brain tissue cDNA containing the complete coding sequence of human GPHN. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11095995" 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><a href="#12" class="mim-tip-reference" title="Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C.-H., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., Snell, R. G. <strong>Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia.</strong> J. Biol. Chem. 278: 24688-24696, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12684523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12684523</a>] [<a href="https://doi.org/10.1074/jbc.M301070200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12684523">Rees et al. (2003)</a> isolated gephyrin cDNAs and by RT-PCR analysis of human tissues demonstrated the presence of 5 alternatively spliced GPHN exons concentrated in the central linker region of the gene. This region generated 11 distinct GPHN transcript isoforms, with 10 being specific to neuronal tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12684523" 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="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> determined that the GPHN gene contains 22 exons spanning approximately 375 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11095995" 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>By genomic sequence analysis, <a href="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> mapped the GPHN gene to chromosome 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11095995" 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="Kirsch, J., Wolters, I., Triller, A., Betz, H. <strong>Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons.</strong> Nature 366: 745-748, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8264797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8264797</a>] [<a href="https://doi.org/10.1038/366745a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8264797">Kirsch et al. (1993)</a> demonstrated that gephyrin is essential for localizing the inhibitory glycine receptor to presumptive postsynaptic plasma membrane specializations. <a href="#4" class="mim-tip-reference" title="Essrich, C., Lorez, M., Benson, J. A., Fritschy, J.-M., Luscher, B. <strong>Postsynaptic clustering of major GABA(A) receptor subtypes requires the gamma-2 subunit and gephyrin.</strong> Nature Neurosci. 1: 563-571, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10196563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10196563</a>] [<a href="https://doi.org/10.1038/2798" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10196563">Essrich et al. (1998)</a> found that gephyrin is also required for clustering and postsynaptic localization of GABA(A) receptors. <a href="#15" class="mim-tip-reference" title="Sabatini, D. M., Barrow, R. K., Blackshaw, S., Burnett, P. E., Lai, M. M., Field, M. E., Bahr, B. A., Kirsch, J., Betz, H., Snyder, S. H. <strong>Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling.</strong> Science 284: 1161-1164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10325225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10325225</a>] [<a href="https://doi.org/10.1126/science.284.5417.1161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10325225">Sabatini et al. (1999)</a> determined that gephyrin interacts with RAFT1 (FRAP; <a href="/entry/601231">601231</a>) in mammalian cells. RAFT1 is an ATM (<a href="/entry/607585">607585</a>)-related protein that appears to participate in mitogen-stimulated signaling pathways that control mRNA translation. RAFT1 mutants that could not associate with gephyrin failed to signal to downstream molecules. <a href="#15" class="mim-tip-reference" title="Sabatini, D. M., Barrow, R. K., Blackshaw, S., Burnett, P. E., Lai, M. M., Field, M. E., Bahr, B. A., Kirsch, J., Betz, H., Snyder, S. H. <strong>Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling.</strong> Science 284: 1161-1164, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10325225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10325225</a>] [<a href="https://doi.org/10.1126/science.284.5417.1161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10325225">Sabatini et al. (1999)</a> concluded that gephyrin plays a role in signal transduction. They reported that all tissues examined, including a human embryonic kidney cell line, contained RAFT1 and gephyrin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10196563+10325225+8264797" 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><a href="#10" class="mim-tip-reference" title="Prior, P., Schmitt, B., Grenningloh, G., Pribilla, I., Multhaup, G., Beyreuther, K., Maulet, Y., Werner, P., Langosch, D., Kirsch, J., Betz, H. <strong>Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.</strong> Neuron 8: 1161-1170, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1319186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1319186</a>] [<a href="https://doi.org/10.1016/0896-6273(92)90136-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1319186">Prior et al. (1992)</a> noted that the C-terminal region of rat gephyrin shares 36% amino acid identity with the E. coli ChlE (MoeA) protein, which is thought to be involved in bacterial molybdopterin biosynthesis. <a href="#16" class="mim-tip-reference" title="Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, J., Mendel, R. R. <strong>The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.</strong> Proc. Nat. Acad. Sci. 96: 1333-1338, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9990024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9990024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9990024[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.96.4.1333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9990024">Stallmeyer et al. (1999)</a> stated that the N-terminal region of gephyrin is homologous to MogA, a second E. coli molybdenum cofactor (MoCo) biosynthesis protein. They demonstrated that gephyrin binds with high affinity to molybdopterin, the metabolic precursor of Moco. Gephyrin expression reconstituted Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. <a href="#16" class="mim-tip-reference" title="Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, J., Mendel, R. R. <strong>The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.</strong> Proc. Nat. Acad. Sci. 96: 1333-1338, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9990024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9990024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9990024[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.96.4.1333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9990024">Stallmeyer et al. (1999)</a> concluded that gephyrin plays a role in Moco biosynthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1319186+9990024" 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><a href="#1" class="mim-tip-reference" title="Butler, M. H., Hayashi, A., Ohkoshi, N., Villmann, C., Becker, C.-M., Feng, G., De Camilli, P., Solimena, M. <strong>Autoimmunity to gephyrin in stiff-man syndrome.</strong> Neuron 26: 307-312, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839351</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)81165-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10839351">Butler et al. (2000)</a> identified high-titer autoantibodies directed against GPH in a patient with mediastinal cancer and clinical features of stiff-man syndrome (<a href="/entry/184850">184850</a>). Their findings provided evidence for a link between autoimmunity directed against components of inhibitory synapses and neurologic conditions characterized by chronic rigidity and spasms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10839351" 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><strong><em>The MLL/GPHN Fusion Gene</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Eguchi, M., Eguchi-Ishimae, M., Seto, M., Morishita, K., Suzuki, K., Ueda, R., Ueda, K., Kamada, N., Greaves, M. <strong>GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).</strong> Genes Chromosomes Cancer 32: 212-221, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11579461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11579461</a>] [<a href="https://doi.org/10.1002/gcc.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11579461">Eguchi et al. (2001)</a> found that the gephyrin gene can partner with MLL (<a href="/entry/159555">159555</a>) in leukemia associated with the translocation t(11;14)(q23;q24). The child in whom this translocation was discovered showed signs of acute undifferentiated leukemia 3 years after intensive chemotherapy that included the topoisomerase II inhibitor VP16. The AT hook motifs and a DNA methyltransferase homology domain of the MLL gene were fused to the C-terminal half of the gephyrin gene, including the presumed tubulin-binding site and a domain homologous to the E. coli molybdenum cofactor biosynthesis protein. <a href="#3" class="mim-tip-reference" title="Eguchi, M., Eguchi-Ishimae, M., Seto, M., Morishita, K., Suzuki, K., Ueda, R., Ueda, K., Kamada, N., Greaves, M. <strong>GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).</strong> Genes Chromosomes Cancer 32: 212-221, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11579461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11579461</a>] [<a href="https://doi.org/10.1002/gcc.1185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11579461">Eguchi et al. (2001)</a> suggested that MLL-GPHN may have been generated by the chemotherapeutic agent, followed by error-prone DNA repair via nonhomologous end-joining. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11579461" 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>The MLL (mixed lineage leukemia) gene forms chimeric fusions with a diverse set of partner genes as a consequence of chromosome translocations in leukemia. In several fusion partners, a transcriptional activation domain appears to be essential for conferring leukemogenic capacity on MLL protein. Other fusion partners, however, lack such domains. <a href="#2" class="mim-tip-reference" title="Eguchi, M., Eguchi-Ishimae, M., Greaves, M. <strong>The small oligomerization domain of gephyrin converts MLL to an oncogene.</strong> Blood 103: 3876-3882, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14751928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14751928</a>] [<a href="https://doi.org/10.1182/blood-2003-11-3817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14751928">Eguchi et al. (2004)</a> showed that gephyrin, a neuronal receptor assembly protein and rare fusion partner of MLL in leukemia, has the capacity as an MLL-GPHN chimera to transform hematopoietic progenitors, despite lack of transcriptional activity. They found that a small 15-amino acid tubulin-binding domain of GPHN is necessary and sufficient for this activity in vitro and in vivo. This domain also confers oligomerization capacity on MLL protein, suggesting that such activity may contribute critically to leukemogenesis. The transduction of MLL-GPHN into hematopoietic progenitor cells caused myeloid and lymphoid lineage leukemias in mice, suggesting that MLL-GPHN can target multipotent progenitor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14751928" 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>The sequence of gephyrin shares homology with the proteins necessary for the biosynthesis of MoCo: MoCo synthesis-1 (MOCS1; <a href="/entry/603707">603707</a>) and MoCo synthesis-2 (MOCS2; <a href="/entry/603708">603708</a>). Because gephyrin expression can rescue a MoCo-deficient mutation in bacteria, plants, and a murine cell line, it is clear that gephyrin also plays a role in MoCo biosynthesis. Human molybdenum cofactor deficiency is a fatal disease resulting in severe neurologic damage and death in early childhood. Most patients harbor MOCS1 mutations, which prohibit the formation of a precursor, or carry MOCS2 mutations, which abrogate precursor conversion to molybdopterin. In a patient with symptoms typical of molybdenum cofactor deficiency type C (MOCODC; <a href="/entry/615501">615501</a>), <a href="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> identified a homozygous deletion in the GEPH gene (<a href="#0001">603930.0001</a>). Biochemical studies of the patient's fibroblasts demonstrated that gephyrin catalyzes the insertion of molybdenum into molybdopterin and suggested that this novel form of molybdenum cofactor deficiency might be curable by molybdate supplementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11095995" 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 an Algerian girl with MOCODC, <a href="#14" class="mim-tip-reference" title="Reiss, J., Lenz, U., Aquaviva-Bourdain, C., Joriot-Chekaf, S., Mention-Mulliez, K., Holder-Espinasse, M. <strong>A GPHN point mutation leading to molybdenum cofactor deficiency. (Letter)</strong> Clin. Genet. 80: 598-599, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22040219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22040219</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2011.01709.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22040219">Reiss et al. (2011)</a> identified a homozygous mutation in the GPHN gene (D580A; <a href="#0002">603930.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22040219" 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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---Hyperekplexia</p><p>For discussion of a possible role of variation in the GPHN gene in hyperekplexia (see <a href="/entry/149400">149400</a>), see <a href="#0002">603930.0002</a>.</p><p>---Neuropsychiatric Disorders</p><p><a href="#9" class="mim-tip-reference" title="Lionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., Merico, D., Prasad, A., and 20 others. <strong>Rare exonic deletions implicate the synaptic organizer gephyrin (GPHN) in risk for autism, schizophrenia and seizures.</strong> Hum. Molec. Genet. 22: 2055-2066, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23393157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23393157</a>] [<a href="https://doi.org/10.1093/hmg/ddt056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23393157">Lionel et al. (2013)</a> presented evidence that heterozygous deletions of exons 3 to 5 of the GPHN gene may play a role in the risk for neurodevelopmental disorders, particularly autism spectrum disorders (ASD; see <a href="/entry/209850">209850</a>) and schizophrenia (SCZD; see <a href="/entry/181500">181500</a>). The GPHN gene was selected for study because of its functional links with several synaptic proteins that have been implicated in neurodevelopmental disorders, including NLGN4 (<a href="/entry/300427">300427</a>) and NRXN2 (<a href="/entry/600566">600566</a>), as well as its role in receptor stability at the synapse. Copy number variant analysis identified heterozygous deletions at chromosome 14q23.3 interrupting multiple exons of the GPHN gene in 5 of 5,384 individuals from cohorts of patients with ASD, schizophrenia, and seizure disorders. A sixth patient with schizophrenia and a heterozygous deletion affecting the GPHN gene was also included in the study; this patient had previously been reported (<a href="#7" class="mim-tip-reference" title="International Schizophrenia Consortium. <strong>Rare chromosomal deletions and duplications increase risk of schizophrenia.</strong> Nature 455: 237-241, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18668038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18668038</a>] [<a href="https://doi.org/10.1038/nature07239" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18668038">International Schizophrenia Consortium, 2008</a>). The deletions ranged in size from 183 to 357 kb; 1 breakpoint was shared by 3 patients. No exonic deletions at the GPHN locus were reported in the Database of Genomic Variants, and CNVs at this locus were only found in 3 of 27,019 controls. The frequency of deletions was significantly greater in patients (6 of 8,775) compared to controls (3 of 27,019, p = 0.009). Three of the deletions were proven to occur de novo in patients with ASD, ASD with seizures, and schizophrenia, respectively. Parental information was not available from the fourth patient, who had seizures. A deletion found in a fifth patient, who had ASD, was inherited from a father with subclinical social skills; there was significant psychiatric history on both sides of the family. The sixth patient, who had schizophrenia, inherited the deletion from an unaffected mother whose mother reportedly had schizophrenia. The common region of overlap encompassed exons 3 to 5 of the GPHN gene, corresponding to the coding segment of the G domain, which is vital to the formation of gephyrin scaffolds. <a href="#9" class="mim-tip-reference" title="Lionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., Merico, D., Prasad, A., and 20 others. <strong>Rare exonic deletions implicate the synaptic organizer gephyrin (GPHN) in risk for autism, schizophrenia and seizures.</strong> Hum. Molec. Genet. 22: 2055-2066, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23393157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23393157</a>] [<a href="https://doi.org/10.1093/hmg/ddt056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23393157">Lionel et al. (2013)</a> pointed to the study of <a href="#6" class="mim-tip-reference" title="Forstera, B., Belaidi, A. A., Juttner, R., Bernert, C., Tsokos, M., Lehmann, T.-N., Horn, P., Dehnicke, C., Schwarz, G., Meier, J. C. <strong>Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of patients with epilepsy.</strong> Brain 133: 3778-3794, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21071388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21071388</a>] [<a href="https://doi.org/10.1093/brain/awq298" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21071388">Forstera et al. (2010)</a>, who found expression of abnormally spliced GPHN mRNA in the hippocampus of patients with temporal lobe epilepsy (see <a href="/entry/600512">600512</a>) in the absence of GPHN mutations. The splice variants lacked several exons corresponding to the G domain, and the aberrant protein variants were unable to form trimers. The abnormal variants acted in a dominant-negative manner, resulting in a depletion of GABA receptor cluster density and reduced GABAergic postsynaptic current amplitudes. <a href="#6" class="mim-tip-reference" title="Forstera, B., Belaidi, A. A., Juttner, R., Bernert, C., Tsokos, M., Lehmann, T.-N., Horn, P., Dehnicke, C., Schwarz, G., Meier, J. C. <strong>Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of patients with epilepsy.</strong> Brain 133: 3778-3794, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21071388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21071388</a>] [<a href="https://doi.org/10.1093/brain/awq298" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21071388">Forstera et al. (2010)</a> concluded that expression of these variant GPHN isoforms may reduce seizure threshold by reducing inhibitory currents under certain physiologic conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21071388+18668038+23393157" 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="Feng, G., Tintrup, H., Kirsch, J., Nichol, M. C., Kuhse, J., Betz, H., Sanes, J. R. <strong>Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.</strong> Science 282: 1321-1324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9812897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9812897</a>] [<a href="https://doi.org/10.1126/science.282.5392.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9812897">Feng et al. (1998)</a> used gene targeting to disrupt the mouse gephyrin gene. Homozygous gephyrin-null mutant mice were born without apparent developmental abnormalities but died within 1 day. Neonatal mutant animals responded in an exaggerated way to a light touch on the skin, becoming rigid and hyperextended and having difficulty breathing. Using the mutant animals, the authors demonstrated that gephyrin is required both for synaptic clustering of glycine receptors in spinal cord and for molybdoenzyme activity in nonneural tissues. To determine whether the neurologic symptoms were due to disruption of glycinergic synapses or to a molybdenum cofactor deficiency, <a href="#5" class="mim-tip-reference" title="Feng, G., Tintrup, H., Kirsch, J., Nichol, M. C., Kuhse, J., Betz, H., Sanes, J. R. <strong>Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.</strong> Science 282: 1321-1324, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9812897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9812897</a>] [<a href="https://doi.org/10.1126/science.282.5392.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9812897">Feng et al. (1998)</a> injected neonatal mice with strychnine, a specific antagonist of the inhibitory glycine receptor. The injection phenocopied the motor symptoms of gephyrin deficiency, consistent with the idea that the phenotype is primarily attributable to the failure of glycinergic synaptic activity. The mutant phenotype resembled that of human patients with hereditary molybdenum cofactor deficiency (see <a href="/entry/615501">615501</a>) and hyperekplexia (see <a href="/entry/149400">149400</a>), leading the authors to suggest that gephyrin function may be impaired in both diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9812897" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603930[MIM]" class="btn btn-default mim-tip-hint" role="button" 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>
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<strong>.0001 MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C</strong>
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GPHN, EX2-3DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006336" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006336" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006336</a>
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<p><a href="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> studied the last of 3 affected infants born to a Danish mother and father who were cousins. All 3 died in the neonatal period (at day 12, 29, and 3, respectively), with symptoms identical to those of molybdenum cofactor (MoCo) deficiency (MOCODC; <a href="/entry/615501">615501</a>). Three other pregnancies of the mother resulted in 2 healthy sibs and 1 spontaneous abortion. The first affected infant was a boy; the other 2 were girls. All showed hypotonia combined with hyperreflexia, as well as tonic-clonic convulsions. Fibroblasts of the third infant were used to verify molybdenum cofactor deficiency by biochemical and in vitro complementation assays and to isolate DNA for genetic analysis. <a href="#13" class="mim-tip-reference" title="Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G. <strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong> Am. J. Hum. Genet. 68: 208-213, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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/10.1086/316941" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11095995">Reiss et al. (2001)</a> identified a deletion of exons 2 and 3 of the GPHN gene, resulting in a frameshift after only 21 codons of normal coding sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11095995" 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="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908539 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908539;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/rs121908539?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=rs121908539" 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=rs121908539" 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=RCV000006337 OR RCV000031964 OR RCV000697829 OR RCV002496282 OR RCV002512829 OR RCV003480022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006337, RCV000031964, RCV000697829, RCV002496282, RCV002512829, RCV003480022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006337...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to hyperekplexia has not been confirmed.</p><p>In 1 of 38 unrelated patients with hyperekplexia (see <a href="/entry/149400">149400</a>), <a href="#12" class="mim-tip-reference" title="Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C.-H., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., Snell, R. G. <strong>Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia.</strong> J. Biol. Chem. 278: 24688-24696, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12684523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12684523</a>] [<a href="https://doi.org/10.1074/jbc.M301070200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12684523">Rees et al. (2003)</a> detected a heterozygous 28A-T transversion in exon 1 of the GPHN gene, resulting in an asn10-to-tyr (N10Y) substitution at the extreme N terminus. The N10Y variant was not found in 94 controls. The GPHN gene was chosen for sequencing after it was shown to interact with the GLRB (<a href="/entry/138492">138492</a>) subunit. The N10Y substitution is located 5 residues upstream from a putative region important for protein interactions; however, in vitro functional expression studies in HEK293 cells suggested that the variant did not affect the structural lattices formed by gephyrin or interrupt its interactions with GLRB. The variant protein did not interrupt cell surface clustering. Thus, the functional effect of the variant remained elusive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12684523" 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>.0003 MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397518420 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397518420;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397518420" 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=rs397518420" 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=RCV000074361" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000074361" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000074361</a>
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<p>In a girl, born of consanguineous Algerian parents, with molybdenum cofactor deficiency of complementation group C (MOCODC; <a href="/entry/615501">615501</a>), <a href="#14" class="mim-tip-reference" title="Reiss, J., Lenz, U., Aquaviva-Bourdain, C., Joriot-Chekaf, S., Mention-Mulliez, K., Holder-Espinasse, M. <strong>A GPHN point mutation leading to molybdenum cofactor deficiency. (Letter)</strong> Clin. Genet. 80: 598-599, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22040219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22040219</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2011.01709.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22040219">Reiss et al. (2011)</a> identified a homozygous c.1739A-C transversion in exon 18 of the GPHN gene, resulting in an asp580-to-ala (D580A) substitution at a highly conserved residue in the E domain. The unaffected parents were heterozygous for the mutation. The E domain is believed to hydrolyze adenylylated molybdopterin while inserting the molybdenum to yield active cofactor. Accordingly, sulfite oxidase activity in patient fibroblasts could not be detected even after incubation with molybdate. The patient presented as a neonate with poor feeding, hypotonia, and intractable seizures. At age 2 years, she had spasticity and lack of psychomotor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22040219" 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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Butler, M. H., Hayashi, A., Ohkoshi, N., Villmann, C., Becker, C.-M., Feng, G., De Camilli, P., Solimena, M.
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<strong>Autoimmunity to gephyrin in stiff-man syndrome.</strong>
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Neuron 26: 307-312, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10839351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10839351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10839351" 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/10.1016/s0896-6273(00)81165-4" target="_blank">Full Text</a>]
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<strong>The small oligomerization domain of gephyrin converts MLL to an oncogene.</strong>
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Blood 103: 3876-3882, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14751928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14751928</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14751928" 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/10.1182/blood-2003-11-3817" target="_blank">Full Text</a>]
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Eguchi, M., Eguchi-Ishimae, M., Seto, M., Morishita, K., Suzuki, K., Ueda, R., Ueda, K., Kamada, N., Greaves, M.
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<strong>GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).</strong>
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Genes Chromosomes Cancer 32: 212-221, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11579461/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11579461</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11579461" 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/10.1002/gcc.1185" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/2798" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.282.5392.1321" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/brain/awq298" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature07239" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/366745a0" target="_blank">Full Text</a>]
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Lionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., Merico, D., Prasad, A., and 20 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23393157/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23393157</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23393157" 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/ddt056" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1319186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1319186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1319186" 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/10.1016/0896-6273(92)90136-2" target="_blank">Full Text</a>]
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<strong>Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10963686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10963686</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10963686[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=10963686" 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.97.18.10266" target="_blank">Full Text</a>]
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Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C.-H., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., Snell, R. G.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12684523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12684523</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12684523" 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/10.1074/jbc.M301070200" target="_blank">Full Text</a>]
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Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G.
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<strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11095995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11095995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11095995[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=11095995" 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/10.1086/316941" target="_blank">Full Text</a>]
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Reiss, J., Lenz, U., Aquaviva-Bourdain, C., Joriot-Chekaf, S., Mention-Mulliez, K., Holder-Espinasse, M.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22040219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22040219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22040219" 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/10.1111/j.1399-0004.2011.01709.x" target="_blank">Full Text</a>]
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Sabatini, D. M., Barrow, R. K., Blackshaw, S., Burnett, P. E., Lai, M. M., Field, M. E., Bahr, B. A., Kirsch, J., Betz, H., Snyder, S. H.
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<strong>Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling.</strong>
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Science 284: 1161-1164, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10325225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10325225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10325225" 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/10.1126/science.284.5417.1161" target="_blank">Full Text</a>]
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Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, J., Mendel, R. R.
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<strong>The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9990024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9990024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9990024[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=9990024" 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.96.4.1333" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 10/30/2013
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Cassandra L. Kniffin - updated : 5/8/2012<br>Victor A. McKusick - updated : 8/9/2006<br>Victor A. McKusick - updated : 6/30/2006<br>Victor A. McKusick - updated : 10/6/2004<br>Victor A. McKusick - updated : 7/11/2003<br>Carol A. Bocchini - reorganized : 7/8/2002<br>Victor A. McKusick - updated : 12/13/2001<br>Dawn Watkins-Chow - updated : 10/22/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 10/11/2000
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Rebekah S. Rasooly : 6/22/1999
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carol : 11/06/2013<br>carol : 11/5/2013<br>carol : 11/4/2013<br>ckniffin : 10/30/2013<br>carol : 6/5/2012<br>carol : 5/9/2012<br>carol : 5/9/2012<br>carol : 5/9/2012<br>ckniffin : 5/8/2012<br>carol : 8/11/2006<br>terry : 8/9/2006<br>alopez : 6/30/2006<br>terry : 6/30/2006<br>alopez : 10/8/2004<br>terry : 10/6/2004<br>cwells : 7/15/2003<br>terry : 7/11/2003<br>ckniffin : 3/11/2003<br>carol : 7/8/2002<br>mcapotos : 12/18/2001<br>terry : 12/13/2001<br>carol : 10/23/2001<br>carol : 10/22/2001<br>mgross : 1/24/2001<br>mgross : 1/24/2001<br>terry : 1/23/2001<br>joanna : 10/17/2000<br>carol : 10/13/2000<br>terry : 10/11/2000<br>alopez : 12/14/1999<br>alopez : 6/23/1999<br>alopez : 6/23/1999<br>alopez : 6/22/1999
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603930
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</span>
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<h3>
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<span class="mim-font">
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GEPHYRIN; GPHN
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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GPH; GEPH<br />
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KIAA1385
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</span>
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</h4>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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<span class="h3 mim-font">
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MLL/GPHN FUSION GENE, INCLUDED
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GPHN</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1003387003;
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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: 14q23.3-q24.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:66,508,147-67,735,355 </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 class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<td rowspan="1">
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<span class="mim-font">
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14q23.3-q24.1
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<td>
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<span class="mim-font">
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Molybdenum cofactor deficiency C
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<span class="mim-font">
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615501
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<td>
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<span class="mim-font">
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Autosomal recessive
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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 class="mim-font">
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<strong>TEXT</strong>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>The GPHN gene encodes gephyrin, an organizational protein that clusters and localizes the inhibitory glycine and GABA receptors to the microtubular matrix of the neuronal postsynaptic membrane (summary by Rees et al., 2003). </p><p>To integrate signals from the many synaptic connections on its cell body and dendrites rapidly and specifically, a neuron anchors high concentrations of receptors at postsynaptic sites, matching the correct receptor with the neurotransmitter released from the presynaptic terminal. Receptor-associated proteins are thought to be involved in forming these postsynaptic specializations, possibly by linking the receptor to the postsynaptic cytoskeleton (Kirsch et al., 1993). Gephyrin is essential for both the postsynaptic localization of inhibitory neurotransmitter receptors in the central nervous system and the biosynthesis of the molybdenum cofactor (MoCo) in different peripheral organs (Stallmeyer et al., 1999). </p>
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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 class="mim-text-font">
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<p>Prior et al. (1992) cloned the rat gene encoding a 93-kD protein that is associated with the mammalian inhibitory glycine receptor (see 138492). They designated this protein 'gephyrin,' from the Greek word meaning 'bridge,' because it binds with high affinity to polymerized tubulin, suggesting that it may serve as a receptor-microtubule linker. </p><p>Ramming et al. (2000) described gephyrin splice variants that were differentially expressed in nonneural tissues and different regions of the adult mouse brain. They found that the mouse gephyrin gene shows a highly mosaic organization, with 8 of its 29 exons corresponding to an alternatively spliced region identified by cDNA sequencing. The N- and C-terminal domains of gephyrin, encoded by exons 3-7 and 16-29, respectively, displayed sequence similarities to bacterial, invertebrate, and plant proteins involved in Moco biosynthesis, whereas the central exons 8, 13, and 14 encode motifs that may mediate oligomerization and tubulin binding. The data were consistent with the evolution of gephyrin from a Moco biosynthetic protein by insertion of protein interaction sequences. </p><p>By searching databases for sequences homologous to rat Geph, Reiss et al. (2001) identified a brain tissue cDNA containing the complete coding sequence of human GPHN. </p><p>Rees et al. (2003) isolated gephyrin cDNAs and by RT-PCR analysis of human tissues demonstrated the presence of 5 alternatively spliced GPHN exons concentrated in the central linker region of the gene. This region generated 11 distinct GPHN transcript isoforms, with 10 being specific to neuronal tissue. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</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>Reiss et al. (2001) determined that the GPHN gene contains 22 exons spanning approximately 375 kb. </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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<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 genomic sequence analysis, Reiss et al. (2001) mapped the GPHN gene to chromosome 14. </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>Gene Function</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>Kirsch et al. (1993) demonstrated that gephyrin is essential for localizing the inhibitory glycine receptor to presumptive postsynaptic plasma membrane specializations. Essrich et al. (1998) found that gephyrin is also required for clustering and postsynaptic localization of GABA(A) receptors. Sabatini et al. (1999) determined that gephyrin interacts with RAFT1 (FRAP; 601231) in mammalian cells. RAFT1 is an ATM (607585)-related protein that appears to participate in mitogen-stimulated signaling pathways that control mRNA translation. RAFT1 mutants that could not associate with gephyrin failed to signal to downstream molecules. Sabatini et al. (1999) concluded that gephyrin plays a role in signal transduction. They reported that all tissues examined, including a human embryonic kidney cell line, contained RAFT1 and gephyrin. </p><p>Prior et al. (1992) noted that the C-terminal region of rat gephyrin shares 36% amino acid identity with the E. coli ChlE (MoeA) protein, which is thought to be involved in bacterial molybdopterin biosynthesis. Stallmeyer et al. (1999) stated that the N-terminal region of gephyrin is homologous to MogA, a second E. coli molybdenum cofactor (MoCo) biosynthesis protein. They demonstrated that gephyrin binds with high affinity to molybdopterin, the metabolic precursor of Moco. Gephyrin expression reconstituted Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. Stallmeyer et al. (1999) concluded that gephyrin plays a role in Moco biosynthesis. </p><p>Butler et al. (2000) identified high-titer autoantibodies directed against GPH in a patient with mediastinal cancer and clinical features of stiff-man syndrome (184850). Their findings provided evidence for a link between autoimmunity directed against components of inhibitory synapses and neurologic conditions characterized by chronic rigidity and spasms. </p>
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</span>
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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>Cytogenetics</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><strong><em>The MLL/GPHN Fusion Gene</em></strong></p><p>
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Eguchi et al. (2001) found that the gephyrin gene can partner with MLL (159555) in leukemia associated with the translocation t(11;14)(q23;q24). The child in whom this translocation was discovered showed signs of acute undifferentiated leukemia 3 years after intensive chemotherapy that included the topoisomerase II inhibitor VP16. The AT hook motifs and a DNA methyltransferase homology domain of the MLL gene were fused to the C-terminal half of the gephyrin gene, including the presumed tubulin-binding site and a domain homologous to the E. coli molybdenum cofactor biosynthesis protein. Eguchi et al. (2001) suggested that MLL-GPHN may have been generated by the chemotherapeutic agent, followed by error-prone DNA repair via nonhomologous end-joining. </p><p>The MLL (mixed lineage leukemia) gene forms chimeric fusions with a diverse set of partner genes as a consequence of chromosome translocations in leukemia. In several fusion partners, a transcriptional activation domain appears to be essential for conferring leukemogenic capacity on MLL protein. Other fusion partners, however, lack such domains. Eguchi et al. (2004) showed that gephyrin, a neuronal receptor assembly protein and rare fusion partner of MLL in leukemia, has the capacity as an MLL-GPHN chimera to transform hematopoietic progenitors, despite lack of transcriptional activity. They found that a small 15-amino acid tubulin-binding domain of GPHN is necessary and sufficient for this activity in vitro and in vivo. This domain also confers oligomerization capacity on MLL protein, suggesting that such activity may contribute critically to leukemogenesis. The transduction of MLL-GPHN into hematopoietic progenitor cells caused myeloid and lymphoid lineage leukemias in mice, suggesting that MLL-GPHN can target multipotent progenitor cells. </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>Molecular Genetics</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>The sequence of gephyrin shares homology with the proteins necessary for the biosynthesis of MoCo: MoCo synthesis-1 (MOCS1; 603707) and MoCo synthesis-2 (MOCS2; 603708). Because gephyrin expression can rescue a MoCo-deficient mutation in bacteria, plants, and a murine cell line, it is clear that gephyrin also plays a role in MoCo biosynthesis. Human molybdenum cofactor deficiency is a fatal disease resulting in severe neurologic damage and death in early childhood. Most patients harbor MOCS1 mutations, which prohibit the formation of a precursor, or carry MOCS2 mutations, which abrogate precursor conversion to molybdopterin. In a patient with symptoms typical of molybdenum cofactor deficiency type C (MOCODC; 615501), Reiss et al. (2001) identified a homozygous deletion in the GEPH gene (603930.0001). Biochemical studies of the patient's fibroblasts demonstrated that gephyrin catalyzes the insertion of molybdenum into molybdopterin and suggested that this novel form of molybdenum cofactor deficiency might be curable by molybdate supplementation. </p><p>In an Algerian girl with MOCODC, Reiss et al. (2011) identified a homozygous mutation in the GPHN gene (D580A; 603930.0002). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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---Hyperekplexia</p><p>For discussion of a possible role of variation in the GPHN gene in hyperekplexia (see 149400), see 603930.0002.</p><p>---Neuropsychiatric Disorders</p><p>Lionel et al. (2013) presented evidence that heterozygous deletions of exons 3 to 5 of the GPHN gene may play a role in the risk for neurodevelopmental disorders, particularly autism spectrum disorders (ASD; see 209850) and schizophrenia (SCZD; see 181500). The GPHN gene was selected for study because of its functional links with several synaptic proteins that have been implicated in neurodevelopmental disorders, including NLGN4 (300427) and NRXN2 (600566), as well as its role in receptor stability at the synapse. Copy number variant analysis identified heterozygous deletions at chromosome 14q23.3 interrupting multiple exons of the GPHN gene in 5 of 5,384 individuals from cohorts of patients with ASD, schizophrenia, and seizure disorders. A sixth patient with schizophrenia and a heterozygous deletion affecting the GPHN gene was also included in the study; this patient had previously been reported (International Schizophrenia Consortium, 2008). The deletions ranged in size from 183 to 357 kb; 1 breakpoint was shared by 3 patients. No exonic deletions at the GPHN locus were reported in the Database of Genomic Variants, and CNVs at this locus were only found in 3 of 27,019 controls. The frequency of deletions was significantly greater in patients (6 of 8,775) compared to controls (3 of 27,019, p = 0.009). Three of the deletions were proven to occur de novo in patients with ASD, ASD with seizures, and schizophrenia, respectively. Parental information was not available from the fourth patient, who had seizures. A deletion found in a fifth patient, who had ASD, was inherited from a father with subclinical social skills; there was significant psychiatric history on both sides of the family. The sixth patient, who had schizophrenia, inherited the deletion from an unaffected mother whose mother reportedly had schizophrenia. The common region of overlap encompassed exons 3 to 5 of the GPHN gene, corresponding to the coding segment of the G domain, which is vital to the formation of gephyrin scaffolds. Lionel et al. (2013) pointed to the study of Forstera et al. (2010), who found expression of abnormally spliced GPHN mRNA in the hippocampus of patients with temporal lobe epilepsy (see 600512) in the absence of GPHN mutations. The splice variants lacked several exons corresponding to the G domain, and the aberrant protein variants were unable to form trimers. The abnormal variants acted in a dominant-negative manner, resulting in a depletion of GABA receptor cluster density and reduced GABAergic postsynaptic current amplitudes. Forstera et al. (2010) concluded that expression of these variant GPHN isoforms may reduce seizure threshold by reducing inhibitory currents under certain physiologic conditions. </p>
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<div>
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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 class="mim-text-font">
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<p>Feng et al. (1998) used gene targeting to disrupt the mouse gephyrin gene. Homozygous gephyrin-null mutant mice were born without apparent developmental abnormalities but died within 1 day. Neonatal mutant animals responded in an exaggerated way to a light touch on the skin, becoming rigid and hyperextended and having difficulty breathing. Using the mutant animals, the authors demonstrated that gephyrin is required both for synaptic clustering of glycine receptors in spinal cord and for molybdoenzyme activity in nonneural tissues. To determine whether the neurologic symptoms were due to disruption of glycinergic synapses or to a molybdenum cofactor deficiency, Feng et al. (1998) injected neonatal mice with strychnine, a specific antagonist of the inhibitory glycine receptor. The injection phenocopied the motor symptoms of gephyrin deficiency, consistent with the idea that the phenotype is primarily attributable to the failure of glycinergic synaptic activity. The mutant phenotype resembled that of human patients with hereditary molybdenum cofactor deficiency (see 615501) and hyperekplexia (see 149400), leading the authors to suggest that gephyrin function may be impaired in both diseases. </p>
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</span>
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<div>
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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>3 Selected Examples):</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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<h4>
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<span class="mim-font">
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<strong>.0001 MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C</strong>
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</span>
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<span class="mim-text-font">
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GPHN, EX2-3DEL
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<br />
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ClinVar: RCV000006336
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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>Reiss et al. (2001) studied the last of 3 affected infants born to a Danish mother and father who were cousins. All 3 died in the neonatal period (at day 12, 29, and 3, respectively), with symptoms identical to those of molybdenum cofactor (MoCo) deficiency (MOCODC; 615501). Three other pregnancies of the mother resulted in 2 healthy sibs and 1 spontaneous abortion. The first affected infant was a boy; the other 2 were girls. All showed hypotonia combined with hyperreflexia, as well as tonic-clonic convulsions. Fibroblasts of the third infant were used to verify molybdenum cofactor deficiency by biochemical and in vitro complementation assays and to isolate DNA for genetic analysis. Reiss et al. (2001) identified a deletion of exons 2 and 3 of the GPHN gene, resulting in a frameshift after only 21 codons of normal coding sequence. </p>
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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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GPHN, ASN10TYR
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<br />
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SNP: rs121908539,
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gnomAD: rs121908539,
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ClinVar: RCV000006337, RCV000031964, RCV000697829, RCV002496282, RCV002512829, RCV003480022
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<p>This variant is classified as a variant of unknown significance because its contribution to hyperekplexia has not been confirmed.</p><p>In 1 of 38 unrelated patients with hyperekplexia (see 149400), Rees et al. (2003) detected a heterozygous 28A-T transversion in exon 1 of the GPHN gene, resulting in an asn10-to-tyr (N10Y) substitution at the extreme N terminus. The N10Y variant was not found in 94 controls. The GPHN gene was chosen for sequencing after it was shown to interact with the GLRB (138492) subunit. The N10Y substitution is located 5 residues upstream from a putative region important for protein interactions; however, in vitro functional expression studies in HEK293 cells suggested that the variant did not affect the structural lattices formed by gephyrin or interrupt its interactions with GLRB. The variant protein did not interrupt cell surface clustering. Thus, the functional effect of the variant remained elusive. </p>
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<h4>
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<span class="mim-font">
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<strong>.0003 MOLYBDENUM COFACTOR DEFICIENCY, COMPLEMENTATION GROUP C</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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GPHN, ASP580ALA
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SNP: rs397518420,
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ClinVar: RCV000074361
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<p>In a girl, born of consanguineous Algerian parents, with molybdenum cofactor deficiency of complementation group C (MOCODC; 615501), Reiss et al. (2011) identified a homozygous c.1739A-C transversion in exon 18 of the GPHN gene, resulting in an asp580-to-ala (D580A) substitution at a highly conserved residue in the E domain. The unaffected parents were heterozygous for the mutation. The E domain is believed to hydrolyze adenylylated molybdopterin while inserting the molybdenum to yield active cofactor. Accordingly, sulfite oxidase activity in patient fibroblasts could not be detected even after incubation with molybdate. The patient presented as a neonate with poor feeding, hypotonia, and intractable seizures. At age 2 years, she had spasticity and lack of psychomotor development. </p>
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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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<ol>
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<p class="mim-text-font">
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Butler, M. H., Hayashi, A., Ohkoshi, N., Villmann, C., Becker, C.-M., Feng, G., De Camilli, P., Solimena, M.
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<strong>Autoimmunity to gephyrin in stiff-man syndrome.</strong>
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Neuron 26: 307-312, 2000.
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[PubMed: 10839351]
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[Full Text: https://doi.org/10.1016/s0896-6273(00)81165-4]
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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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Eguchi, M., Eguchi-Ishimae, M., Greaves, M.
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<strong>The small oligomerization domain of gephyrin converts MLL to an oncogene.</strong>
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Blood 103: 3876-3882, 2004.
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[PubMed: 14751928]
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[Full Text: https://doi.org/10.1182/blood-2003-11-3817]
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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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Eguchi, M., Eguchi-Ishimae, M., Seto, M., Morishita, K., Suzuki, K., Ueda, R., Ueda, K., Kamada, N., Greaves, M.
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<strong>GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).</strong>
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Genes Chromosomes Cancer 32: 212-221, 2001.
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[PubMed: 11579461]
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[Full Text: https://doi.org/10.1002/gcc.1185]
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</li>
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<li>
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<p class="mim-text-font">
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Essrich, C., Lorez, M., Benson, J. A., Fritschy, J.-M., Luscher, B.
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<strong>Postsynaptic clustering of major GABA(A) receptor subtypes requires the gamma-2 subunit and gephyrin.</strong>
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Nature Neurosci. 1: 563-571, 1998.
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[PubMed: 10196563]
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[Full Text: https://doi.org/10.1038/2798]
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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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Feng, G., Tintrup, H., Kirsch, J., Nichol, M. C., Kuhse, J., Betz, H., Sanes, J. R.
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<strong>Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.</strong>
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Science 282: 1321-1324, 1998.
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[PubMed: 9812897]
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[Full Text: https://doi.org/10.1126/science.282.5392.1321]
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</li>
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<li>
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<p class="mim-text-font">
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Forstera, B., Belaidi, A. A., Juttner, R., Bernert, C., Tsokos, M., Lehmann, T.-N., Horn, P., Dehnicke, C., Schwarz, G., Meier, J. C.
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<strong>Irregular RNA splicing curtails postsynaptic gephyrin in the cornu ammonis of patients with epilepsy.</strong>
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Brain 133: 3778-3794, 2010.
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[PubMed: 21071388]
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[Full Text: https://doi.org/10.1093/brain/awq298]
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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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International Schizophrenia Consortium.
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<strong>Rare chromosomal deletions and duplications increase risk of schizophrenia.</strong>
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Nature 455: 237-241, 2008.
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[PubMed: 18668038]
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[Full Text: https://doi.org/10.1038/nature07239]
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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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Kirsch, J., Wolters, I., Triller, A., Betz, H.
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<strong>Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons.</strong>
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Nature 366: 745-748, 1993.
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[PubMed: 8264797]
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[Full Text: https://doi.org/10.1038/366745a0]
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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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Lionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., Merico, D., Prasad, A., and 20 others.
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<strong>Rare exonic deletions implicate the synaptic organizer gephyrin (GPHN) in risk for autism, schizophrenia and seizures.</strong>
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Hum. Molec. Genet. 22: 2055-2066, 2013.
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[PubMed: 23393157]
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[Full Text: https://doi.org/10.1093/hmg/ddt056]
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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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Prior, P., Schmitt, B., Grenningloh, G., Pribilla, I., Multhaup, G., Beyreuther, K., Maulet, Y., Werner, P., Langosch, D., Kirsch, J., Betz, H.
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<strong>Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.</strong>
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Neuron 8: 1161-1170, 1992.
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[PubMed: 1319186]
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[Full Text: https://doi.org/10.1016/0896-6273(92)90136-2]
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<li>
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<p class="mim-text-font">
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Ramming, M., Kins, S., Werner, N., Hermann, A., Betz, H., Kirsch, J.
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<strong>Diversity and phylogeny of gephyrin: tissue-specific splice variants, gene structure, and sequence similarities to molybdenum cofactor-synthesizing and cytoskeleton-associated proteins.</strong>
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Proc. Nat. Acad. Sci. 97: 10266-10271, 2000.
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[PubMed: 10963686]
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[Full Text: https://doi.org/10.1073/pnas.97.18.10266]
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Rees, M. I., Harvey, K., Ward, H., White, J. H., Evans, L., Duguid, I. C., Hsu, C. C.-H., Coleman, S. L., Miller, J., Baer, K., Waldvogel, H. J., Gibbon, F., Smart, T. G., Owen, M. J., Harvey, R. J., Snell, R. G.
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<strong>Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia.</strong>
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J. Biol. Chem. 278: 24688-24696, 2003.
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[PubMed: 12684523]
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[Full Text: https://doi.org/10.1074/jbc.M301070200]
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<p class="mim-text-font">
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Reiss, J., Gross-Hardt, S., Christensen, E., Schmidt, P., Mendel, R. R., Schwarz, G.
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<strong>A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.</strong>
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Am. J. Hum. Genet. 68: 208-213, 2001.
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[PubMed: 11095995]
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[Full Text: https://doi.org/10.1086/316941]
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<li>
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<p class="mim-text-font">
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Reiss, J., Lenz, U., Aquaviva-Bourdain, C., Joriot-Chekaf, S., Mention-Mulliez, K., Holder-Espinasse, M.
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<strong>A GPHN point mutation leading to molybdenum cofactor deficiency. (Letter)</strong>
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Clin. Genet. 80: 598-599, 2011.
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[PubMed: 22040219]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2011.01709.x]
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Sabatini, D. M., Barrow, R. K., Blackshaw, S., Burnett, P. E., Lai, M. M., Field, M. E., Bahr, B. A., Kirsch, J., Betz, H., Snyder, S. H.
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<strong>Interaction of RAFT1 with gephyrin required for rapamycin-sensitive signaling.</strong>
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Science 284: 1161-1164, 1999.
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[PubMed: 10325225]
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[Full Text: https://doi.org/10.1126/science.284.5417.1161]
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Stallmeyer, B., Schwarz, G., Schulze, J., Nerlich, A., Reiss, J., Kirsch, J., Mendel, R. R.
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<strong>The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.</strong>
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Proc. Nat. Acad. Sci. 96: 1333-1338, 1999.
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[PubMed: 9990024]
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[Full Text: https://doi.org/10.1073/pnas.96.4.1333]
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Contributors:
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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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Cassandra L. Kniffin - updated : 10/30/2013<br>Cassandra L. Kniffin - updated : 5/8/2012<br>Victor A. McKusick - updated : 8/9/2006<br>Victor A. McKusick - updated : 6/30/2006<br>Victor A. McKusick - updated : 10/6/2004<br>Victor A. McKusick - updated : 7/11/2003<br>Carol A. Bocchini - reorganized : 7/8/2002<br>Victor A. McKusick - updated : 12/13/2001<br>Dawn Watkins-Chow - updated : 10/22/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 10/11/2000
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Creation Date:
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<span class="mim-text-font">
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Rebekah S. Rasooly : 6/22/1999
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carol : 05/06/2024<br>carol : 11/06/2013<br>carol : 11/5/2013<br>carol : 11/4/2013<br>ckniffin : 10/30/2013<br>carol : 6/5/2012<br>carol : 5/9/2012<br>carol : 5/9/2012<br>carol : 5/9/2012<br>ckniffin : 5/8/2012<br>carol : 8/11/2006<br>terry : 8/9/2006<br>alopez : 6/30/2006<br>terry : 6/30/2006<br>alopez : 10/8/2004<br>terry : 10/6/2004<br>cwells : 7/15/2003<br>terry : 7/11/2003<br>ckniffin : 3/11/2003<br>carol : 7/8/2002<br>mcapotos : 12/18/2001<br>terry : 12/13/2001<br>carol : 10/23/2001<br>carol : 10/22/2001<br>mgross : 1/24/2001<br>mgross : 1/24/2001<br>terry : 1/23/2001<br>joanna : 10/17/2000<br>carol : 10/13/2000<br>terry : 10/11/2000<br>alopez : 12/14/1999<br>alopez : 6/23/1999<br>alopez : 6/23/1999<br>alopez : 6/22/1999
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To ensure long-term funding for the OMIM project, we have diversified
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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