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<title>
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Entry
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- *610863 - GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-4; GNB4
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- OMIM
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<p />
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*610863</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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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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>
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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="#geneStructure">Gene Structure</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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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="#molecularGenetics">Molecular Genetics</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/610863">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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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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</nav>
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</div>
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</div>
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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=ENSG00000114450;t=ENST00000232564" 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=59345" 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=610863" 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=ENSG00000114450;t=ENST00000232564" 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_021629,XM_005247692,XM_006713721,XM_047448653,XM_047448654" 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_021629" 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=610863" 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=09973&isoform_id=09973_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/GNB4" 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/10505346,11055998,12654119,22256759,40032497,119598809,119598810,158254574,193786011,194386206,530375105,578807646,2104758971,2217345314,2217345316,2462591682,2462591684,2462591686,2462591688" 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/Q9HAV0" 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=59345" 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=ENSG00000114450;t=ENST00000232564" 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=GNB4" 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=GNB4" 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+59345" 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/GNB4" 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:59345" 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/59345" 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=chr3&hgg_gene=ENST00000232564.8&hgg_start=179396088&hgg_end=179527798&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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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/genes/HGNC:20731" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=610863[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=610863[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/ENSG00000114450" 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=GNB4" 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=GNB4" 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=GNB4" 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=GNB4&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/PA134864200" 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:20731" 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/FBgn0001105.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:104581" 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/GNB4#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:104581" 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/59345/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=59345" 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=WBGene00001679;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-041114-167" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
|
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<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:59345" 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=GNB4&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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<a id="title" class="mim-anchor"></a>
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<div>
|
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<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> 770759001<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>
|
|
610863
|
|
</span>
|
|
</span>
|
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</div>
|
|
</div>
|
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<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
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|
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GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-4; GNB4
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
G PROTEIN, BETA-4 SUBUNIT; G BETA-4
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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</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=GNB4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNB4</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/3/880?start=-3&limit=10&highlight=880">3q26.33</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:179396088-179527798&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'})">3:179,396,088-179,527,798</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
</span>
|
|
</p>
|
|
</div>
|
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<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
|
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</th>
|
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<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/3/880?start=-3&limit=10&highlight=880">
|
|
3q26.33
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<p>Heterotrimeric G proteins, made up of an alpha subunit (see GNAS, <a href="/entry/139320">139320</a>), a beta subunit, like GNB4, and a gamma subunit (see GNG2, <a href="/entry/606981">606981</a>), relay signals from cell surface receptors to internal effectors. The alpha subunit is a GTPase that interacts in the GDP-bound state with beta-gamma dimers (<a href="#4" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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 searching an EST database for G-protein beta-like sequences, followed by 5-prime RACE of a human brain cDNA library, <a href="#5" class="mim-tip-reference" title="Ruiz-Velasco, V., Ikeda, S. R., Puhl, H. L. <strong>Cloning, tissue distribution, and functional expression of the human G protein beta-4-subunit.</strong> Physiol. Genomics 8: 41-50, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11842130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11842130</a>] [<a href="https://doi.org/10.1152/physiolgenomics.00085.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11842130">Ruiz-Velasco et al. (2002)</a> cloned GNB4. Like other beta subunits, the deduced GNB4 protein contains 340 amino acids with 7 WD repeat motifs forming a beta-propeller structure. GNB4 shares 91% identity with GNB1 (<a href="/entry/139380">139380</a>) and 96% identity with mouse Gnb4. PCR analysis detected high GNB4 expression in human lung, pancreas, and placenta, moderate expression in kidney and liver, and weak expression in brain and heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11842130" 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 an EST database for sequences similar to mouse Gnb4, followed by PCR of human B lymphoblast and brain RNA, <a href="#4" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> cloned GNB4. PCR analysis of human, rat, and mouse tissues and cultured cells showed wide GNB4 expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> found that GNB4 colocalized with neurofilament heavy chain and S100 in peripheral human nerves, indicating that it is expressed in both axons and Schwann cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23434117" 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 heterologous overexpression in rat sympathetic neurons, <a href="#5" class="mim-tip-reference" title="Ruiz-Velasco, V., Ikeda, S. R., Puhl, H. L. <strong>Cloning, tissue distribution, and functional expression of the human G protein beta-4-subunit.</strong> Physiol. Genomics 8: 41-50, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11842130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11842130</a>] [<a href="https://doi.org/10.1152/physiolgenomics.00085.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11842130">Ruiz-Velasco et al. (2002)</a> found that human G-beta-4 coexpressed with G-gamma-2 (GNG2; <a href="/entry/606981">606981</a>) or G-gamma-4 (GNG4; <a href="/entry/604388">604388</a>) caused tonic modulation of N-type voltage-gated calcium currents and G protein-gated inwardly rectifying potassium currents. Coexpression of G-beta-4, G-gamma-2 and G-alpha-oA (GNAO1; <a href="/entry/139311">139311</a>) resulted in heterotrimer formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11842130" 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>Using coprecipitation analysis, <a href="#4" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> showed that GNB4 formed dimers with all 11 gamma subunits analyzed. The strength of the interaction was variable and was strongest between GNB1 and GNG4, followed by GNG13 (<a href="/entry/607298">607298</a>) and GNG1 (GNGT1; <a href="/entry/189970">189970</a>), and was weakest with GNG8C (GNGT2; <a href="/entry/139391">139391</a>). Overexpression of most GNB4-GNG dimers resulted in significant, although sometimes modest, activation of phospholipase beta-2 (PLCB2; <a href="/entry/604114">604114</a>), with highest activation by the GNB4-GNG4 dimer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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>Vertebrate retinas have distinct light-on (ON) and light-off (OFF) channels that originate at the level of the retinal bipolar cells. For the conversion from OFF to ON, ON bipolar cells use the GNAO1-coupled glutamate receptor-6 (GRIK2; <a href="/entry/138244">138244</a>) such that binding of glutamate suppresses a cation current rather than activating it. Using immunohistochemical analysis and single-cell PCR, <a href="#2" class="mim-tip-reference" title="Huang, L., Max, M., Margolskee, R. F., Su, H., Masland, R. H., Euler, T. <strong>G protein subunit G-gamma-13 is coexpressed with G-alpha-o, G-beta-3, and G-beta-4 in retinal ON bipolar cells.</strong> J. Comp. Neurol. 455: 1-10, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12454992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12454992</a>] [<a href="https://doi.org/10.1002/cne.10396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12454992">Huang et al. (2003)</a> showed that the gamma subunit Gng13 (<a href="/entry/607298">607298</a>) was coexpressed with the beta subunits Gnb3 (<a href="/entry/139130">139130</a>) and Gnb4, but no other beta subunit, in dissociated mouse ON bipolar cells. <a href="#2" class="mim-tip-reference" title="Huang, L., Max, M., Margolskee, R. F., Su, H., Masland, R. H., Euler, T. <strong>G protein subunit G-gamma-13 is coexpressed with G-alpha-o, G-beta-3, and G-beta-4 in retinal ON bipolar cells.</strong> J. Comp. Neurol. 455: 1-10, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12454992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12454992</a>] [<a href="https://doi.org/10.1002/cne.10396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12454992">Huang et al. (2003)</a> hypothesized that these G protein subunits selectively participate in signal transduction in ON bipolar cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12454992" 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="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> found that Gnb4 expression in rats decreased in nerve tissue distal to sciatic nerve transection and increased in nerve tissue after conditioning, suggesting that the protein plays a role in peripheral nerve regeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23434117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> determined that the GNB4 gene contains 10 exons. The first exon is noncoding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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="#4" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> mapped the GNB4 gene to chromosome 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 3/9/2018."None>Gross (2018)</a> mapped the GNB4 gene to chromosome 3q26.33 based on an alignment of the GNB4 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF300648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF300648</a>) with the genomic sequence (GRCh38).</p>
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<p>In affected members of a Han Chinese family with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; <a href="/entry/615185">615185</a>) (<a href="#3" class="mim-tip-reference" title="Lee, Y.-C., Lee, T.-C., Lin, K.-P, Lin, M.-W., Chang, M.-H, Soong, B.-W. <strong>Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease.</strong> Neuromusc. Disord. 20: 534-539, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20627571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20627571</a>] [<a href="https://doi.org/10.1016/j.nmd.2010.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20627571">Lee et al., 2010</a>), <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> identified a heterozygous mutation in the GNB4 gene (G53D; <a href="#0001">610863.0001</a>). The mutation was identified by exome sequencing. An unrelated Han Chinese girl with demyelinating CMT carried a different heterozygous mutation that occurred de novo (K89E; <a href="#0002">610863.0002</a>). The frequency of GNB4 mutations in the CMT cohort was 0.8% (2 of 251 families). The phenotype was characterized by onset around adolescence of slowly progressive distal muscle weakness and atrophy affecting the upper and lower limbs, as well as distal sensory impairment and areflexia. In the family, male mutation carriers were more severely affected than female mutation carriers. Immunofluorescence studies of patient sural nerves showed GNB4 staining of onion bulb formations in a rosette pattern. However, immunohistochemical studies showed weaker GNB4 expression in patient sural nerve biopsies compared to controls. Expression of both mutations in COS-7 cells showed that the mutant proteins had impaired bradykinin-induced G protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant proteins were stable in transfected cells, and <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> postulated a dominant-negative effect. The findings indicated that GNB4-related G protein-coupled receptor signaling is important for proper functioning of peripheral nerves. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23434117+20627571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a large 4-generation Han Chinese family with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; <a href="/entry/615185">615185</a>), <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> identified a heterozygous 158G-A transition in the GNB4 gene, resulting in a gly53-to-asp (G53D) substitution at a highly conserved residue. The mutation, which was identified by exome sequencing, segregated with the disorder in the family and was not found in several large control databases, including 1,920 ethnic control chromosomes. The phenotype was characterized by onset around adolescence of slowly progressive distal muscle weakness and atrophy affecting the upper and lower limbs, as well as distal sensory impairment. Male mutation carriers were more severely affected than female mutation carriers. Expression of the mutation in COS-7 cells showed that the mutant protein had impaired bradykinin-induced G-protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant protein was stable in transfected cells, and <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> postulated a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23434117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 9-year-old Han Chinese girl with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; <a href="/entry/615185">615185</a>), <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> identified a de novo heterozygous 265A-G transition in exon 5 of the GNB4 gene, resulting in a lys89-to-glu (K89E) substitution at a highly conserved residue. The mutation was not found in several large control databases, including 1,920 ethnic control chromosomes. Expression of the mutation in COS-7 cells showed that the mutant protein had impaired bradykinin-induced G-protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant protein was stable in transfected cells, and <a href="#6" class="mim-tip-reference" title="Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C. <strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong> Am. J. Hum. Genet. 92: 422-430, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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/10.1016/j.ajhg.2013.01.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23434117">Soong et al. (2013)</a> postulated a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23434117" 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>G protein subunit G-gamma-13 is coexpressed with G-alpha-o, G-beta-3, and G-beta-4 in retinal ON bipolar cells.</strong>
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J. Comp. Neurol. 455: 1-10, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12454992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12454992</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12454992" 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/cne.10396" target="_blank">Full Text</a>]
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<strong>Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease.</strong>
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Neuromusc. Disord. 20: 534-539, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20627571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20627571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20627571" 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/j.nmd.2010.05.001" target="_blank">Full Text</a>]
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Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W.
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<strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong>
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FEBS Lett. 544: 27-32, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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/s0014-5793(03)00441-1" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Ruiz-Velasco2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ruiz-Velasco, V., Ikeda, S. R., Puhl, H. L.
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<strong>Cloning, tissue distribution, and functional expression of the human G protein beta-4-subunit.</strong>
|
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Physiol. Genomics 8: 41-50, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11842130/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11842130</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11842130" 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/10.1152/physiolgenomics.00085.2001" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Soong2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C.
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<strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong>
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Am. J. Hum. Genet. 92: 422-430, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23434117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23434117</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23434117[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=23434117" 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/j.ajhg.2013.01.014" target="_blank">Full Text</a>]
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</ol>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 03/09/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 4/18/2013
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</span>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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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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Patricia A. Hartz : 3/20/2007
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</div>
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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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mgross : 03/09/2018
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/07/2018<br>carol : 04/22/2013<br>carol : 4/19/2013<br>ckniffin : 4/18/2013<br>terry : 1/4/2011<br>wwang : 3/20/2007
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 610863
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-4; GNB4
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</h3>
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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G PROTEIN, BETA-4 SUBUNIT; G BETA-4
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</span>
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</h4>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GNB4</em></strong>
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</span>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 770759001;
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</span>
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<strong>
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<em>
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Cytogenetic location: 3q26.33
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:179,396,088-179,527,798 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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3q26.33
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<td>
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<span class="mim-font">
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Charcot-Marie-Tooth disease, dominant intermediate F
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</span>
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</td>
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<td>
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<span class="mim-font">
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615185
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Heterotrimeric G proteins, made up of an alpha subunit (see GNAS, 139320), a beta subunit, like GNB4, and a gamma subunit (see GNG2, 606981), relay signals from cell surface receptors to internal effectors. The alpha subunit is a GTPase that interacts in the GDP-bound state with beta-gamma dimers (Rosskopf et al., 2003). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By searching an EST database for G-protein beta-like sequences, followed by 5-prime RACE of a human brain cDNA library, Ruiz-Velasco et al. (2002) cloned GNB4. Like other beta subunits, the deduced GNB4 protein contains 340 amino acids with 7 WD repeat motifs forming a beta-propeller structure. GNB4 shares 91% identity with GNB1 (139380) and 96% identity with mouse Gnb4. PCR analysis detected high GNB4 expression in human lung, pancreas, and placenta, moderate expression in kidney and liver, and weak expression in brain and heart. </p><p>By searching an EST database for sequences similar to mouse Gnb4, followed by PCR of human B lymphoblast and brain RNA, Rosskopf et al. (2003) cloned GNB4. PCR analysis of human, rat, and mouse tissues and cultured cells showed wide GNB4 expression. </p><p>Soong et al. (2013) found that GNB4 colocalized with neurofilament heavy chain and S100 in peripheral human nerves, indicating that it is expressed in both axons and Schwann 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>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>By heterologous overexpression in rat sympathetic neurons, Ruiz-Velasco et al. (2002) found that human G-beta-4 coexpressed with G-gamma-2 (GNG2; 606981) or G-gamma-4 (GNG4; 604388) caused tonic modulation of N-type voltage-gated calcium currents and G protein-gated inwardly rectifying potassium currents. Coexpression of G-beta-4, G-gamma-2 and G-alpha-oA (GNAO1; 139311) resulted in heterotrimer formation. </p><p>Using coprecipitation analysis, Rosskopf et al. (2003) showed that GNB4 formed dimers with all 11 gamma subunits analyzed. The strength of the interaction was variable and was strongest between GNB1 and GNG4, followed by GNG13 (607298) and GNG1 (GNGT1; 189970), and was weakest with GNG8C (GNGT2; 139391). Overexpression of most GNB4-GNG dimers resulted in significant, although sometimes modest, activation of phospholipase beta-2 (PLCB2; 604114), with highest activation by the GNB4-GNG4 dimer. </p><p>Vertebrate retinas have distinct light-on (ON) and light-off (OFF) channels that originate at the level of the retinal bipolar cells. For the conversion from OFF to ON, ON bipolar cells use the GNAO1-coupled glutamate receptor-6 (GRIK2; 138244) such that binding of glutamate suppresses a cation current rather than activating it. Using immunohistochemical analysis and single-cell PCR, Huang et al. (2003) showed that the gamma subunit Gng13 (607298) was coexpressed with the beta subunits Gnb3 (139130) and Gnb4, but no other beta subunit, in dissociated mouse ON bipolar cells. Huang et al. (2003) hypothesized that these G protein subunits selectively participate in signal transduction in ON bipolar cells. </p><p>Soong et al. (2013) found that Gnb4 expression in rats decreased in nerve tissue distal to sciatic nerve transection and increased in nerve tissue after conditioning, suggesting that the protein plays a role in peripheral nerve regeneration. </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 Structure</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>Rosskopf et al. (2003) determined that the GNB4 gene contains 10 exons. The first exon is noncoding. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Rosskopf et al. (2003) mapped the GNB4 gene to chromosome 3. </p><p>Gross (2018) mapped the GNB4 gene to chromosome 3q26.33 based on an alignment of the GNB4 sequence (GenBank AF300648) with the genomic sequence (GRCh38).</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>In affected members of a Han Chinese family with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; 615185) (Lee et al., 2010), Soong et al. (2013) identified a heterozygous mutation in the GNB4 gene (G53D; 610863.0001). The mutation was identified by exome sequencing. An unrelated Han Chinese girl with demyelinating CMT carried a different heterozygous mutation that occurred de novo (K89E; 610863.0002). The frequency of GNB4 mutations in the CMT cohort was 0.8% (2 of 251 families). The phenotype was characterized by onset around adolescence of slowly progressive distal muscle weakness and atrophy affecting the upper and lower limbs, as well as distal sensory impairment and areflexia. In the family, male mutation carriers were more severely affected than female mutation carriers. Immunofluorescence studies of patient sural nerves showed GNB4 staining of onion bulb formations in a rosette pattern. However, immunohistochemical studies showed weaker GNB4 expression in patient sural nerve biopsies compared to controls. Expression of both mutations in COS-7 cells showed that the mutant proteins had impaired bradykinin-induced G protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant proteins were stable in transfected cells, and Soong et al. (2013) postulated a dominant-negative effect. The findings indicated that GNB4-related G protein-coupled receptor signaling is important for proper functioning of peripheral nerves. </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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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
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<strong>2 Selected Examples):</strong>
|
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</span>
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</h4>
|
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0001 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE F</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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GNB4, GLY53ASP
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<br />
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SNP: rs387907340,
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ClinVar: RCV000034850
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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>In affected members of a large 4-generation Han Chinese family with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; 615185), Soong et al. (2013) identified a heterozygous 158G-A transition in the GNB4 gene, resulting in a gly53-to-asp (G53D) substitution at a highly conserved residue. The mutation, which was identified by exome sequencing, segregated with the disorder in the family and was not found in several large control databases, including 1,920 ethnic control chromosomes. The phenotype was characterized by onset around adolescence of slowly progressive distal muscle weakness and atrophy affecting the upper and lower limbs, as well as distal sensory impairment. Male mutation carriers were more severely affected than female mutation carriers. Expression of the mutation in COS-7 cells showed that the mutant protein had impaired bradykinin-induced G-protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant protein was stable in transfected cells, and Soong et al. (2013) postulated a dominant-negative effect. </p>
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<span class="mim-font">
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<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE F</strong>
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<span class="mim-text-font">
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GNB4, LYS89GLU
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<br />
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SNP: rs387907341,
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ClinVar: RCV000034851
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</span>
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<span class="mim-text-font">
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<p>In a 9-year-old Han Chinese girl with dominant intermediate Charcot-Marie-Tooth disease F (CMTDIF; 615185), Soong et al. (2013) identified a de novo heterozygous 265A-G transition in exon 5 of the GNB4 gene, resulting in a lys89-to-glu (K89E) substitution at a highly conserved residue. The mutation was not found in several large control databases, including 1,920 ethnic control chromosomes. Expression of the mutation in COS-7 cells showed that the mutant protein had impaired bradykinin-induced G-protein-coupled receptor intracellular signaling compared to the wildtype protein. The mutant protein was stable in transfected cells, and Soong et al. (2013) postulated a dominant-negative effect. </p>
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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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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 3/9/2018.
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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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Huang, L., Max, M., Margolskee, R. F., Su, H., Masland, R. H., Euler, T.
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<strong>G protein subunit G-gamma-13 is coexpressed with G-alpha-o, G-beta-3, and G-beta-4 in retinal ON bipolar cells.</strong>
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J. Comp. Neurol. 455: 1-10, 2003.
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[PubMed: 12454992]
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[Full Text: https://doi.org/10.1002/cne.10396]
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Lee, Y.-C., Lee, T.-C., Lin, K.-P, Lin, M.-W., Chang, M.-H, Soong, B.-W.
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<strong>Clinical characterization and genetic analysis of a possible novel type of dominant Charcot-Marie-Tooth disease.</strong>
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Neuromusc. Disord. 20: 534-539, 2010.
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[PubMed: 20627571]
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[Full Text: https://doi.org/10.1016/j.nmd.2010.05.001]
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<li>
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<p class="mim-text-font">
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Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W.
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<strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong>
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FEBS Lett. 544: 27-32, 2003.
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[PubMed: 12782285]
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[Full Text: https://doi.org/10.1016/s0014-5793(03)00441-1]
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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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Ruiz-Velasco, V., Ikeda, S. R., Puhl, H. L.
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<strong>Cloning, tissue distribution, and functional expression of the human G protein beta-4-subunit.</strong>
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Physiol. Genomics 8: 41-50, 2002.
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[PubMed: 11842130]
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[Full Text: https://doi.org/10.1152/physiolgenomics.00085.2001]
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<li>
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<p class="mim-text-font">
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Soong, B.-W., Huang, Y.-H., Tsai, P.-C., Huang, C.-C., Pan, H.-C., Lu, Y.-C., Chien, H.-J., Liu, T.-T., Chang, M.-H., Lin, K.-P., Tu, P.-H., Kao, L.-S., Lee, Y.-C.
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<strong>: Exome sequencing identifies GNB4 mutations as a cause of dominant intermediate Charcot-Marie-Tooth disease.</strong>
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Am. J. Hum. Genet. 92: 422-430, 2013.
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[PubMed: 23434117]
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[Full Text: https://doi.org/10.1016/j.ajhg.2013.01.014]
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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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Matthew B. Gross - updated : 03/09/2018<br>Cassandra L. Kniffin - updated : 4/18/2013
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<span class="mim-text-font">
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Patricia A. Hartz : 3/20/2007
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mgross : 03/09/2018<br>carol : 03/07/2018<br>carol : 04/22/2013<br>carol : 4/19/2013<br>ckniffin : 4/18/2013<br>terry : 1/4/2011<br>wwang : 3/20/2007
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