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<title>
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Entry
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- *604943 - SOLUTE CARRIER FAMILY 26, MEMBER 5; SLC26A5
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- OMIM
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604943</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 role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</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" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#evolution">Evolution</a>
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</li>
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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/604943">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=ENSG00000170615;t=ENST00000306312" 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=375611" 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=604943" 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=ENSG00000170615;t=ENST00000306312" 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_001167962,NM_001321787,NM_198999,NM_206883,NM_206884,NM_206885,NR_120441,NR_120442,NR_120443,NR_135801,NR_135802,XM_011516170,XM_047420347,XR_007060034" 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_198999" 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=604943" 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=09224&isoform_id=09224_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/SLC26A5" 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/20139418,30348882,30523029,30523033,30523035,31096302,31096304,39752683,45827800,45827802,45827804,71680166,71681592,71681596,71682632,119603740,119603741,269784651,767947713,1012443753,2217367060,2462614284" 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/P58743" 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=375611" 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=ENSG00000170615;t=ENST00000306312" 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=SLC26A5" 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=SLC26A5" 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+375611" 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/SLC26A5" 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:375611" 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/375611" 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=chr7&hgg_gene=ENST00000306312.8&hgg_start=103352730&hgg_end=103446207&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9359" 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=604943[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=604943[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/ENSG00000170615" 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=SLC26A5" 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=SLC26A5" 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=SLC26A5" 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=SLC26A5&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/PA33731" 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:9359" 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/FBgn0036770.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:1933154" 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/SLC26A5#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:1933154" 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/375611/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=375611" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00010788;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00010788 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00010789;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00010789 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00012259;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00012259 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00017464;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00017464 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00018283;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00018283 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020914;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020914 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-1566" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SLC26A5&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604943
|
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
|
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<span class="mim-font">
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SOLUTE CARRIER FAMILY 26, MEMBER 5; SLC26A5
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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PRESTIN; PRES
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</span>
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</h4>
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</div>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
|
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</span>
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</p>
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</div>
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<div>
|
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<span class="h3 mim-font">
|
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SLC26A5A, INCLUDED
|
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</span>
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</div>
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<div>
|
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<span class="h4 mim-font">
|
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SLC26A5B, INCLUDED<br />
|
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SLC26A5C, INCLUDED<br />
|
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SLC26A5D, INCLUDED
|
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</span>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SLC26A5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC26A5</a></em></strong>
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</span>
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?Deafness, autosomal recessive 61
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PheneGene Graphics <span class="caret"></span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>Prestin is the motor protein of cochlear outer hair cells (<a href="#13" class="mim-tip-reference" title="Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P. <strong>Prestin is the motor protein of cochlear outer hair cells.</strong> Nature 405: 149-155, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10821263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10821263</a>] [<a href="https://doi.org/10.1038/35012009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10821263">Zheng et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10821263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Inasmuch as the most distinguishing feature of this molecular motor is its speed, <a href="#13" class="mim-tip-reference" title="Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P. <strong>Prestin is the motor protein of cochlear outer hair cells.</strong> Nature 405: 149-155, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10821263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10821263</a>] [<a href="https://doi.org/10.1038/35012009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10821263">Zheng et al. (2000)</a> designated it 'prestin' from the musical notation 'presto.' They applied a suppression subtractive hybridization PCR procedure to amplify and enrich the outer hair cell cDNA pool for uniquely expressed gene products from gerbil. Pres fragments in the PCR subtracted library were abundant, at greater than 10% of 487 differentially expressed clones, and showed consistent differential hybridization with outer hair cell- and inner hair cell-derived probes. The full-length clone of gerbil Pres was isolated from an adult gerbil cochlea library. A computer search with the gerbil Pres sequence revealed that about one-third of the human PRES gene had been sequenced as part of the human chromosome 7 effort (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AC005064" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AC005064</a>). The amino acid homology between human and gerbil prestin deduced from the genomic sequence of the first 6 exons is 98%. Prestin has highest homology to members of the family of sulfate/anion transport proteins including pendrin (<a href="/entry/605646">605646</a>) and DRA (downregulated in adenoma; <a href="/entry/126650">126650</a>). Prestin is approximately 40% homologous to pendrin. Northern blot analysis with gerbil mRNA did not detect expression in liver, lung, brain, spleen, ovary, kidney, muscle, or heart. Virtual Northern dot-blot analysis using cDNA prepared from inner hair cells, outer hair cells, mature and newborn organs of Corti, and thyroid revealed expression only in mature outer hair cells and 20-day-old organs of Corti. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10821263" 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="#5" class="mim-tip-reference" title="Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y. <strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong> Hum. Molec. Genet. 12: 1155-1162, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719379</a>] [<a href="https://doi.org/10.1093/hmg/ddg127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719379">Liu et al. (2003)</a> cloned and characterized 4 splicing isoforms of the human SLC26A5 gene, designated SLC26A5A-D, that encode deduced proteins of 744, 685, 516, and 335 amino acids, respectively. SLC26A5A-C contain the complete set of 12 predicted transmembrane domains, whereas SLC26A5D has only 7 of the predicted transmembrane domains. All 4 isoforms preserve the sulfate transport motif, but not the STAS domain. SLC26A5A was the most abundant, adult form of prestin in the cochlea, and the other 3 isoforms were expressed at a lower level and appeared to show different expression during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y. <strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong> Hum. Molec. Genet. 12: 1155-1162, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719379</a>] [<a href="https://doi.org/10.1093/hmg/ddg127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719379">Liu et al. (2003)</a> determined that the SLC26A5 gene contains 21 exons. SLC26A5B-D all share the same terminal 3-prime exon, but differ in their intervening cDNA sequences. SLC26A5A-B share the majority of the sequence and differ only at the terminal 3-prime exon. A consensus polyadenylation signal is present in the 3-prime UTR of SLC26A5B-D, but not in the 3-prime UTR of SLC26A5A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y. <strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong> Hum. Molec. Genet. 12: 1155-1162, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719379</a>] [<a href="https://doi.org/10.1093/hmg/ddg127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719379">Liu et al. (2003)</a> mapped the SLC26A5 gene to chromosome 7q22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#13" class="mim-tip-reference" title="Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P. <strong>Prestin is the motor protein of cochlear outer hair cells.</strong> Nature 405: 149-155, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10821263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10821263</a>] [<a href="https://doi.org/10.1038/35012009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10821263">Zheng et al. (2000)</a> elicited voltage-induced shape changes in cultured human kidney cells that expressed prestin. The mechanical response of outer hair cells to voltage change was accompanied by a 'gating current,' which was manifested as nonlinear capacitance. <a href="#13" class="mim-tip-reference" title="Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P. <strong>Prestin is the motor protein of cochlear outer hair cells.</strong> Nature 405: 149-155, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10821263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10821263</a>] [<a href="https://doi.org/10.1038/35012009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10821263">Zheng et al. (2000)</a> also demonstrated this nonlinear capacitance in transfected kidney cells. They concluded that prestin is the motor protein of cochlear outer hair cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10821263" 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="#9" class="mim-tip-reference" title="Oliver, D., He, D. Z. Z., Klocker, N., Ludwig, J., Schulte, U., Waldegger, S., Ruppersberg, J. P., Dallos, P., Fakler, B. <strong>Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.</strong> Science 292: 2340-2343, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11423665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11423665</a>] [<a href="https://doi.org/10.1126/science.1060939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11423665">Oliver et al. (2001)</a> demonstrated that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ('gating currents') driving the underlying structural rearrangements of the protein. <a href="#9" class="mim-tip-reference" title="Oliver, D., He, D. Z. Z., Klocker, N., Ludwig, J., Schulte, U., Waldegger, S., Ruppersberg, J. P., Dallos, P., Fakler, B. <strong>Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.</strong> Science 292: 2340-2343, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11423665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11423665</a>] [<a href="https://doi.org/10.1126/science.1060939" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11423665">Oliver et al. (2001)</a> suggested a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for the motility of outer hair cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11423665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The most impressive property of outer hair cells (OHCs) in the cochlea is their ability to change their length at high acoustic frequencies, thus providing the exquisite sensitivity and frequency-resolving capacity of the mammalian hearing organ. Prestin appears to be the OHC motor molecule. Homology searches of the coding region of the prestin gene allowed the identification of a thyroid hormone response element (TRE) in the first intron upstream of the prestin ATG start codon (<a href="#12" class="mim-tip-reference" title="Weber, T., Zimmermann, U., Winter, H., Mack, A., Kopschall, I., Rohbock, K., Zenner, H.-P., Knipper, M. <strong>Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.</strong> Proc. Nat. Acad. Sci. 99: 2901-2906, 2002. Note: Erratum: Proc. Nat. Acad. Sci. 99: 7809 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11867734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11867734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11867734[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.052609899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11867734">Weber et al., 2002</a>). Prestin(TRE) bound thyroid hormone receptors (THRA, <a href="/entry/190120">190120</a>; TRHB, <a href="/entry/190160">190160</a>) as a monomer or presumptive heterodimer and mediated a triiodothyronine-dependent transactivation of a heterologous promoter in response to triiodothyronine receptors alpha and beta. Retinoid X receptor-alpha (<a href="/entry/180245">180245</a>) had an additive effect. Expression of prestin mRNA and prestin protein was reduced strongly in the absence of thyroid hormone. On the basis of these data, <a href="#12" class="mim-tip-reference" title="Weber, T., Zimmermann, U., Winter, H., Mack, A., Kopschall, I., Rohbock, K., Zenner, H.-P., Knipper, M. <strong>Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.</strong> Proc. Nat. Acad. Sci. 99: 2901-2906, 2002. Note: Erratum: Proc. Nat. Acad. Sci. 99: 7809 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11867734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11867734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11867734[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.052609899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11867734">Weber et al. (2002)</a> suggested thyroid hormone as a first transcriptional regulator of the motor protein prestin and as a direct or indirect modulator of subcellular prestin distribution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11867734" 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="#2" class="mim-tip-reference" title="Johnson, S. L., Beurg, M., Marcotti, W., Fettiplace, R. <strong>Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant.</strong> Neuron 70: 1143-1154, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689600[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.neuron.2011.04.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689600">Johnson et al. (2011)</a> studied organs of Corti isolated from young rats and gerbils. They found that, at physiologic endolymphatic calcium concentrations, approximately half of the mechanotransducer channels were opened at rest, depolarizing the membrane potential to near -40 mV. This resting potential appeared similar to the membrane potential at which prestin has steepest voltage sensitivity. <a href="#2" class="mim-tip-reference" title="Johnson, S. L., Beurg, M., Marcotti, W., Fettiplace, R. <strong>Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant.</strong> Neuron 70: 1143-1154, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689600[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.neuron.2011.04.024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21689600">Johnson et al. (2011)</a> concluded that minimal time constant filtering ensures optimal prestin activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21689600" 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>Using negatively stained electron microscopy and single-particle analysis, <a href="#7" class="mim-tip-reference" title="Mio, K., Kubo, Y., Ogura, T., Yamamoto, T., Arisaka, F., Sato, C. <strong>The motor protein prestin is a bullet-shaped molecule with inner cavities.</strong> J. Biol. Chem. 283: 1137-1145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998209</a>] [<a href="https://doi.org/10.1074/jbc.M702681200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17998209">Mio et al. (2008)</a> determined the 3-dimensional structure of recombinant full-length rat prestin at 2-nanomolar resolution. Prestin formed tetramers that had an overall bullet shape, with a relatively small extracellular N-terminal end and a large squared cytoplasmic C-terminal domain. Slice images revealed an inner cavity of sparse density. <a href="#7" class="mim-tip-reference" title="Mio, K., Kubo, Y., Ogura, T., Yamamoto, T., Arisaka, F., Sato, C. <strong>The motor protein prestin is a bullet-shaped molecule with inner cavities.</strong> J. Biol. Chem. 283: 1137-1145, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998209</a>] [<a href="https://doi.org/10.1074/jbc.M702681200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17998209">Mio et al. (2008)</a> noted that, although prestin belongs to a family of anion transporters, it does not transport ions across the plasma membrane. Instead, prestin changes its structure by voltage-dependent translocation of anions within the molecule, perhaps via the low-density space within the prestin tetramer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998209" 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="#6" class="mim-tip-reference" title="Minor, J. S., Tang, H.-Y., Pereira, F. A., Alford, R. L. <strong>DNA sequence analysis of SLC26A5, encoding prestin, in a patient-control cohort: identification of fourteen novel DNA sequence variations.</strong> PLoS One 4: e5762, 2009. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19492055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19492055</a>] [<a href="https://doi.org/10.1371/journal.pone.0005762" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19492055">Minor et al. (2009)</a> studied 56 hearing loss patients and 212 controls and identified 23 sequence variations, 21 of which were located in noncoding regions of SLC26A5. Two coding sequence variations, S434S and I663V, were observed only in patients. In silico analysis of the I663V variant suggested that it might be benign. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19492055" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 58 subjects from 15 unrelated Japanese families with hearing loss, <a href="#8" class="mim-tip-reference" title="Mutai, H., Suzuki, N., Shimizu, A., Torii, C., Namba, K., Morimoto, N., Kudoh, J., Kaga, K., Kosaki, K., Matsunaga, T. <strong>Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.</strong> Orphanet J. Rare Dis. 8: 172, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24164807[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/10.1186/1750-1172-8-172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164807">Mutai et al. (2013)</a> identified 2 sisters who were compound heterozygous for mutations in the SLC26A5 gene: a missense mutation (R130S; <a href="#0002">604943.0002</a>) inherited from their mother, and a nonsense mutation (W70X; <a href="#0003">604943.0003</a>) inherited from their father. The mutations were not found in the dbSNP (build 135), 1000 Genomes Project, or Exome Variant Server databases, and the R130S mutation was not found in 192 Japanese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164807" 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="Liberman, M. C., Gao, J., He, D. Z. Z., Wu, X., Jia, S., Zuo, J. <strong>Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.</strong> Nature 419: 300-304, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12239568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12239568</a>] [<a href="https://doi.org/10.1038/nature01059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12239568">Liberman et al. (2002)</a> created mice deficient in prestin by targeted disruption. Homozygous mutant mice had a loss of outer hair cell electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo, without disruption of mechanoelectrical transduction in outer hair cells. In heterozygotes, electromotility was halved and there was a 2-fold (about 6 dB) increase in cochlear thresholds. <a href="#4" class="mim-tip-reference" title="Liberman, M. C., Gao, J., He, D. Z. Z., Wu, X., Jia, S., Zuo, J. <strong>Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.</strong> Nature 419: 300-304, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12239568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12239568</a>] [<a href="https://doi.org/10.1038/nature01059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12239568">Liberman et al. (2002)</a> concluded that prestin is the motor protein required for electromotility, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12239568" 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 a knockin mouse model, <a href="#1" class="mim-tip-reference" title="Homma, K., Duan, C., Zheng, J., Cheatham, M. A., Dallos, P. <strong>The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.</strong> J. Biol. Chem. 288: 2452-2463, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23212912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23212912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23212912[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/10.1074/jbc.M112.411579" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23212912">Homma et al. (2013)</a> showed that substitution of val499 with gly (V499G) drastically altered the electromotility of mouse prestin. V499 was predicted to reside near the C-terminal end of the last transmembrane segment, immediately preceding the intracellular C-terminal domain. V499G mutant prestin was targeted appropriately to membranes and formed heterotetramers with wildtype prestin. The motor function of prestin was not affected by multimer formation, suggesting functional independence of prestin subunits within multimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23212912" 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 studying the phylogenetic history and molecular evolution of the prestin gene in mammals, <a href="#3" class="mim-tip-reference" title="Li, G., Wang, J., Rossiter, S. J., Jones, G., Cotton, J. A., Zhang, S. <strong>The hearing gene Prestin reunites echolocating bats.</strong> Proc. Nat. Acad. Sci. 105: 13959-13964, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18776049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18776049</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18776049[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0802097105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18776049">Li et al. (2008)</a> found evidence that prestin has undergone positive selection associated with the evolution of high frequency hearing in echolocating bats. Over 80% of the sites under positive selection occur in functionally important regions, including those involved in voltage sensing, sulfate transport, and protein targeting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18776049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs116900495 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs116900495;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs116900495?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs116900495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs116900495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005607 OR RCV000425160 OR RCV003311651" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005607, RCV000425160, RCV003311651" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005607...</a>
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<p>This variant, formerly titled DEAFNESS, AUTOSOMAL RECESSIVE 61, has been reclassified based on the findings of <a href="#11" class="mim-tip-reference" title="Tang, H.-Y., Xia, A., Oghalai, J. S., Pereira, F. A., Alford, R. L. <strong>High frequency of the IVS2-2A-G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.</strong> BMC Med. Genet. 6: 30, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086836</a>] [<a href="https://doi.org/10.1186/1471-2350-6-30" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16086836">Tang et al. (2005)</a> and <a href="#10" class="mim-tip-reference" title="Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others. <strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong> Am. J. Hum. Genet. 95: 445-453, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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.2014.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25262649">Shearer et al. (2014)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16086836+25262649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 of 220 Caucasian probands with nonsyndromic deafness (DFNB61; <a href="/entry/613865">613865</a>), <a href="#5" class="mim-tip-reference" title="Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y. <strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong> Hum. Molec. Genet. 12: 1155-1162, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719379</a>] [<a href="https://doi.org/10.1093/hmg/ddg127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719379">Liu et al. (2003)</a> identified a homozygous A-to-G transition at position -2 in intron 2 of the PRES gene, resulting in aberrant splicing. One of the 2 probands was born to nonconsanguineous parents in a simplex sibship, whereas the other was born to consanguineous parents in a multiplex sibship in which 2 sibs were also reported as deaf but who were unavailable for testing. In addition, heterozygosity for this mutation was observed in 7 (3%) of the 220 probands, suggesting the possibility of semidominant influence of the mutation in causing hearing loss. The mutation was not found in 250 Caucasian control subjects. No mutation in the SLC26A5 gene was found in 150 deaf probands from other ethnic backgrounds, suggesting an association with a specific ethnic background. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 84 hearing-impaired individuals and 246 Caucasian and Hispanic controls, <a href="#11" class="mim-tip-reference" title="Tang, H.-Y., Xia, A., Oghalai, J. S., Pereira, F. A., Alford, R. L. <strong>High frequency of the IVS2-2A-G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.</strong> BMC Med. Genet. 6: 30, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086836</a>] [<a href="https://doi.org/10.1186/1471-2350-6-30" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16086836">Tang et al. (2005)</a> identified 4 hearing-impaired individuals and 4 controls who were heterozygous for the IVS2-2A-G mutation. They did not find the mutation in homozygous state in any of the 330 subjects. <a href="#11" class="mim-tip-reference" title="Tang, H.-Y., Xia, A., Oghalai, J. S., Pereira, F. A., Alford, R. L. <strong>High frequency of the IVS2-2A-G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.</strong> BMC Med. Genet. 6: 30, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086836</a>] [<a href="https://doi.org/10.1186/1471-2350-6-30" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16086836">Tang et al. (2005)</a> stated that the allele frequency of the IVS2-2A-G variant was not statistically significantly different between cases and controls, thus challenging whether it was associated with hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16086836" 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>Based on allele frequency in 8,595 controls from 12 populations (maximum minor allele frequency = 0.0156), <a href="#10" class="mim-tip-reference" title="Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others. <strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong> Am. J. Hum. Genet. 95: 445-453, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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.2014.09.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25262649">Shearer et al. (2014)</a> recategorized the c.-53-2A-G variant in the SLC26A5 gene as benign. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25262649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs431905517 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs431905517;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs431905517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs431905517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000083266" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000083266" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000083266</a>
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<p>In 2 Japanese sisters, aged 6 and 9 years, with moderate to severe hearing loss (family 3), <a href="#8" class="mim-tip-reference" title="Mutai, H., Suzuki, N., Shimizu, A., Torii, C., Namba, K., Morimoto, N., Kudoh, J., Kaga, K., Kosaki, K., Matsunaga, T. <strong>Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.</strong> Orphanet J. Rare Dis. 8: 172, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24164807[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/10.1186/1750-1172-8-172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164807">Mutai et al. (2013)</a> identified compound heterozygosity for 2 mutations in the SLC26A5 gene: a c.390A-C transversion, resulting in an arg130-to-ser (R130S) substitution, inherited from their mother, and a c.209G-A transition, resulting in a trp70-to-ter (W70X; <a href="#0003">604943.0003</a>) substitution, inherited from their father. These mutations were not found in the dbSNP (build 135), 1000 Genomes Project, or NHLBI Exome Sequencing Project databases. The c.390A-C mutation was not found in 192 Japanese controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs431905518 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs431905518;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs431905518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs431905518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the trp70-to-ter (W70X) mutation in the SLC26A5 gene that was found in compound heterozygous state in Japanese sisters with autosomal recessive hearing loss (DFNB61; <a href="/entry/613865">613865</a>) by <a href="#8" class="mim-tip-reference" title="Mutai, H., Suzuki, N., Shimizu, A., Torii, C., Namba, K., Morimoto, N., Kudoh, J., Kaga, K., Kosaki, K., Matsunaga, T. <strong>Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.</strong> Orphanet J. Rare Dis. 8: 172, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24164807[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/10.1186/1750-1172-8-172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24164807">Mutai et al. (2013)</a>, see <a href="#0002">604943.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24164807" 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>The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.</strong>
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J. Biol. Chem. 288: 2452-2463, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23212912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23212912</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23212912[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=23212912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M112.411579" target="_blank">Full Text</a>]
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<strong>Prestin-driven cochlear amplification is not limited by the outer hair cell membrane time constant.</strong>
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Neuron 70: 1143-1154, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21689600/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21689600</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21689600[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=21689600" 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.neuron.2011.04.024" target="_blank">Full Text</a>]
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Li, G., Wang, J., Rossiter, S. J., Jones, G., Cotton, J. A., Zhang, S.
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<strong>The hearing gene Prestin reunites echolocating bats.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 13959-13964, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18776049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18776049</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18776049[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=18776049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0802097105" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Liberman2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Liberman, M. C., Gao, J., He, D. Z. Z., Wu, X., Jia, S., Zuo, J.
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<strong>Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.</strong>
|
|
Nature 419: 300-304, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12239568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12239568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12239568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature01059" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Liu2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y.
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|
<strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong>
|
|
Hum. Molec. Genet. 12: 1155-1162, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719379</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719379" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg127" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Minor2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Minor, J. S., Tang, H.-Y., Pereira, F. A., Alford, R. L.
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<strong>DNA sequence analysis of SLC26A5, encoding prestin, in a patient-control cohort: identification of fourteen novel DNA sequence variations.</strong>
|
|
PLoS One 4: e5762, 2009. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19492055/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19492055</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19492055" 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/10.1371/journal.pone.0005762" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Mio2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mio, K., Kubo, Y., Ogura, T., Yamamoto, T., Arisaka, F., Sato, C.
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<strong>The motor protein prestin is a bullet-shaped molecule with inner cavities.</strong>
|
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J. Biol. Chem. 283: 1137-1145, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17998209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17998209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17998209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M702681200" target="_blank">Full Text</a>]
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Mutai2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mutai, H., Suzuki, N., Shimizu, A., Torii, C., Namba, K., Morimoto, N., Kudoh, J., Kaga, K., Kosaki, K., Matsunaga, T.
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<strong>Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patients: a cross-sectional, multi-center next-generation sequencing study.</strong>
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Orphanet J. Rare Dis. 8: 172, 2013. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24164807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24164807</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24164807[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=24164807" 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/10.1186/1750-1172-8-172" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Oliver2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Oliver, D., He, D. Z. Z., Klocker, N., Ludwig, J., Schulte, U., Waldegger, S., Ruppersberg, J. P., Dallos, P., Fakler, B.
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<strong>Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.</strong>
|
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Science 292: 2340-2343, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11423665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11423665</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11423665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1060939" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Shearer2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others.
|
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<strong>Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.</strong>
|
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Am. J. Hum. Genet. 95: 445-453, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25262649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25262649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25262649[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=25262649" 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.2014.09.001" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Tang2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tang, H.-Y., Xia, A., Oghalai, J. S., Pereira, F. A., Alford, R. L.
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<strong>High frequency of the IVS2-2A-G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss.</strong>
|
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BMC Med. Genet. 6: 30, 2005. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16086836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16086836</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16086836" 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/10.1186/1471-2350-6-30" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Weber2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weber, T., Zimmermann, U., Winter, H., Mack, A., Kopschall, I., Rohbock, K., Zenner, H.-P., Knipper, M.
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<strong>Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 2901-2906, 2002. Note: Erratum: Proc. Nat. Acad. Sci. 99: 7809 only, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11867734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11867734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11867734[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=11867734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.052609899" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Zheng2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P.
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<strong>Prestin is the motor protein of cochlear outer hair cells.</strong>
|
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Nature 405: 149-155, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10821263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10821263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10821263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/35012009" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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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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Ada Hamosh - updated : 10/28/2014
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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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Patricia A. Hartz - updated : 2/6/2014<br>Joanna S. Amberger - updated : 2/4/2014<br>Patricia A. Hartz - updated : 8/28/2009<br>George E. Tiller - updated : 2/25/2005<br>Ada Hamosh - updated : 9/17/2002<br>Victor A. McKusick - updated : 4/16/2002<br>Ada Hamosh - updated : 6/27/2001
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh : 5/10/2000
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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 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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carol : 09/05/2024
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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 : 07/17/2020<br>carol : 04/06/2017<br>carol : 09/30/2016<br>carol : 06/09/2015<br>alopez : 10/28/2014<br>alopez : 10/28/2014<br>carol : 2/19/2014<br>carol : 2/18/2014<br>carol : 2/17/2014<br>carol : 2/10/2014<br>mgross : 2/6/2014<br>carol : 2/6/2014<br>mcolton : 2/5/2014<br>joanna : 2/4/2014<br>carol : 4/12/2013<br>carol : 4/4/2011<br>mgross : 9/4/2009<br>terry : 8/28/2009<br>joanna : 2/25/2009<br>terry : 12/12/2008<br>wwang : 10/10/2007<br>alopez : 7/13/2007<br>tkritzer : 3/18/2005<br>tkritzer : 3/8/2005<br>terry : 2/25/2005<br>alopez : 9/20/2002<br>alopez : 9/17/2002<br>alopez : 4/26/2002<br>terry : 4/16/2002<br>alopez : 7/3/2001<br>terry : 6/27/2001<br>alopez : 2/20/2001<br>carol : 6/13/2000<br>alopez : 5/10/2000<br>carol : 5/10/2000
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<span class="mim-font">
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<strong>*</strong> 604943
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<div>
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<h3>
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<span class="mim-font">
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SOLUTE CARRIER FAMILY 26, MEMBER 5; SLC26A5
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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PRESTIN; PRES
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</span>
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</h4>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
|
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SLC26A5A, INCLUDED
|
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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SLC26A5B, INCLUDED<br />
|
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SLC26A5C, INCLUDED<br />
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SLC26A5D, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: SLC26A5</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
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Cytogenetic location: 7q22.1
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|
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:103,352,730-103,446,207 </span>
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<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>
|
|
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>
|
|
Inheritance
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|
</th>
|
|
<th>
|
|
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>
|
|
<td rowspan="1">
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<span class="mim-font">
|
|
7q22.1
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
?Deafness, autosomal recessive 61
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</span>
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</td>
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<td>
|
|
<span class="mim-font">
|
|
613865
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|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
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|
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</tr>
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|
|
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|
|
</tbody>
|
|
</table>
|
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</div>
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</div>
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<div>
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<br />
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|
</div>
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<div>
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|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
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</h4>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Prestin is the motor protein of cochlear outer hair cells (Zheng et al., 2000). </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<span class="mim-text-font">
|
|
<p>The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Inasmuch as the most distinguishing feature of this molecular motor is its speed, Zheng et al. (2000) designated it 'prestin' from the musical notation 'presto.' They applied a suppression subtractive hybridization PCR procedure to amplify and enrich the outer hair cell cDNA pool for uniquely expressed gene products from gerbil. Pres fragments in the PCR subtracted library were abundant, at greater than 10% of 487 differentially expressed clones, and showed consistent differential hybridization with outer hair cell- and inner hair cell-derived probes. The full-length clone of gerbil Pres was isolated from an adult gerbil cochlea library. A computer search with the gerbil Pres sequence revealed that about one-third of the human PRES gene had been sequenced as part of the human chromosome 7 effort (GenBank AC005064). The amino acid homology between human and gerbil prestin deduced from the genomic sequence of the first 6 exons is 98%. Prestin has highest homology to members of the family of sulfate/anion transport proteins including pendrin (605646) and DRA (downregulated in adenoma; 126650). Prestin is approximately 40% homologous to pendrin. Northern blot analysis with gerbil mRNA did not detect expression in liver, lung, brain, spleen, ovary, kidney, muscle, or heart. Virtual Northern dot-blot analysis using cDNA prepared from inner hair cells, outer hair cells, mature and newborn organs of Corti, and thyroid revealed expression only in mature outer hair cells and 20-day-old organs of Corti. </p><p>Liu et al. (2003) cloned and characterized 4 splicing isoforms of the human SLC26A5 gene, designated SLC26A5A-D, that encode deduced proteins of 744, 685, 516, and 335 amino acids, respectively. SLC26A5A-C contain the complete set of 12 predicted transmembrane domains, whereas SLC26A5D has only 7 of the predicted transmembrane domains. All 4 isoforms preserve the sulfate transport motif, but not the STAS domain. SLC26A5A was the most abundant, adult form of prestin in the cochlea, and the other 3 isoforms were expressed at a lower level and appeared to show different expression during development. </p>
|
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</span>
|
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<div>
|
|
<br />
|
|
</div>
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|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Liu et al. (2003) determined that the SLC26A5 gene contains 21 exons. SLC26A5B-D all share the same terminal 3-prime exon, but differ in their intervening cDNA sequences. SLC26A5A-B share the majority of the sequence and differ only at the terminal 3-prime exon. A consensus polyadenylation signal is present in the 3-prime UTR of SLC26A5B-D, but not in the 3-prime UTR of SLC26A5A. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Liu et al. (2003) mapped the SLC26A5 gene to chromosome 7q22.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zheng et al. (2000) elicited voltage-induced shape changes in cultured human kidney cells that expressed prestin. The mechanical response of outer hair cells to voltage change was accompanied by a 'gating current,' which was manifested as nonlinear capacitance. Zheng et al. (2000) also demonstrated this nonlinear capacitance in transfected kidney cells. They concluded that prestin is the motor protein of cochlear outer hair cells. </p><p>Oliver et al. (2001) demonstrated that voltage sensitivity is conferred to prestin by the intracellular anions chloride and bicarbonate. Removal of these anions abolished fast voltage-dependent motility, as well as the characteristic nonlinear charge movement ('gating currents') driving the underlying structural rearrangements of the protein. Oliver et al. (2001) suggested a model in which anions act as extrinsic voltage sensors, which bind to the prestin molecule and thus trigger the conformational changes required for the motility of outer hair cells. </p><p>The most impressive property of outer hair cells (OHCs) in the cochlea is their ability to change their length at high acoustic frequencies, thus providing the exquisite sensitivity and frequency-resolving capacity of the mammalian hearing organ. Prestin appears to be the OHC motor molecule. Homology searches of the coding region of the prestin gene allowed the identification of a thyroid hormone response element (TRE) in the first intron upstream of the prestin ATG start codon (Weber et al., 2002). Prestin(TRE) bound thyroid hormone receptors (THRA, 190120; TRHB, 190160) as a monomer or presumptive heterodimer and mediated a triiodothyronine-dependent transactivation of a heterologous promoter in response to triiodothyronine receptors alpha and beta. Retinoid X receptor-alpha (180245) had an additive effect. Expression of prestin mRNA and prestin protein was reduced strongly in the absence of thyroid hormone. On the basis of these data, Weber et al. (2002) suggested thyroid hormone as a first transcriptional regulator of the motor protein prestin and as a direct or indirect modulator of subcellular prestin distribution. </p><p>Johnson et al. (2011) studied organs of Corti isolated from young rats and gerbils. They found that, at physiologic endolymphatic calcium concentrations, approximately half of the mechanotransducer channels were opened at rest, depolarizing the membrane potential to near -40 mV. This resting potential appeared similar to the membrane potential at which prestin has steepest voltage sensitivity. Johnson et al. (2011) concluded that minimal time constant filtering ensures optimal prestin activation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using negatively stained electron microscopy and single-particle analysis, Mio et al. (2008) determined the 3-dimensional structure of recombinant full-length rat prestin at 2-nanomolar resolution. Prestin formed tetramers that had an overall bullet shape, with a relatively small extracellular N-terminal end and a large squared cytoplasmic C-terminal domain. Slice images revealed an inner cavity of sparse density. Mio et al. (2008) noted that, although prestin belongs to a family of anion transporters, it does not transport ions across the plasma membrane. Instead, prestin changes its structure by voltage-dependent translocation of anions within the molecule, perhaps via the low-density space within the prestin tetramer. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Minor et al. (2009) studied 56 hearing loss patients and 212 controls and identified 23 sequence variations, 21 of which were located in noncoding regions of SLC26A5. Two coding sequence variations, S434S and I663V, were observed only in patients. In silico analysis of the I663V variant suggested that it might be benign. </p><p>In a study of 58 subjects from 15 unrelated Japanese families with hearing loss, Mutai et al. (2013) identified 2 sisters who were compound heterozygous for mutations in the SLC26A5 gene: a missense mutation (R130S; 604943.0002) inherited from their mother, and a nonsense mutation (W70X; 604943.0003) inherited from their father. The mutations were not found in the dbSNP (build 135), 1000 Genomes Project, or Exome Variant Server databases, and the R130S mutation was not found in 192 Japanese controls. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Liberman et al. (2002) created mice deficient in prestin by targeted disruption. Homozygous mutant mice had a loss of outer hair cell electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo, without disruption of mechanoelectrical transduction in outer hair cells. In heterozygotes, electromotility was halved and there was a 2-fold (about 6 dB) increase in cochlear thresholds. Liberman et al. (2002) concluded that prestin is the motor protein required for electromotility, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear. </p><p>Using a knockin mouse model, Homma et al. (2013) showed that substitution of val499 with gly (V499G) drastically altered the electromotility of mouse prestin. V499 was predicted to reside near the C-terminal end of the last transmembrane segment, immediately preceding the intracellular C-terminal domain. V499G mutant prestin was targeted appropriately to membranes and formed heterotetramers with wildtype prestin. The motor function of prestin was not affected by multimer formation, suggesting functional independence of prestin subunits within multimers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Evolution</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By studying the phylogenetic history and molecular evolution of the prestin gene in mammals, Li et al. (2008) found evidence that prestin has undergone positive selection associated with the evolution of high frequency hearing in echolocating bats. Over 80% of the sites under positive selection occur in functionally important regions, including those involved in voltage sensing, sulfate transport, and protein targeting. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>3 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A5, IVS2AS, A-G, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs116900495,
|
|
|
|
|
|
gnomAD: rs116900495,
|
|
|
|
|
|
ClinVar: RCV000005607, RCV000425160, RCV003311651
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled DEAFNESS, AUTOSOMAL RECESSIVE 61, has been reclassified based on the findings of Tang et al. (2005) and Shearer et al. (2014). </p><p>In 2 of 220 Caucasian probands with nonsyndromic deafness (DFNB61; 613865), Liu et al. (2003) identified a homozygous A-to-G transition at position -2 in intron 2 of the PRES gene, resulting in aberrant splicing. One of the 2 probands was born to nonconsanguineous parents in a simplex sibship, whereas the other was born to consanguineous parents in a multiplex sibship in which 2 sibs were also reported as deaf but who were unavailable for testing. In addition, heterozygosity for this mutation was observed in 7 (3%) of the 220 probands, suggesting the possibility of semidominant influence of the mutation in causing hearing loss. The mutation was not found in 250 Caucasian control subjects. No mutation in the SLC26A5 gene was found in 150 deaf probands from other ethnic backgrounds, suggesting an association with a specific ethnic background. </p><p>In a study of 84 hearing-impaired individuals and 246 Caucasian and Hispanic controls, Tang et al. (2005) identified 4 hearing-impaired individuals and 4 controls who were heterozygous for the IVS2-2A-G mutation. They did not find the mutation in homozygous state in any of the 330 subjects. Tang et al. (2005) stated that the allele frequency of the IVS2-2A-G variant was not statistically significantly different between cases and controls, thus challenging whether it was associated with hearing loss. </p><p>Based on allele frequency in 8,595 controls from 12 populations (maximum minor allele frequency = 0.0156), Shearer et al. (2014) recategorized the c.-53-2A-G variant in the SLC26A5 gene as benign. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 61 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A5, ARG130SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs431905517,
|
|
|
|
|
|
|
|
ClinVar: RCV000083266
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Japanese sisters, aged 6 and 9 years, with moderate to severe hearing loss (family 3), Mutai et al. (2013) identified compound heterozygosity for 2 mutations in the SLC26A5 gene: a c.390A-C transversion, resulting in an arg130-to-ser (R130S) substitution, inherited from their mother, and a c.209G-A transition, resulting in a trp70-to-ter (W70X; 604943.0003) substitution, inherited from their father. These mutations were not found in the dbSNP (build 135), 1000 Genomes Project, or NHLBI Exome Sequencing Project databases. The c.390A-C mutation was not found in 192 Japanese controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 DEAFNESS, AUTOSOMAL RECESSIVE 61 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SLC26A5, TRP70TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs431905518,
|
|
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|
|
|
|
|
ClinVar: RCV000083267
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp70-to-ter (W70X) mutation in the SLC26A5 gene that was found in compound heterozygous state in Japanese sisters with autosomal recessive hearing loss (DFNB61; 613865) by Mutai et al. (2013), see 604943.0002. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Homma, K., Duan, C., Zheng, J., Cheatham, M. A., Dallos, P.
|
|
<strong>The V499G/Y501H mutation impairs fast motor kinetics of prestin and has significance for defining functional independence of individual prestin subunits.</strong>
|
|
J. Biol. Chem. 288: 2452-2463, 2013.
|
|
|
|
|
|
[PubMed: 23212912]
|
|
|
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|
|
[Full Text: https://doi.org/10.1074/jbc.M112.411579]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Li, G., Wang, J., Rossiter, S. J., Jones, G., Cotton, J. A., Zhang, S.
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Liberman, M. C., Gao, J., He, D. Z. Z., Wu, X., Jia, S., Zuo, J.
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<strong>Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.</strong>
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Nature 419: 300-304, 2002.
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Liu, X. Z., Ouyang, X. M., Xia, X. J., Zheng, J., Pandya, A., Li, F., Du, L. L., Welch, K. O., Petit, C., Smith, R. J. H., Webb, B. T., Yan, D., Arnos, K. S., Corey, D., Dallos, P., Nance, W. E., Chen, Z. Y.
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<strong>Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss.</strong>
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Minor, J. S., Tang, H.-Y., Pereira, F. A., Alford, R. L.
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<strong>DNA sequence analysis of SLC26A5, encoding prestin, in a patient-control cohort: identification of fourteen novel DNA sequence variations.</strong>
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Mio, K., Kubo, Y., Ogura, T., Yamamoto, T., Arisaka, F., Sato, C.
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<strong>The motor protein prestin is a bullet-shaped molecule with inner cavities.</strong>
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J. Biol. Chem. 283: 1137-1145, 2008.
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Mutai, H., Suzuki, N., Shimizu, A., Torii, C., Namba, K., Morimoto, N., Kudoh, J., Kaga, K., Kosaki, K., Matsunaga, T.
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Oliver, D., He, D. Z. Z., Klocker, N., Ludwig, J., Schulte, U., Waldegger, S., Ruppersberg, J. P., Dallos, P., Fakler, B.
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<strong>Intracellular anions as the voltage sensor of prestin, the outer hair cell motor protein.</strong>
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Science 292: 2340-2343, 2001.
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Shearer, A. E., Eppsteiner, R. W., Booth, K. T., Ephraim, S. S., Gurrola, J., II, Simpson, A., Black-Ziegelbein, E. A., Joshi, S., Ravi, H., Giuffre, A. C., Happe, S., Hildebrand, M. S., and 20 others.
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Tang, H.-Y., Xia, A., Oghalai, J. S., Pereira, F. A., Alford, R. L.
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Weber, T., Zimmermann, U., Winter, H., Mack, A., Kopschall, I., Rohbock, K., Zenner, H.-P., Knipper, M.
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<strong>Thyroid hormone is a critical determinant for the regulation of the cochlear motor protein prestin.</strong>
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Zheng, J., Shen, W., He, D. Z. Z., Long, K. B., Madison, L. D., Dallos, P.
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