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<title>
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Entry
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- *142600 - HEXOKINASE 1; HK1
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*142600</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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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/142600">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></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=ENSG00000156515;t=ENST00000359426" 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=3098" 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=142600" 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=ENSG00000156515;t=ENST00000359426" 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_000188,NM_001322364,NM_001322365,NM_001322366,NM_001322367,NM_001358263,NM_033496,NM_033497,NM_033498,NM_033500,XM_024447969,XM_047425136,XM_047425137,XM_047425139" 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_000188" 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=142600" 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=00809&isoform_id=00809_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/HK1" 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/34670,184021,1777449,1777451,1777453,2827147,2827148,2873349,2873350,3283998,8996017,8996018,14250554,15991827,15991829,15991831,62088632,116242516,119574704,119574705,119574706,119574707,119574708,158257456,188497750,188497754,193785864,193787115,194377450,1016841067,1016841071,1016841120,1016841124,1279500937,1370456959,2217276930,2217276932,2217276934,2462518819,2462518821,2462518823,2462518825" 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/P19367" 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=3098" 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=ENSG00000156515;t=ENST00000359426" 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=HK1" 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=HK1" 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+3098" 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/HK1" 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:3098" 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/3098" 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=chr10&hgg_gene=ENST00000643399.2&hgg_start=69270000&hgg_end=69401882&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=142600[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=142600[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://www.deciphergenomics.org/gene/HK1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000156515" 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=HK1" 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=HK1" 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=HK1" 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=HK1&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/PA29300" 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:4922" 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/FBgn0001186.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:96103" 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/HK1#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:96103" 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/3098/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=3098" 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=WBGene00008780;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00008780 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00010416;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00010416 </a></div>
|
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-2848" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
|
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3098" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HK1&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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715799004<br />
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">ICD+</a>
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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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142600
|
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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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HEXOKINASE 1; HK1
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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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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HK1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HK1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/10/260?start=-3&limit=10&highlight=260">10q22.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:69270000-69401882&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">10:69,270,000-69,401,882</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
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Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=235700,618547,605285,617460" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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10q22.1
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Anemia, congenital, nonspherocytic hemolytic, 5, hexokinase deficient
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<a href="/entry/235700"> 235700 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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Neurodevelopmental disorder with visual defects and brain anomalies
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<a href="/entry/618547"> 618547 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Neuropathy, hereditary motor and sensory, Russe type
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<a href="/entry/605285"> 605285 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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Retinitis pigmentosa 79
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<a href="/entry/617460"> 617460 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/142600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/142600" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>Hexokinase (<a href="https://enzyme.expasy.org/EC/2.7.1.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.7.1.1</a>) catalyzes the first step in glucose metabolism, using ATP for the phosphorylation of glucose to glucose-6-phosphate. Four different forms of hexokinase, designated type HK1, HK2 (<a href="/entry/601125">601125</a>), HK3 (<a href="/entry/142570">142570</a>), and HK4 (<a href="/entry/138079">138079</a>), encoded by different genes, are present in mammalian tissues. Among these, HK1 is the predominant glucose phosphorylating activity in those tissues that share a strict dependence on glucose utilization for their physiologic functions, such as brain, erythrocytes, platelets, lymphocytes, and fibroblasts (summary by <a href="#3" class="mim-tip-reference" title="Bianchi, M., Crinelli, R., Serafini, G. Giammarini, C., Magnani, M. <strong>Molecular bases of hexokinase deficiency.</strong> Biochim. Biophys. Acta 1360: 211-221, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9197463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9197463</a>] [<a href="https://doi.org/10.1016/s0925-4439(96)00080-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9197463">Bianchi et al., 1997</a>). Different isoforms of HK1 are either cytoplasmic or associated with the outer mitochondrial membrane (OMM) through a 5-prime porin (VDAC1; <a href="/entry/604492">604492</a>)-binding domain (<a href="#18" class="mim-tip-reference" title="Murakami, K., Piomelli, S. <strong>Identification of the cDNA for human red blood cell-specific hexokinase isozyme.</strong> Blood 89: 762-766, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9028305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9028305</a>]" pmid="9028305">Murakami and Piomelli, 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9197463+9028305" 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>Cloning and Expression</strong>
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<p><a href="#19" class="mim-tip-reference" title="Nishi, S., Seino, S., Bell, G. I. <strong>Human hexokinase: sequences of amino- and carboxyl-terminal halves are homologous.</strong> Biochem. Biophys. Res. Commun. 157: 937-943, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3207429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3207429</a>] [<a href="https://doi.org/10.1016/s0006-291x(88)80964-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3207429">Nishi et al. (1988)</a> analyzed cDNA clones encoding human hexokinase isolated from an adult kidney library. Analysis of this 917-amino acid protein showed that the sequences of the N- and C-terminal halves, corresponding to the regulatory and catalytic domains, respectively, are homologous. Eukaryotic hexokinases evolved from duplication of a gene encoding a protein of about 450 amino acids. <a href="#13" class="mim-tip-reference" title="Griffin, L. D., Gelb, B. D., Wheeler, D. A., Davison, D., Adams, V., McCabe, E. R. B. <strong>Mammalian hexokinase 1: evolutionary conservation and structure to function analysis.</strong> Genomics 11: 1014-1024, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783373</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90027-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783373">Griffin et al. (1991)</a> thought that comparisons of sequences in many species supported the theory of <a href="#31" class="mim-tip-reference" title="Ureta, T. <strong>The comparative isozymology of vertebrate hexokinases.</strong> Comp. Biochem. Physiol. B 71: 549-555, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7044667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7044667</a>] [<a href="https://doi.org/10.1016/0305-0491(82)90461-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7044667">Ureta (1982)</a> that the mammalian hexokinases arose from the duplication and fusion of an ancestral protoenzyme and that the yeast and mammalian glucokinases arose twice in evolution. Sequence analysis demonstrated that a 15-amino acid porin-binding domain in the N terminus of HK1 is absolutely conserved and mediates the binding of HK1 to the mitochondria. In the course of their work, <a href="#13" class="mim-tip-reference" title="Griffin, L. D., Gelb, B. D., Wheeler, D. A., Davison, D., Adams, V., McCabe, E. R. B. <strong>Mammalian hexokinase 1: evolutionary conservation and structure to function analysis.</strong> Genomics 11: 1014-1024, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1783373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1783373</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90027-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1783373">Griffin et al. (1991)</a> developed a method for cloning the cDNA for a low abundance protein using knowledge of the evolutionary conservation of amino acid and nucleotide sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3207429+7044667+1783373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By liquid chromatography, <a href="#17" class="mim-tip-reference" title="Murakami, K., Blei, F., Tilton, W., Seaman, C., Piomelli, S. <strong>An isozyme of hexokinase specific for the human red blood cell (HK-R).</strong> Blood 75: 770-775, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2297576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2297576</a>]" pmid="2297576">Murakami et al. (1990)</a> identified 2 distinct major isozymes of human red blood cell (RBC) hexokinase. One had a molecular mass similar to that of HK1 identified in liver, and the other, designated HKR, was larger than HK1 by several kilodaltons. RBC from normal blood contained HK1 and HKR at an equal activity, but in reticulocyte-rich RBC, HKR dominated. <a href="#18" class="mim-tip-reference" title="Murakami, K., Piomelli, S. <strong>Identification of the cDNA for human red blood cell-specific hexokinase isozyme.</strong> Blood 89: 762-766, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9028305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9028305</a>]" pmid="9028305">Murakami and Piomelli (1997)</a> isolated a cDNA clone for the red cell-specific HK isozyme HKR. Its nucleotide sequence was identical to HK1 cDNA except for the 5-prime end. It lacks the first 62 nucleotides of the HK1 coding region; instead, it contains a unique sequence of 60 nucleotides at the beginning of the coding sequence as well as another unique sequence upstream of the putative translation initiation site. It lacks the porin-binding domain that facilitates binding to mitochondria, thus explaining the exclusive cytoplasmic localization of red blood cell HK. Northern blot analysis showed that it was expressed in reticulocytes and in an erythroleukemic cell line, but not in a lymphocytic cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9028305+2297576" 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="#15" class="mim-tip-reference" title="Mori, C., Nakamura, N., Welch, J. E., Shiota, K., Eddy, E. M. <strong>Testis-specific expression of mRNAs for a unique human type 1 hexokinase lacking the porin-binding domain.</strong> Molec. Reprod. Dev. 44: 14-22, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8722688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8722688</a>] [<a href="https://doi.org/10.1002/(SICI)1098-2795(199605)44:1<14::AID-MRD2>3.0.CO;2-W" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8722688">Mori et al. (1996)</a> reported the cloning of cDNAs representing 3 unique human type 1 hexokinase mRNAs expressed in testis, which were not detected by Northern blot analysis in other human tissues. These mRNAs contained unique sequences in the 5-prime terminus and lacked the porin-binding domain (PBD), a conserved sequence that mediates the binding of hexokinase to the mitochondria. The sequences were similar to those identified by <a href="#16" class="mim-tip-reference" title="Mori, C., Welch, J. E., Fulcher, K. D., O'Brien, D. A., Eddy, E. M. <strong>Unique hexokinase messenger ribonucleic acids lacking the porin-binding domain are developmentally expressed in mouse spermatogenic cells.</strong> Biol. Reprod. 49: 191-203, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8396993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8396993</a>] [<a href="https://doi.org/10.1095/biolreprod49.2.191" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8396993">Mori et al. (1993)</a> in mouse testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8396993+8722688" 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="#1" class="mim-tip-reference" title="Amendola, C. R., Mahaffey, J. P., Parker, S. J., Ahearn, I. M., Chen, W.-C., Zhou, M., Court, H., Shi, J., Mendoza, S. L., Morten, M. J., Rothenberg, E., Gottlieb, E., Wadghiri, Y. Z., Possemato, R., Hubbard, S. R., Balmain, A., Kimmelman, A. C., Philips, M. R. <strong>KRAS4A directly regulates hexokinase 1.</strong> Nature 576: 482-486, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31827279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31827279</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31827279[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/10.1038/s41586-019-1832-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31827279">Amendola et al. (2019)</a> reported a direct, GTP-dependent interaction between the KRAS exon 4A-specific isoform KRAS4A (see <a href="/entry/190070">190070</a>) and HK1 that alters the activity of the kinase, and thereby established that HK1 is an effector of KRAS4A. This interaction is unique to KRAS4A because the palmitoylation-depalmitoylation cycle of this RAS isoform enables colocalization with HK1 on the outer mitochondrial membrane. The expression of KRAS4A in cancer may drive unique metabolic vulnerabilities that can be exploited therapeutically. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31827279" 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="#24" class="mim-tip-reference" title="Ruzzo, A., Andreoni, F., Magnani, M. <strong>Structure of the human hexokinase type I gene and nucleotide sequence of the 5-prime flanking region.</strong> Biochem. J. 331: 607-613, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9531504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9531504</a>] [<a href="https://doi.org/10.1042/bj3310607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9531504">Ruzzo et al. (1998)</a> determined that the HK1 gene contains 18 exons and spans about 75 kb. Analysis of the 5-prime flanking region revealed binding sites for AP1 and CRE as well as several binding sites for SP1. <a href="#24" class="mim-tip-reference" title="Ruzzo, A., Andreoni, F., Magnani, M. <strong>Structure of the human hexokinase type I gene and nucleotide sequence of the 5-prime flanking region.</strong> Biochem. J. 331: 607-613, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9531504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9531504</a>] [<a href="https://doi.org/10.1042/bj3310607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9531504">Ruzzo et al. (1998)</a> identified an exon 1 specific to HK1 expressed in somatic cells; an alternative exon (exon 1R) transcribed in red blood cells replaced the somatic exon 1 by alternative splicing. Exon 1R lacks the porin-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9531504" 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="Andreoni, F., Ruzzo, A., Magnani, M. <strong>Structure of the 5-prime region of the human hexokinase type I (HKI) gene and identification of an additional testis-specific HKI mRNA.</strong> Biochim. Biophys. Acta 1493: 19-26, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10978502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10978502</a>] [<a href="https://doi.org/10.1016/s0167-4781(00)00147-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10978502">Andreoni et al. (2000)</a> found that multiple testis-specific HK1 transcripts are encoded by 6 different exons; 5 of the exons are located upstream from the somatic exon 1, and one is located within intron 1. With identification of these additional exons, they determined that the gene spans at least 100 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10978502" 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="#28" class="mim-tip-reference" title="Shows, T. B. <strong>Synteny of human genes for glutamic oxaloacetic transaminase and hexokinase in somatic cell hybrids.</strong> Cytogenet. Cell Genet. 13: 143-145, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4827482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4827482</a>] [<a href="https://doi.org/10.1159/000130258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4827482">Shows (1974)</a> presented evidence from somatic cell hybrid experiments that hexokinase and cytoplasmic glutamate oxaloacetic transaminase are syntenic on chromosome 10. By gene dosage studies of fibroblasts, <a href="#11" class="mim-tip-reference" title="Gitelman, B. J., Simpson, N. E. <strong>Regional mapping of the locus for hexokinase-1 (HK1) to 10p11-q23 by gene dosage in human fibroblasts.</strong> Hum. Genet. 60: 227-229, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7106753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7106753</a>] [<a href="https://doi.org/10.1007/BF00303008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7106753">Gitelman and Simpson (1982)</a> mapped HK1 to 10p11-q23. By dosage effect, <a href="#7" class="mim-tip-reference" title="Dallapiccola, B., Lungarotti, M. S., Magnani, M., Dacha, M. <strong>Evidence of gene dosage effect for HK1 in the red cells of a patient with trisomy 10pter leads to p13.</strong> Ann. Genet. 24: 45-47, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6971618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6971618</a>]" pmid="6971618">Dallapiccola et al. (1981)</a> narrowed the HK1 assignment to 10pter-p13. <a href="#8" class="mim-tip-reference" title="Dallapiccola, B., Novelli, G., Micara, G., Delaroche, I., Moric-Petrovic, S., Magnani, M. <strong>Regional mapping of hexokinase-1 within the short arm of chromosome 10.</strong> Hum. Hered. 34: 156-160, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6590458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6590458</a>] [<a href="https://doi.org/10.1159/000153453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6590458">Dallapiccola et al. (1984)</a> determined HK1 activity in the red cells of 5 patients with various partial duplications of 10p and concluded that the most likely regional assignment for HK1 is 10p11.2. By in situ hybridization, <a href="#27" class="mim-tip-reference" title="Shows, T. B., Eddy, R. L., Byers, M. G., Haley, L. L., Henry, W. M., Nishi, S., Bell, G. I. <strong>Localization of the human hexokinase I gene (HK1) to chromosome 10q22. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1079 only, 1989."None>Shows et al. (1989)</a> regionalized the HK1 gene to 10q22. <a href="#9" class="mim-tip-reference" title="Daniele, A., Altruda, F., Ferrone, M., Silengo, L., Romeo, G., Archidiacono, N., Rocchi, M. <strong>Mapping of human hexokinase 1 gene to 10q11-qter.</strong> Hum. Hered. 42: 107-110, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1572668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1572668</a>] [<a href="https://doi.org/10.1159/000154049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1572668">Daniele et al. (1992)</a> used an HK1 cDNA as a probe for the study of a panel of human-hamster somatic cell hybrids to assign the gene to the long arm of chromosome 10 in the region q11.2-qter. This result agrees with those reported by <a href="#11" class="mim-tip-reference" title="Gitelman, B. J., Simpson, N. E. <strong>Regional mapping of the locus for hexokinase-1 (HK1) to 10p11-q23 by gene dosage in human fibroblasts.</strong> Hum. Genet. 60: 227-229, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7106753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7106753</a>] [<a href="https://doi.org/10.1007/BF00303008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7106753">Gitelman and Simpson (1982)</a> and <a href="#27" class="mim-tip-reference" title="Shows, T. B., Eddy, R. L., Byers, M. G., Haley, L. L., Henry, W. M., Nishi, S., Bell, G. I. <strong>Localization of the human hexokinase I gene (HK1) to chromosome 10q22. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1079 only, 1989."None>Shows et al. (1989)</a> but conflicts with that reported by <a href="#8" class="mim-tip-reference" title="Dallapiccola, B., Novelli, G., Micara, G., Delaroche, I., Moric-Petrovic, S., Magnani, M. <strong>Regional mapping of hexokinase-1 within the short arm of chromosome 10.</strong> Hum. Hered. 34: 156-160, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6590458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6590458</a>] [<a href="https://doi.org/10.1159/000153453" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6590458">Dallapiccola et al. (1984)</a>. <a href="#9" class="mim-tip-reference" title="Daniele, A., Altruda, F., Ferrone, M., Silengo, L., Romeo, G., Archidiacono, N., Rocchi, M. <strong>Mapping of human hexokinase 1 gene to 10q11-qter.</strong> Hum. Hered. 42: 107-110, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1572668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1572668</a>] [<a href="https://doi.org/10.1159/000154049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1572668">Daniele et al. (1992)</a> acknowledged the possibility that the HK1 probe they used recognized more than a single locus but concluded that if 2 or more HK loci exist they are all located on chromosome 10. <a href="#10" class="mim-tip-reference" title="Gelb, B. D., Worley, K. C., Griffin, L. D., Adams, V., Chinault, A. C., McCabe, E. R. B. <strong>Characterization of human genomic artificial chromosome inserts containing hexokinase 1 coding information on chromosome 10.</strong> Biochem. Med. Metab. Biol. 47: 265-269, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1627358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1627358</a>] [<a href="https://doi.org/10.1016/0885-4505(92)90035-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1627358">Gelb et al. (1992)</a> demonstrated that most of the coding region of the HK1 gene is located in a 120-kb YAC, which mapped entirely to chromosome 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4827482+1572668+6590458+6971618+1627358+7106753" 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 genes for 3 separate hexokinases have been assigned to specific sites as of 1997: HK1, a red-cell isoform, to chromosome 10; HK2 (<a href="/entry/601125">601125</a>), the major hexokinase expressed in skeletal muscle, to chromosome 2; and HK3 (<a href="/entry/142570">142570</a>), an isoform in white blood cells, to chromosome 5. Hexokinase-4 (HK4) is glucokinase (GCK; <a href="/entry/138079">138079</a>), which maps to chromosome 7.</p>
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<p><strong><em>Anemia, Congenital, Nonspherocytic Hemolytic, 5</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Bianchi, M., Magnani, M. <strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong> Blood Cells Mol. Dis. 21: 2-8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655856</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655856">Bianchi and Magnani (1995)</a> reported the molecular characterization of the defect in HK1 in a patient with hemolytic anemia due to hexokinase deficiency (CNSHA5; <a href="/entry/235700">235700</a>). PCR amplification and sequence of the cDNA revealed compound heterozygosity for a deletion and a single nucleotide substitution. The 96-bp deletion (<a href="#0001">142600.0001</a>) involved nucleotides 577 to 672 of their cDNA sequence and was found in the cDNA of none of 14 unrelated normal subjects. The sequence of the HK1 allele without deletion showed a T-to-C transition of nucleotide 1677, which caused the amino acid change leu529-to-ser (<a href="#0002">142600.0002</a>). The substitution was not found in 10 normal controls. <a href="#4" class="mim-tip-reference" title="Bianchi, M., Magnani, M. <strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong> Blood Cells Mol. Dis. 21: 2-8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655856</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655856">Bianchi and Magnani (1995)</a> stated that to their knowledge only 14 cases had been described, 2 of which had been studied in their laboratory: HK-Melzo and HK-Napoli. It was in HK-Melzo that the molecular defect was demonstrated. They showed that in the HK-Melzo variant, the HK deficiency was expressed not only in erythrocytes but also in platelets, lymphocytes, and fibroblasts. All these types of cells contain HK type I as the predominant glucose phosphorylating enzyme and, in particular, platelets and erythrocytes share a strict dependence upon glucose utilization for their physiologic functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7655856" 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 girl, born of consanguineous parents, with CNSHA5, who was previously reported by <a href="#21" class="mim-tip-reference" title="Rijksen, G., Akkerman, J. W. N., van den Wall Bake, A. W. L., Hofstede, D. P., Staal, G. E. J. <strong>Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia.</strong> Blood 61: 12-18, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6848140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6848140</a>]" pmid="6848140">Rijksen et al. (1983)</a>, <a href="#32" class="mim-tip-reference" title="van Wijk, R., Rijksen, G,, Huizinga, E. G., Nieuwenhuis, H. K., van Solinge, W. W. <strong>HK Utrecht: missense mutation in the active site of human hexokinase associated with hexokinase deficiency and severe nonspherocytic hemolytic anemia.</strong> Blood 101: 345-347, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393545</a>] [<a href="https://doi.org/10.1182/blood-2002-06-1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393545">van Wijk et al. (2003)</a> identified a homozygous mutation in the HK1 gene (T680S; <a href="#0004">142600.0004</a>). The mutation, which segregated with the disorder in the family and was not found in 50 controls, was designated 'Utrecht.' In vitro studies of the mutant enzyme showed that it had a 2-fold decrease in affinity for Mg-ATP2 and a markedly decreased affinity for the inhibitor glucose-1,6-diphosphate. Patient red cells and platelets had about 25% residual activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12393545+6848140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hereditary Motor and Sensory Neuropathy, Russe Type</em></strong></p><p>
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In all 34 European Gypsy individuals with the Russe type of hereditary motor and sensory neuropathy (HMSNR; <a href="/entry/605285">605285</a>) who were studied, <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a> identified a homozygous sequence change in the HK1 gene (<a href="#0003">142600.0003</a>) that mapped within the candidate disease interval on chromosome 10q. The mutation was located at a highly conserved nucleotide in the putative AltT2 exon located in the 5-prime region upstream of HK1. The variant was found in heterozygous state in 5 of 790 control individuals representing a cross-section of the Gypsy population, but not in 233 Bulgarian controls. AltT2-containing transcripts in the mouse peripheral nerve were rare compared to the coding region of HK1. However, 6 of 8 testis AltT2-containing isoforms were found, with expression patterns differing between the peripheral nerve and the brain and between newborn and adult tissues in mice. There was no difference in HK1 mRNA in Schwann cells derived from patients or controls, and patient cells showed no evidence of HK1 enzyme activity compared to controls. Bioinformatic tools did not suggest an effect of the variant on HK1 gene splicing or binding sites for interacting proteins. However, there was evidence that the variant may cause a ter-to-tyr substitution in 1 upstream open reading frame that had a non-AUG start codon, which could potentially disrupt HK1 translation regulation. <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a> speculated that non-OMM-binding HK1 may play a role in the pathogenesis of HMSNR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19536174" 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="#26" class="mim-tip-reference" title="Sevilla, T., Martinez-Rubio, D., Marquez, C., Paradas, C., Colomer, J., Jaijo, T., Millan, J. M., Palau, F., Espinos, C. <strong>Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.</strong> Clin. Genet. 83: 565-570, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978647</a>] [<a href="https://doi.org/10.1111/cge.12015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978647">Sevilla et al. (2013)</a> found that 11 patients from 9 Roma Gypsy families were homozygous for the HK1 variant (g.9712G-C; <a href="#0003">142600.0003</a>) identified by <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a>. Haplotype analysis confirmed a founder effect in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22978647+19536174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Retinitis Pigmentosa 79</em></strong></p><p>
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In affected individuals from 5 families (UTAD003, UTAD936, UTAD952, MOGL1, and MOGL2) segregating autosomal dominant retinitis pigmentosa (RP79; <a href="/entry/617460">617460</a>), <a href="#30" class="mim-tip-reference" title="Sullivan, L. S., Koboldt, D. C., Bowne, S. J., Lang, S., Blanton, S. H., Cadena, E., Avery, C. E., Lewis, R. A., Webb-Jones, K., Wheaton, D. H., Birch, D. G., Coussa, R., and 9 others. <strong>A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.</strong> Invest. Ophthal. Vis. Sci. 55: 7147-7158, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190649[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/10.1167/iovs.14-15419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25190649">Sullivan et al. (2014)</a> identified heterozygosity for a missense mutation in the HK1 gene (E847K; <a href="#0005">142600.0005</a>) that segregated fully with disease in each family and was not found in public variant databases. None of the patients had extraocular manifestations and no systemic abnormalities in glycolysis were detected, even in 1 patient who was homozygous for the mutation. <a href="#30" class="mim-tip-reference" title="Sullivan, L. S., Koboldt, D. C., Bowne, S. J., Lang, S., Blanton, S. H., Cadena, E., Avery, C. E., Lewis, R. A., Webb-Jones, K., Wheaton, D. H., Birch, D. G., Coussa, R., and 9 others. <strong>A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.</strong> Invest. Ophthal. Vis. Sci. 55: 7147-7158, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190649[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/10.1167/iovs.14-15419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25190649">Sullivan et al. (2014)</a> noted that the mutation is located outside the catalytic domains and suggested that the effect of the mutation was limited to the retina. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25190649" 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 affected individuals from a large 4-generation family of northern European ancestry with RP, <a href="#33" class="mim-tip-reference" title="Wang, F., Wang, Y., Zhang, B., Zhao, L., Lyubasyuk, V., Wang, K., Xu, M., Li, Y., Wu, F., Wen, C., Bernstein, P. S., Lin, D., Zhu, S., Wang, H., Zhang, K., Chen, R. <strong>A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa.</strong> Invest. Ophthal. Vis. Sci. 55: 7159-4164, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25316723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25316723</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25316723[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/10.1167/iovs.14-15520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25316723">Wang et al. (2014)</a> identified heterozygosity for the E847K mutation in the HK1 gene. Affected individuals showed no signs of anemia, exercise intolerance, or cognitive defects. Biochemical assays revealed no obvious differences between the mutant and wildtype alleles in terms of enzymatic activity or mRNA and protein expression levels, suggesting that hexokinase deficiency is not likely to be the underlying mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25316723" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neurodevelopmental Disorder with Visual Defects and Brain Anomalies</em></strong></p><p>
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In 7 patients from 6 unrelated families with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; <a href="/entry/618547">618547</a>), <a href="#20" class="mim-tip-reference" title="Okur, V., Cho, M. T., van Wijk, R., van Oirschot, B., Picker, J., Coury, S. A., Grange, D., Manwaring, L., Krantz, I., Muraresku, C. C., Hulick, P. J., May, H., and 11 others. <strong>De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.</strong> Europ. J. Hum. Genet. 27: 1081-1089, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30778173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30778173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30778173[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/10.1038/s41431-019-0366-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30778173">Okur et al. (2019)</a> identified 4 different de novo heterozygous missense mutations in the HK1 gene (<a href="#0006">142600.0006</a>-<a href="#0009">142600.0009</a>). All mutations occurred at highly conserved residues in the N-terminal regulatory domain. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Blood cells from 2 unrelated patients had normal hexokinase activity, suggesting a different pathogenic mechanism. Other functional studies of the variant and studies of patient cells were not performed, but the authors postulated a gain-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30778173" 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="#25" class="mim-tip-reference" title="Schimke, R. T., Grossbard, L. <strong>Studies on isozymes of hexokinase in animal tissues.</strong> Ann. N.Y. Acad. Sci. 151: 332-350, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4975693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4975693</a>] [<a href="https://doi.org/10.1111/j.1749-6632.1968.tb11899.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4975693">Schimke and Grossbard (1968)</a> reviewed studies of hexokinase isozymes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4975693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with nonspherocytic hemolytic anemia with the so-called HK-Melzo variant of hexokinase deficiency (CNSHA5; <a href="/entry/235700">235700</a>), <a href="#4" class="mim-tip-reference" title="Bianchi, M., Magnani, M. <strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong> Blood Cells Mol. Dis. 21: 2-8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655856</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655856">Bianchi and Magnani (1995)</a> demonstrated compound heterozygosity for mutations in the HK1 gene: a 96-bp deletion of nucleotides 577 to 672 and a 1667T-C transition, resulting in a leu529-to-ser substitution (<a href="#0002">142600.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7655856" 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>For discussion of the leu529-to-ser (L529S) mutation in the HK1 gene that was found in compound heterozygous state in a patient with nonspherocytic hemolytic anemia due to hexokinase deficiency (CNSHA5; <a href="/entry/235700">235700</a>) by <a href="#4" class="mim-tip-reference" title="Bianchi, M., Magnani, M. <strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong> Blood Cells Mol. Dis. 21: 2-8, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655856</a>] [<a href="https://doi.org/10.1006/bcmd.1995.0002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7655856">Bianchi and Magnani (1995)</a>, see <a href="#0001">142600.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7655856" 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">rs397514654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514654;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=rs397514654" 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=rs397514654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In all 34 individuals with the Russe type of hereditary motor and sensory neuropathy (HMSNR; <a href="/entry/605285">605285</a>) who were studied, <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a> identified 2 homozygous sequence changes in the HK1 gene, which maps within the candidate disease interval on chromosome 10q. One was a G-to-C transversion at a highly conserved nucleotide in the putative AltT2 exon located in the 5-prime region upstream of HK1 (-3818-195G-C, NM_033497; <a href="#5" class="mim-tip-reference" title="Chandler, D. <strong>Personal Communication.</strong> Perth, Australia 3/16/2013."None>Chandler, 2013</a>), and the other was an intronic G-to-A transition downstream of the AltT2 change; the G-to-A transition was not highly conserved, and thus not thought to be pathogenic. These 2 variants were found in heterozygous state in 5 of 790 control individuals representing a cross-section of the Gypsy population, but not in 233 Bulgarian controls. AltT2-containing transcripts in the mouse peripheral nerve were rare compared to the coding region of HK1. However, 6 of 8 testis AltT2-containing isoforms were found, with expression patterns differing between the peripheral nerve and the brain and between newborn and adult tissues in mice. There was no difference in HK1 mRNA in Schwann cells derived from patients or controls, and patient cells showed no evidence of HK1 enzyme activity compared to controls. Bioinformatic tools did not suggest an effect of the G-C change on HK1 gene splicing or binding sites for interacting proteins. However, there was evidence that the G-C change may cause a ter-to-tyr substitution in 1 upstream open reading frame that had a non-AUG start codon, which could potentially disrupt HK1 translation regulation. <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a> speculated that non-OMM-binding HK1 may play a role in the pathogenesis of HMSNR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19536174" 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="#26" class="mim-tip-reference" title="Sevilla, T., Martinez-Rubio, D., Marquez, C., Paradas, C., Colomer, J., Jaijo, T., Millan, J. M., Palau, F., Espinos, C. <strong>Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.</strong> Clin. Genet. 83: 565-570, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978647</a>] [<a href="https://doi.org/10.1111/cge.12015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22978647">Sevilla et al. (2013)</a> found that 11 patients from 9 Roma Gypsy families with progressive hereditary motor and sensory neuropathy were homozygous for the HK1 variant (g.9712G-C) identified by <a href="#14" class="mim-tip-reference" title="Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L. <strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong> Europ. J. Hum. Genet. 17: 1606-1614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19536174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19536174</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19536174[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/10.1038/ejhg.2009.99" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19536174">Hantke et al. (2009)</a>, and haplotype analysis confirmed a founder effect in this population. The founding ancestor was estimated to have lived at the end of the 18th century, when a population split occurred from a tribal group and the Gypsy population in Spain increased under the rule of Charles III. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22978647+19536174" 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>.0004 ANEMIA, CONGENITAL, NONSPHEROCYTIC HEMOLYTIC, 5</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs398122379 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122379;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/rs398122379?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=rs398122379" 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=rs398122379" 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=RCV000049268" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049268" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049268</a>
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<p>In a girl, born of consanguineous parents, with severe nonspherocytic hemolytic anemia due to hexokinase deficiency (CNSHA5; <a href="/entry/235700">235700</a>), who was previously reported by <a href="#21" class="mim-tip-reference" title="Rijksen, G., Akkerman, J. W. N., van den Wall Bake, A. W. L., Hofstede, D. P., Staal, G. E. J. <strong>Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia.</strong> Blood 61: 12-18, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6848140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6848140</a>]" pmid="6848140">Rijksen et al. (1983)</a>, <a href="#32" class="mim-tip-reference" title="van Wijk, R., Rijksen, G,, Huizinga, E. G., Nieuwenhuis, H. K., van Solinge, W. W. <strong>HK Utrecht: missense mutation in the active site of human hexokinase associated with hexokinase deficiency and severe nonspherocytic hemolytic anemia.</strong> Blood 101: 345-347, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393545</a>] [<a href="https://doi.org/10.1182/blood-2002-06-1851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393545">van Wijk et al. (2003)</a> identified a homozygous c.2039C-G transversion in exon 15 of the HK1 gene, resulting in a thr680-to-ser (T680S) substitution at a highly conserved residue in the active site. The mutation, which segregated with the disorder in the family and was not found in 50 controls, was designated 'Utrecht.' In vitro studies of the mutant enzyme showed that it had a 2-fold decrease in affinity for Mg-ATP2 and a markedly decreased affinity for the inhibitor glucose-1,6-diphosphate. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12393545+6848140" 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> rs777849213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs777849213;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/rs777849213?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=rs777849213" 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=rs777849213" 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=RCV000487470 OR RCV001064496 OR RCV001075827 OR RCV004584389 OR RCV004740261" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000487470, RCV001064496, RCV001075827, RCV004584389, RCV004740261" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000487470...</a>
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<p>In affected individuals from 5 families (UTAD003, UTAD936, UTAD952, MOGL1, and MOGL2) segregating autosomal dominant retinitis pigmentosa (RP79; <a href="/entry/617460">617460</a>), <a href="#30" class="mim-tip-reference" title="Sullivan, L. S., Koboldt, D. C., Bowne, S. J., Lang, S., Blanton, S. H., Cadena, E., Avery, C. E., Lewis, R. A., Webb-Jones, K., Wheaton, D. H., Birch, D. G., Coussa, R., and 9 others. <strong>A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.</strong> Invest. Ophthal. Vis. Sci. 55: 7147-7158, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190649[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/10.1167/iovs.14-15419" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25190649">Sullivan et al. (2014)</a> identified heterozygosity for a c.2539G-A transition (c.2539G-A, NM_000188.2) in the HK1 gene, resulting in a glu847-to-lys (E847K) substitution at a highly conserved residue outside of known functional domains. The mutation segregated fully with disease in all families and was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Haplotype analysis in the 5 families, 3 of which were from the Acadian population in Louisiana, 1 French Canadian, and 1 Sicilian, demonstrated a shared 450-kb region on chromosome 10, suggesting a founder mutation. One patient in family UTAD003, who was homozygous for the mutation, was diagnosed at age 4 years due to profound nyctalopia; examination at age 33 showed visual acuity reduced to counting fingers in the right eye and 20/200 in the left eye, and he exhibited the classic features of RP on funduscopy, with severe retinal vascular attenuation, diffuse optic disc pallor, extensive and broadly distributed pigment epithelial atrophy with bone spicule accumulation throughout the fundus, and macular atrophy in both eyes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25190649" 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 affected individuals from a large 4-generation family of European ancestry with RP, <a href="#33" class="mim-tip-reference" title="Wang, F., Wang, Y., Zhang, B., Zhao, L., Lyubasyuk, V., Wang, K., Xu, M., Li, Y., Wu, F., Wen, C., Bernstein, P. S., Lin, D., Zhu, S., Wang, H., Zhang, K., Chen, R. <strong>A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa.</strong> Invest. Ophthal. Vis. Sci. 55: 7159-4164, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25316723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25316723</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25316723[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/10.1167/iovs.14-15520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25316723">Wang et al. (2014)</a> identified heterozygosity for the E847K mutation in the HK1 gene, which segregated with disease in the family with 85% penetrance and was not found in 11,000 in-house exomes. Two asymptomatic family members who also carried the mutation exhibited unaffected vision and no bone-spicule pigmentation at ages 37 and 78 years, respectively. Affected individuals showed no signs of anemia, exercise intolerance, or cognitive defects. Functional analysis in HEK293T cells showed that mutant hexokinase activity as well as mRNA and protein levels were similar to those of the wildtype protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25316723" 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>.0006 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1064795154 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1064795154;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=rs1064795154" 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=rs1064795154" 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=RCV000487002 OR RCV000850126" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000487002, RCV000850126" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000487002...</a>
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<p>In a 34-year-old woman (patient 1) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; <a href="/entry/618547">618547</a>), <a href="#20" class="mim-tip-reference" title="Okur, V., Cho, M. T., van Wijk, R., van Oirschot, B., Picker, J., Coury, S. A., Grange, D., Manwaring, L., Krantz, I., Muraresku, C. C., Hulick, P. J., May, H., and 11 others. <strong>De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.</strong> Europ. J. Hum. Genet. 27: 1081-1089, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30778173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30778173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30778173[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/10.1038/s41431-019-0366-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30778173">Okur et al. (2019)</a> identified a de novo heterozygous c.1241G-A transition (c.1241G-A, NM_000188.2) in the HK1 gene, resulting in a gly414-to-glu (G414E) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30778173" 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">rs1564557037 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1564557037;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=rs1564557037" 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=rs1564557037" 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=RCV000782118 OR RCV000850127 OR RCV001805835" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000782118, RCV000850127, RCV001805835" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000782118...</a>
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<p>In a 9-year-old girl (patient 2) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; <a href="/entry/618547">618547</a>), <a href="#20" class="mim-tip-reference" title="Okur, V., Cho, M. T., van Wijk, R., van Oirschot, B., Picker, J., Coury, S. A., Grange, D., Manwaring, L., Krantz, I., Muraresku, C. C., Hulick, P. J., May, H., and 11 others. <strong>De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.</strong> Europ. J. Hum. Genet. 27: 1081-1089, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30778173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30778173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30778173[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/10.1038/s41431-019-0366-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30778173">Okur et al. (2019)</a> identified a de novo heterozygous c.1252A-G transition (c.1252A-G, NM_000188.2) in the HK1 gene, resulting in a lys418-to-glu (K418E) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Hexokinase activity in patient red cells was normal, suggesting a different pathogenic mechanism. Additional functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30778173" 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>.0008 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
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HK1, SER445LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1064794848 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1064794848;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=rs1064794848" 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=rs1064794848" 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=RCV000483739 OR RCV000850128 OR RCV001254702 OR RCV001266687 OR RCV001270352 OR RCV001770372 OR RCV003126749 OR RCV004816693" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000483739, RCV000850128, RCV001254702, RCV001266687, RCV001270352, RCV001770372, RCV003126749, RCV004816693" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000483739...</a>
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<p>In 2 unrelated patients (patients 3 and 4) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; <a href="/entry/618547">618547</a>), <a href="#20" class="mim-tip-reference" title="Okur, V., Cho, M. T., van Wijk, R., van Oirschot, B., Picker, J., Coury, S. A., Grange, D., Manwaring, L., Krantz, I., Muraresku, C. C., Hulick, P. J., May, H., and 11 others. <strong>De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.</strong> Europ. J. Hum. Genet. 27: 1081-1089, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30778173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30778173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30778173[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/10.1038/s41431-019-0366-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30778173">Okur et al. (2019)</a> identified a de novo heterozygous c.1334C-T transition (c.1334C-T, NM_000188.2) in the HK1 gene, resulting in a ser445-to-leu (S445L) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Hexokinase activity in patient red cells derived from 1 of the patients was normal, suggesting a different pathogenic mechanism. Additional functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30778173" 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>.0009 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057517928 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057517928;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=rs1057517928" 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=rs1057517928" 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=RCV000413860 OR RCV000763213 OR RCV000850129 OR RCV001266327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000413860, RCV000763213, RCV000850129, RCV001266327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000413860...</a>
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<p>In an 8-year-old boy (patient 5) and 2 sibs who died at 1 year of age (patients 6 and 7), with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; <a href="/entry/618547">618547</a>), <a href="#20" class="mim-tip-reference" title="Okur, V., Cho, M. T., van Wijk, R., van Oirschot, B., Picker, J., Coury, S. A., Grange, D., Manwaring, L., Krantz, I., Muraresku, C. C., Hulick, P. J., May, H., and 11 others. <strong>De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment.</strong> Europ. J. Hum. Genet. 27: 1081-1089, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30778173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30778173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30778173[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/10.1038/s41431-019-0366-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30778173">Okur et al. (2019)</a> identified a de novo heterozygous c.1370C-T transition (c.1370C-T, NM000188.2) in the HK1 gene, resulting in a thr457-to-met (T457M) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. The mutation occurred de novo in patient 5; paternal mosaicism in the blood was excluded in the sibs. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30778173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Chern1976" class="mim-tip-reference" title="Chern, C. J. <strong>Localization of the structural genes for hexokinase-1 and inorganic pyrophosphatase on region (pter-q24) of human chromosome 10.</strong> Cytogenet. Cell Genet. 17: 338-342, 1976.">Chern (1976)</a>; <a href="#Gitelman1980" class="mim-tip-reference" title="Gitelman, B. J., Tomkins, D. J., Partington, M. W., Roberts, M. H., Simpson, N. E. <strong>Gene dosage studies of glutamic oxaloacetic transaminase (GOT) and hexokinase (HK) in two patients with possible partial trisomy 10q. (Abstract)</strong> Am. J. Hum. Genet. 32: 41A only, 1980.">Gitelman et al. (1980)</a>; <a href="#Ritter1974" class="mim-tip-reference" title="Ritter, H., Friedrichson, U., Schmitt, J. <strong>Genetic polymorphism of hexokinase in primates.</strong> Humangenetik 22: 265-266, 1974.">Ritter et al. (1974)</a>; <a href="#Rogers1975" class="mim-tip-reference" title="Rogers, P. A., Fisher, R. A., Harris, H. <strong>An electrophoretic study of the distribution and properties of human hexokinases.</strong> Biochem. Genet. 13: 857-866, 1975.">Rogers et
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al. (1975)</a>; <a href="#Snyder1984" class="mim-tip-reference" title="Snyder, F. F., Lin, C. C., Rudd, N. L., Shearer, J. E., Heikkila, E. M., Hoo, J. J. <strong>A de novo case of trisomy 10p: gene dosage studies of hexokinase, inorganic pyrophosphatase and adenosine kinase.</strong> Hum. Genet. 67: 187-189, 1984.">Snyder et al. (1984)</a>
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Amendola, C. R., Mahaffey, J. P., Parker, S. J., Ahearn, I. M., Chen, W.-C., Zhou, M., Court, H., Shi, J., Mendoza, S. L., Morten, M. J., Rothenberg, E., Gottlieb, E., Wadghiri, Y. Z., Possemato, R., Hubbard, S. R., Balmain, A., Kimmelman, A. C., Philips, M. R.
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<strong>KRAS4A directly regulates hexokinase 1.</strong>
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Nature 576: 482-486, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31827279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31827279</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31827279[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=31827279" 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/s41586-019-1832-9" target="_blank">Full Text</a>]
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Andreoni, F., Ruzzo, A., Magnani, M.
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<strong>Structure of the 5-prime region of the human hexokinase type I (HKI) gene and identification of an additional testis-specific HKI mRNA.</strong>
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Biochim. Biophys. Acta 1493: 19-26, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10978502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10978502</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10978502" 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/s0167-4781(00)00147-0" target="_blank">Full Text</a>]
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Bianchi, M., Crinelli, R., Serafini, G. Giammarini, C., Magnani, M.
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<strong>Molecular bases of hexokinase deficiency.</strong>
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Biochim. Biophys. Acta 1360: 211-221, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9197463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9197463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9197463" 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/s0925-4439(96)00080-4" target="_blank">Full Text</a>]
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Bianchi, M., Magnani, M.
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<strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong>
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Blood Cells Mol. Dis. 21: 2-8, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7655856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7655856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7655856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/bcmd.1995.0002" target="_blank">Full Text</a>]
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Chandler, D.
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<strong>Personal Communication.</strong>
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Perth, Australia 3/16/2013.
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[<a href="https://doi.org/10.1159/000130736" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000153453" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000154049" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0885-4505(92)90035-w" target="_blank">Full Text</a>]
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<strong>Regional mapping of the locus for hexokinase-1 (HK1) to 10p11-q23 by gene dosage in human fibroblasts.</strong>
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[<a href="https://doi.org/10.1007/BF00303008" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0888-7543(91)90027-c" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ejhg.2009.99" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-2795(199605)44:1<14::AID-MRD2>3.0.CO;2-W" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1095/biolreprod49.2.191" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0006-291x(88)80964-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00484416" target="_blank">Full Text</a>]
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<strong>Structure of the human hexokinase type I gene and nucleotide sequence of the 5-prime flanking region.</strong>
|
|
Biochem. J. 331: 607-613, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9531504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9531504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9531504" 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/10.1042/bj3310607" target="_blank">Full Text</a>]
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</p>
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</div>
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<a id="25" class="mim-anchor"></a>
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<a id="Schimke1968" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schimke, R. T., Grossbard, L.
|
|
<strong>Studies on isozymes of hexokinase in animal tissues.</strong>
|
|
Ann. N.Y. Acad. Sci. 151: 332-350, 1968.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4975693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4975693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4975693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1749-6632.1968.tb11899.x" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="26" class="mim-anchor"></a>
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<a id="Sevilla2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sevilla, T., Martinez-Rubio, D., Marquez, C., Paradas, C., Colomer, J., Jaijo, T., Millan, J. M., Palau, F., Espinos, C.
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<strong>Genetics of the Charcot-Marie-Tooth disease in the Spanish Gypsy population: the hereditary motor and sensory neuropathy-Russe in depth.</strong>
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Clin. Genet. 83: 565-570, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22978647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22978647</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22978647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.12015" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="27" class="mim-anchor"></a>
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<a id="Shows1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shows, T. B., Eddy, R. L., Byers, M. G., Haley, L. L., Henry, W. M., Nishi, S., Bell, G. I.
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<strong>Localization of the human hexokinase I gene (HK1) to chromosome 10q22. (Abstract)</strong>
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Cytogenet. Cell Genet. 51: 1079 only, 1989.
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</p>
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<a id="28" class="mim-anchor"></a>
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<a id="Shows1974" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Shows, T. B.
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<strong>Synteny of human genes for glutamic oxaloacetic transaminase and hexokinase in somatic cell hybrids.</strong>
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Cytogenet. Cell Genet. 13: 143-145, 1974.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4827482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4827482</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4827482" 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/10.1159/000130258" target="_blank">Full Text</a>]
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<a id="29" class="mim-anchor"></a>
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<a id="Snyder1984" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Snyder, F. F., Lin, C. C., Rudd, N. L., Shearer, J. E., Heikkila, E. M., Hoo, J. J.
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<strong>A de novo case of trisomy 10p: gene dosage studies of hexokinase, inorganic pyrophosphatase and adenosine kinase.</strong>
|
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Hum. Genet. 67: 187-189, 1984.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6146563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6146563</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6146563" 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/10.1007/BF00272998" target="_blank">Full Text</a>]
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<a id="30" class="mim-anchor"></a>
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<a id="Sullivan2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sullivan, L. S., Koboldt, D. C., Bowne, S. J., Lang, S., Blanton, S. H., Cadena, E., Avery, C. E., Lewis, R. A., Webb-Jones, K., Wheaton, D. H., Birch, D. G., Coussa, R., and 9 others.
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<strong>A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.</strong>
|
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Invest. Ophthal. Vis. Sci. 55: 7147-7158, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190649[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=25190649" 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/10.1167/iovs.14-15419" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="31" class="mim-anchor"></a>
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<a id="Ureta1982" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ureta, T.
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<strong>The comparative isozymology of vertebrate hexokinases.</strong>
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Comp. Biochem. Physiol. B 71: 549-555, 1982.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7044667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7044667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7044667" 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/10.1016/0305-0491(82)90461-8" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="32" class="mim-anchor"></a>
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<a id="van Wijk2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Wijk, R., Rijksen, G,, Huizinga, E. G., Nieuwenhuis, H. K., van Solinge, W. W.
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<strong>HK Utrecht: missense mutation in the active site of human hexokinase associated with hexokinase deficiency and severe nonspherocytic hemolytic anemia.</strong>
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Blood 101: 345-347, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood-2002-06-1851" target="_blank">Full Text</a>]
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<li>
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<a id="33" class="mim-anchor"></a>
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<a id="Wang2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, F., Wang, Y., Zhang, B., Zhao, L., Lyubasyuk, V., Wang, K., Xu, M., Li, Y., Wu, F., Wen, C., Bernstein, P. S., Lin, D., Zhu, S., Wang, H., Zhang, K., Chen, R.
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<strong>A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa.</strong>
|
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Invest. Ophthal. Vis. Sci. 55: 7159-4164, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25316723/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25316723</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25316723[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=25316723" 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/10.1167/iovs.14-15520" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 05/13/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/20/2019<br>Marla J. F. O'Neill - updated : 04/27/2017<br>Cassandra L. Kniffin - updated : 7/9/2013<br>Cassandra L. Kniffin - updated : 6/4/2013<br>Cassandra L. Kniffin - updated : 3/5/2013<br>Patricia A. Hartz - updated : 8/5/2002<br>Victor A. McKusick - updated : 4/4/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 10/11/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 05/13/2020<br>carol : 08/22/2019<br>carol : 08/21/2019<br>ckniffin : 08/20/2019<br>carol : 04/27/2017<br>tpirozzi : 07/09/2013<br>ckniffin : 7/9/2013<br>carol : 7/8/2013<br>carol : 6/7/2013<br>ckniffin : 6/4/2013<br>carol : 3/18/2013<br>carol : 3/8/2013<br>ckniffin : 3/5/2013<br>carol : 7/7/2010<br>carol : 8/5/2002<br>dkim : 7/2/1998<br>jenny : 4/4/1997<br>terry : 4/1/1997<br>mark : 11/6/1996<br>mark : 11/1/1995<br>davew : 8/5/1994<br>carol : 11/20/1992<br>carol : 10/13/1992<br>carol : 8/31/1992<br>carol : 8/21/1992
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 142600
|
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</span>
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</h3>
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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HEXOKINASE 1; HK1
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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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<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: HK1</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>SNOMEDCT:</strong> 715799004;
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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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<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: 10q22.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:69,270,000-69,401,882 </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">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
|
|
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>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
|
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</thead>
|
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<tbody>
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|
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<tr>
|
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<td rowspan="4">
|
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<span class="mim-font">
|
|
10q22.1
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Anemia, congenital, nonspherocytic hemolytic, 5, hexokinase deficient
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
235700
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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Neurodevelopmental disorder with visual defects and brain anomalies
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</span>
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</td>
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<td>
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<span class="mim-font">
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618547
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Neuropathy, hereditary motor and sensory, Russe type
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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605285
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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Retinitis pigmentosa 79
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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617460
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hexokinase (EC 2.7.1.1) catalyzes the first step in glucose metabolism, using ATP for the phosphorylation of glucose to glucose-6-phosphate. Four different forms of hexokinase, designated type HK1, HK2 (601125), HK3 (142570), and HK4 (138079), encoded by different genes, are present in mammalian tissues. Among these, HK1 is the predominant glucose phosphorylating activity in those tissues that share a strict dependence on glucose utilization for their physiologic functions, such as brain, erythrocytes, platelets, lymphocytes, and fibroblasts (summary by Bianchi et al., 1997). Different isoforms of HK1 are either cytoplasmic or associated with the outer mitochondrial membrane (OMM) through a 5-prime porin (VDAC1; 604492)-binding domain (Murakami and Piomelli, 1997). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nishi et al. (1988) analyzed cDNA clones encoding human hexokinase isolated from an adult kidney library. Analysis of this 917-amino acid protein showed that the sequences of the N- and C-terminal halves, corresponding to the regulatory and catalytic domains, respectively, are homologous. Eukaryotic hexokinases evolved from duplication of a gene encoding a protein of about 450 amino acids. Griffin et al. (1991) thought that comparisons of sequences in many species supported the theory of Ureta (1982) that the mammalian hexokinases arose from the duplication and fusion of an ancestral protoenzyme and that the yeast and mammalian glucokinases arose twice in evolution. Sequence analysis demonstrated that a 15-amino acid porin-binding domain in the N terminus of HK1 is absolutely conserved and mediates the binding of HK1 to the mitochondria. In the course of their work, Griffin et al. (1991) developed a method for cloning the cDNA for a low abundance protein using knowledge of the evolutionary conservation of amino acid and nucleotide sequence. </p><p>By liquid chromatography, Murakami et al. (1990) identified 2 distinct major isozymes of human red blood cell (RBC) hexokinase. One had a molecular mass similar to that of HK1 identified in liver, and the other, designated HKR, was larger than HK1 by several kilodaltons. RBC from normal blood contained HK1 and HKR at an equal activity, but in reticulocyte-rich RBC, HKR dominated. Murakami and Piomelli (1997) isolated a cDNA clone for the red cell-specific HK isozyme HKR. Its nucleotide sequence was identical to HK1 cDNA except for the 5-prime end. It lacks the first 62 nucleotides of the HK1 coding region; instead, it contains a unique sequence of 60 nucleotides at the beginning of the coding sequence as well as another unique sequence upstream of the putative translation initiation site. It lacks the porin-binding domain that facilitates binding to mitochondria, thus explaining the exclusive cytoplasmic localization of red blood cell HK. Northern blot analysis showed that it was expressed in reticulocytes and in an erythroleukemic cell line, but not in a lymphocytic cell line. </p><p>Mori et al. (1996) reported the cloning of cDNAs representing 3 unique human type 1 hexokinase mRNAs expressed in testis, which were not detected by Northern blot analysis in other human tissues. These mRNAs contained unique sequences in the 5-prime terminus and lacked the porin-binding domain (PBD), a conserved sequence that mediates the binding of hexokinase to the mitochondria. The sequences were similar to those identified by Mori et al. (1993) in mouse testis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Amendola et al. (2019) reported a direct, GTP-dependent interaction between the KRAS exon 4A-specific isoform KRAS4A (see 190070) and HK1 that alters the activity of the kinase, and thereby established that HK1 is an effector of KRAS4A. This interaction is unique to KRAS4A because the palmitoylation-depalmitoylation cycle of this RAS isoform enables colocalization with HK1 on the outer mitochondrial membrane. The expression of KRAS4A in cancer may drive unique metabolic vulnerabilities that can be exploited therapeutically. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ruzzo et al. (1998) determined that the HK1 gene contains 18 exons and spans about 75 kb. Analysis of the 5-prime flanking region revealed binding sites for AP1 and CRE as well as several binding sites for SP1. Ruzzo et al. (1998) identified an exon 1 specific to HK1 expressed in somatic cells; an alternative exon (exon 1R) transcribed in red blood cells replaced the somatic exon 1 by alternative splicing. Exon 1R lacks the porin-binding domain. </p><p>Andreoni et al. (2000) found that multiple testis-specific HK1 transcripts are encoded by 6 different exons; 5 of the exons are located upstream from the somatic exon 1, and one is located within intron 1. With identification of these additional exons, they determined that the gene spans at least 100 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Shows (1974) presented evidence from somatic cell hybrid experiments that hexokinase and cytoplasmic glutamate oxaloacetic transaminase are syntenic on chromosome 10. By gene dosage studies of fibroblasts, Gitelman and Simpson (1982) mapped HK1 to 10p11-q23. By dosage effect, Dallapiccola et al. (1981) narrowed the HK1 assignment to 10pter-p13. Dallapiccola et al. (1984) determined HK1 activity in the red cells of 5 patients with various partial duplications of 10p and concluded that the most likely regional assignment for HK1 is 10p11.2. By in situ hybridization, Shows et al. (1989) regionalized the HK1 gene to 10q22. Daniele et al. (1992) used an HK1 cDNA as a probe for the study of a panel of human-hamster somatic cell hybrids to assign the gene to the long arm of chromosome 10 in the region q11.2-qter. This result agrees with those reported by Gitelman and Simpson (1982) and Shows et al. (1989) but conflicts with that reported by Dallapiccola et al. (1984). Daniele et al. (1992) acknowledged the possibility that the HK1 probe they used recognized more than a single locus but concluded that if 2 or more HK loci exist they are all located on chromosome 10. Gelb et al. (1992) demonstrated that most of the coding region of the HK1 gene is located in a 120-kb YAC, which mapped entirely to chromosome 10. </p><p>The genes for 3 separate hexokinases have been assigned to specific sites as of 1997: HK1, a red-cell isoform, to chromosome 10; HK2 (601125), the major hexokinase expressed in skeletal muscle, to chromosome 2; and HK3 (142570), an isoform in white blood cells, to chromosome 5. Hexokinase-4 (HK4) is glucokinase (GCK; 138079), which maps to chromosome 7.</p>
|
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</span>
|
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<div>
|
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<br />
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p><strong><em>Anemia, Congenital, Nonspherocytic Hemolytic, 5</em></strong></p><p>
|
|
Bianchi and Magnani (1995) reported the molecular characterization of the defect in HK1 in a patient with hemolytic anemia due to hexokinase deficiency (CNSHA5; 235700). PCR amplification and sequence of the cDNA revealed compound heterozygosity for a deletion and a single nucleotide substitution. The 96-bp deletion (142600.0001) involved nucleotides 577 to 672 of their cDNA sequence and was found in the cDNA of none of 14 unrelated normal subjects. The sequence of the HK1 allele without deletion showed a T-to-C transition of nucleotide 1677, which caused the amino acid change leu529-to-ser (142600.0002). The substitution was not found in 10 normal controls. Bianchi and Magnani (1995) stated that to their knowledge only 14 cases had been described, 2 of which had been studied in their laboratory: HK-Melzo and HK-Napoli. It was in HK-Melzo that the molecular defect was demonstrated. They showed that in the HK-Melzo variant, the HK deficiency was expressed not only in erythrocytes but also in platelets, lymphocytes, and fibroblasts. All these types of cells contain HK type I as the predominant glucose phosphorylating enzyme and, in particular, platelets and erythrocytes share a strict dependence upon glucose utilization for their physiologic functions. </p><p>In a girl, born of consanguineous parents, with CNSHA5, who was previously reported by Rijksen et al. (1983), van Wijk et al. (2003) identified a homozygous mutation in the HK1 gene (T680S; 142600.0004). The mutation, which segregated with the disorder in the family and was not found in 50 controls, was designated 'Utrecht.' In vitro studies of the mutant enzyme showed that it had a 2-fold decrease in affinity for Mg-ATP2 and a markedly decreased affinity for the inhibitor glucose-1,6-diphosphate. Patient red cells and platelets had about 25% residual activity. </p><p><strong><em>Hereditary Motor and Sensory Neuropathy, Russe Type</em></strong></p><p>
|
|
In all 34 European Gypsy individuals with the Russe type of hereditary motor and sensory neuropathy (HMSNR; 605285) who were studied, Hantke et al. (2009) identified a homozygous sequence change in the HK1 gene (142600.0003) that mapped within the candidate disease interval on chromosome 10q. The mutation was located at a highly conserved nucleotide in the putative AltT2 exon located in the 5-prime region upstream of HK1. The variant was found in heterozygous state in 5 of 790 control individuals representing a cross-section of the Gypsy population, but not in 233 Bulgarian controls. AltT2-containing transcripts in the mouse peripheral nerve were rare compared to the coding region of HK1. However, 6 of 8 testis AltT2-containing isoforms were found, with expression patterns differing between the peripheral nerve and the brain and between newborn and adult tissues in mice. There was no difference in HK1 mRNA in Schwann cells derived from patients or controls, and patient cells showed no evidence of HK1 enzyme activity compared to controls. Bioinformatic tools did not suggest an effect of the variant on HK1 gene splicing or binding sites for interacting proteins. However, there was evidence that the variant may cause a ter-to-tyr substitution in 1 upstream open reading frame that had a non-AUG start codon, which could potentially disrupt HK1 translation regulation. Hantke et al. (2009) speculated that non-OMM-binding HK1 may play a role in the pathogenesis of HMSNR. </p><p>Sevilla et al. (2013) found that 11 patients from 9 Roma Gypsy families were homozygous for the HK1 variant (g.9712G-C; 142600.0003) identified by Hantke et al. (2009). Haplotype analysis confirmed a founder effect in this population. </p><p><strong><em>Retinitis Pigmentosa 79</em></strong></p><p>
|
|
In affected individuals from 5 families (UTAD003, UTAD936, UTAD952, MOGL1, and MOGL2) segregating autosomal dominant retinitis pigmentosa (RP79; 617460), Sullivan et al. (2014) identified heterozygosity for a missense mutation in the HK1 gene (E847K; 142600.0005) that segregated fully with disease in each family and was not found in public variant databases. None of the patients had extraocular manifestations and no systemic abnormalities in glycolysis were detected, even in 1 patient who was homozygous for the mutation. Sullivan et al. (2014) noted that the mutation is located outside the catalytic domains and suggested that the effect of the mutation was limited to the retina. </p><p>In affected individuals from a large 4-generation family of northern European ancestry with RP, Wang et al. (2014) identified heterozygosity for the E847K mutation in the HK1 gene. Affected individuals showed no signs of anemia, exercise intolerance, or cognitive defects. Biochemical assays revealed no obvious differences between the mutant and wildtype alleles in terms of enzymatic activity or mRNA and protein expression levels, suggesting that hexokinase deficiency is not likely to be the underlying mechanism. </p><p><strong><em>Neurodevelopmental Disorder with Visual Defects and Brain Anomalies</em></strong></p><p>
|
|
In 7 patients from 6 unrelated families with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; 618547), Okur et al. (2019) identified 4 different de novo heterozygous missense mutations in the HK1 gene (142600.0006-142600.0009). All mutations occurred at highly conserved residues in the N-terminal regulatory domain. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Blood cells from 2 unrelated patients had normal hexokinase activity, suggesting a different pathogenic mechanism. Other functional studies of the variant and studies of patient cells were not performed, but the authors postulated a gain-of-function effect. </p>
|
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</span>
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<div>
|
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<br />
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Schimke and Grossbard (1968) reviewed studies of hexokinase isozymes. </p>
|
|
</span>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>9 Selected Examples):</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 ANEMIA, CONGENITAL, NONSPHEROCYTIC HEMOLYTIC, 5</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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|
HK1, 96-BP DEL
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<br />
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ClinVar: RCV000016050
|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with nonspherocytic hemolytic anemia with the so-called HK-Melzo variant of hexokinase deficiency (CNSHA5; 235700), Bianchi and Magnani (1995) demonstrated compound heterozygosity for mutations in the HK1 gene: a 96-bp deletion of nucleotides 577 to 672 and a 1667T-C transition, resulting in a leu529-to-ser substitution (142600.0002). </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ANEMIA, CONGENITAL, NONSPHEROCYTIC HEMOLYTIC, 5</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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HK1, LEU529SER
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<br />
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SNP: rs137853249,
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ClinVar: RCV000016051
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</span>
|
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</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the leu529-to-ser (L529S) mutation in the HK1 gene that was found in compound heterozygous state in a patient with nonspherocytic hemolytic anemia due to hexokinase deficiency (CNSHA5; 235700) by Bianchi and Magnani (1995), see 142600.0001. </p>
|
|
</span>
|
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</div>
|
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NEUROPATHY, HEREDITARY MOTOR AND SENSORY, RUSSE TYPE</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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HK1, -3818-195G-C, AltT2 EXON
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<br />
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SNP: rs397514654,
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ClinVar: RCV000033228, RCV002054534, RCV002247416
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</span>
|
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</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all 34 individuals with the Russe type of hereditary motor and sensory neuropathy (HMSNR; 605285) who were studied, Hantke et al. (2009) identified 2 homozygous sequence changes in the HK1 gene, which maps within the candidate disease interval on chromosome 10q. One was a G-to-C transversion at a highly conserved nucleotide in the putative AltT2 exon located in the 5-prime region upstream of HK1 (-3818-195G-C, NM_033497; Chandler, 2013), and the other was an intronic G-to-A transition downstream of the AltT2 change; the G-to-A transition was not highly conserved, and thus not thought to be pathogenic. These 2 variants were found in heterozygous state in 5 of 790 control individuals representing a cross-section of the Gypsy population, but not in 233 Bulgarian controls. AltT2-containing transcripts in the mouse peripheral nerve were rare compared to the coding region of HK1. However, 6 of 8 testis AltT2-containing isoforms were found, with expression patterns differing between the peripheral nerve and the brain and between newborn and adult tissues in mice. There was no difference in HK1 mRNA in Schwann cells derived from patients or controls, and patient cells showed no evidence of HK1 enzyme activity compared to controls. Bioinformatic tools did not suggest an effect of the G-C change on HK1 gene splicing or binding sites for interacting proteins. However, there was evidence that the G-C change may cause a ter-to-tyr substitution in 1 upstream open reading frame that had a non-AUG start codon, which could potentially disrupt HK1 translation regulation. Hantke et al. (2009) speculated that non-OMM-binding HK1 may play a role in the pathogenesis of HMSNR. </p><p>Sevilla et al. (2013) found that 11 patients from 9 Roma Gypsy families with progressive hereditary motor and sensory neuropathy were homozygous for the HK1 variant (g.9712G-C) identified by Hantke et al. (2009), and haplotype analysis confirmed a founder effect in this population. The founding ancestor was estimated to have lived at the end of the 18th century, when a population split occurred from a tribal group and the Gypsy population in Spain increased under the rule of Charles III. </p>
|
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</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 ANEMIA, CONGENITAL, NONSPHEROCYTIC HEMOLYTIC, 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
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HK1, THR680SER
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<br />
|
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SNP: rs398122379,
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gnomAD: rs398122379,
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ClinVar: RCV000049268
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a girl, born of consanguineous parents, with severe nonspherocytic hemolytic anemia due to hexokinase deficiency (CNSHA5; 235700), who was previously reported by Rijksen et al. (1983), van Wijk et al. (2003) identified a homozygous c.2039C-G transversion in exon 15 of the HK1 gene, resulting in a thr680-to-ser (T680S) substitution at a highly conserved residue in the active site. The mutation, which segregated with the disorder in the family and was not found in 50 controls, was designated 'Utrecht.' In vitro studies of the mutant enzyme showed that it had a 2-fold decrease in affinity for Mg-ATP2 and a markedly decreased affinity for the inhibitor glucose-1,6-diphosphate. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 RETINITIS PIGMENTOSA 79</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HK1, GLU847LYS
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<br />
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SNP: rs777849213,
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gnomAD: rs777849213,
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ClinVar: RCV000487470, RCV001064496, RCV001075827, RCV004584389, RCV004740261
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected individuals from 5 families (UTAD003, UTAD936, UTAD952, MOGL1, and MOGL2) segregating autosomal dominant retinitis pigmentosa (RP79; 617460), Sullivan et al. (2014) identified heterozygosity for a c.2539G-A transition (c.2539G-A, NM_000188.2) in the HK1 gene, resulting in a glu847-to-lys (E847K) substitution at a highly conserved residue outside of known functional domains. The mutation segregated fully with disease in all families and was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases. Haplotype analysis in the 5 families, 3 of which were from the Acadian population in Louisiana, 1 French Canadian, and 1 Sicilian, demonstrated a shared 450-kb region on chromosome 10, suggesting a founder mutation. One patient in family UTAD003, who was homozygous for the mutation, was diagnosed at age 4 years due to profound nyctalopia; examination at age 33 showed visual acuity reduced to counting fingers in the right eye and 20/200 in the left eye, and he exhibited the classic features of RP on funduscopy, with severe retinal vascular attenuation, diffuse optic disc pallor, extensive and broadly distributed pigment epithelial atrophy with bone spicule accumulation throughout the fundus, and macular atrophy in both eyes. </p><p>In affected individuals from a large 4-generation family of European ancestry with RP, Wang et al. (2014) identified heterozygosity for the E847K mutation in the HK1 gene, which segregated with disease in the family with 85% penetrance and was not found in 11,000 in-house exomes. Two asymptomatic family members who also carried the mutation exhibited unaffected vision and no bone-spicule pigmentation at ages 37 and 78 years, respectively. Affected individuals showed no signs of anemia, exercise intolerance, or cognitive defects. Functional analysis in HEK293T cells showed that mutant hexokinase activity as well as mRNA and protein levels were similar to those of the wildtype protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HK1, GLY414GLU
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<br />
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SNP: rs1064795154,
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ClinVar: RCV000487002, RCV000850126
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 34-year-old woman (patient 1) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; 618547), Okur et al. (2019) identified a de novo heterozygous c.1241G-A transition (c.1241G-A, NM_000188.2) in the HK1 gene, resulting in a gly414-to-glu (G414E) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Functional studies of the variant and studies of patient cells were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0007 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HK1, LYS418GLU
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<br />
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SNP: rs1564557037,
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ClinVar: RCV000782118, RCV000850127, RCV001805835
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 9-year-old girl (patient 2) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; 618547), Okur et al. (2019) identified a de novo heterozygous c.1252A-G transition (c.1252A-G, NM_000188.2) in the HK1 gene, resulting in a lys418-to-glu (K418E) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Hexokinase activity in patient red cells was normal, suggesting a different pathogenic mechanism. Additional functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0008 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HK1, SER445LEU
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<br />
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SNP: rs1064794848,
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ClinVar: RCV000483739, RCV000850128, RCV001254702, RCV001266687, RCV001270352, RCV001770372, RCV003126749, RCV004816693
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 2 unrelated patients (patients 3 and 4) with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; 618547), Okur et al. (2019) identified a de novo heterozygous c.1334C-T transition (c.1334C-T, NM_000188.2) in the HK1 gene, resulting in a ser445-to-leu (S445L) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. Hexokinase activity in patient red cells derived from 1 of the patients was normal, suggesting a different pathogenic mechanism. Additional functional studies of the variant were not performed. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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HK1, THR457MET
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<br />
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SNP: rs1057517928,
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|
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ClinVar: RCV000413860, RCV000763213, RCV000850129, RCV001266327
|
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|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In an 8-year-old boy (patient 5) and 2 sibs who died at 1 year of age (patients 6 and 7), with neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA; 618547), Okur et al. (2019) identified a de novo heterozygous c.1370C-T transition (c.1370C-T, NM000188.2) in the HK1 gene, resulting in a thr457-to-met (T457M) substitution at a highly conserved residue in the N-terminal regulatory domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project, Exome Sequencing Project, ExAC, or gnomAD databases, or in an in-house database of over 100,000 exomes. The mutation occurred de novo in patient 5; paternal mosaicism in the blood was excluded in the sibs. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Chern (1976); Gitelman et al. (1980); Ritter et al. (1974); Rogers et
|
|
al. (1975); Snyder et al. (1984)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Amendola, C. R., Mahaffey, J. P., Parker, S. J., Ahearn, I. M., Chen, W.-C., Zhou, M., Court, H., Shi, J., Mendoza, S. L., Morten, M. J., Rothenberg, E., Gottlieb, E., Wadghiri, Y. Z., Possemato, R., Hubbard, S. R., Balmain, A., Kimmelman, A. C., Philips, M. R.
|
|
<strong>KRAS4A directly regulates hexokinase 1.</strong>
|
|
Nature 576: 482-486, 2019.
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|
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[PubMed: 31827279]
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|
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[Full Text: https://doi.org/10.1038/s41586-019-1832-9]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Andreoni, F., Ruzzo, A., Magnani, M.
|
|
<strong>Structure of the 5-prime region of the human hexokinase type I (HKI) gene and identification of an additional testis-specific HKI mRNA.</strong>
|
|
Biochim. Biophys. Acta 1493: 19-26, 2000.
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[PubMed: 10978502]
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[Full Text: https://doi.org/10.1016/s0167-4781(00)00147-0]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Bianchi, M., Crinelli, R., Serafini, G. Giammarini, C., Magnani, M.
|
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<strong>Molecular bases of hexokinase deficiency.</strong>
|
|
Biochim. Biophys. Acta 1360: 211-221, 1997.
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[PubMed: 9197463]
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[Full Text: https://doi.org/10.1016/s0925-4439(96)00080-4]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Bianchi, M., Magnani, M.
|
|
<strong>Hexokinase mutations that produce nonspherocytic hemolytic anemia.</strong>
|
|
Blood Cells Mol. Dis. 21: 2-8, 1995.
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[PubMed: 7655856]
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|
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[Full Text: https://doi.org/10.1006/bcmd.1995.0002]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Chandler, D.
|
|
<strong>Personal Communication.</strong>
|
|
Perth, Australia 3/16/2013.
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|
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</p>
|
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</li>
|
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|
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<li>
|
|
<p class="mim-text-font">
|
|
Chern, C. J.
|
|
<strong>Localization of the structural genes for hexokinase-1 and inorganic pyrophosphatase on region (pter-q24) of human chromosome 10.</strong>
|
|
Cytogenet. Cell Genet. 17: 338-342, 1976.
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|
|
[PubMed: 17494625]
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[Full Text: https://doi.org/10.1159/000130736]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Dallapiccola, B., Lungarotti, M. S., Magnani, M., Dacha, M.
|
|
<strong>Evidence of gene dosage effect for HK1 in the red cells of a patient with trisomy 10pter leads to p13.</strong>
|
|
Ann. Genet. 24: 45-47, 1981.
|
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|
|
[PubMed: 6971618]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Dallapiccola, B., Novelli, G., Micara, G., Delaroche, I., Moric-Petrovic, S., Magnani, M.
|
|
<strong>Regional mapping of hexokinase-1 within the short arm of chromosome 10.</strong>
|
|
Hum. Hered. 34: 156-160, 1984.
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|
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|
|
[PubMed: 6590458]
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|
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[Full Text: https://doi.org/10.1159/000153453]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Daniele, A., Altruda, F., Ferrone, M., Silengo, L., Romeo, G., Archidiacono, N., Rocchi, M.
|
|
<strong>Mapping of human hexokinase 1 gene to 10q11-qter.</strong>
|
|
Hum. Hered. 42: 107-110, 1992.
|
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|
|
|
[PubMed: 1572668]
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[Full Text: https://doi.org/10.1159/000154049]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Gelb, B. D., Worley, K. C., Griffin, L. D., Adams, V., Chinault, A. C., McCabe, E. R. B.
|
|
<strong>Characterization of human genomic artificial chromosome inserts containing hexokinase 1 coding information on chromosome 10.</strong>
|
|
Biochem. Med. Metab. Biol. 47: 265-269, 1992.
|
|
|
|
|
|
[PubMed: 1627358]
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|
|
[Full Text: https://doi.org/10.1016/0885-4505(92)90035-w]
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gitelman, B. J., Simpson, N. E.
|
|
<strong>Regional mapping of the locus for hexokinase-1 (HK1) to 10p11-q23 by gene dosage in human fibroblasts.</strong>
|
|
Hum. Genet. 60: 227-229, 1982.
|
|
|
|
|
|
[PubMed: 7106753]
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|
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[Full Text: https://doi.org/10.1007/BF00303008]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Gitelman, B. J., Tomkins, D. J., Partington, M. W., Roberts, M. H., Simpson, N. E.
|
|
<strong>Gene dosage studies of glutamic oxaloacetic transaminase (GOT) and hexokinase (HK) in two patients with possible partial trisomy 10q. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 32: 41A only, 1980.
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Griffin, L. D., Gelb, B. D., Wheeler, D. A., Davison, D., Adams, V., McCabe, E. R. B.
|
|
<strong>Mammalian hexokinase 1: evolutionary conservation and structure to function analysis.</strong>
|
|
Genomics 11: 1014-1024, 1991.
|
|
|
|
|
|
[PubMed: 1783373]
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|
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[Full Text: https://doi.org/10.1016/0888-7543(91)90027-c]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Hantke, J., Chandler, D., King, R., Wanders, R. J. A., Angelicheva, D., Tournev, I., McNamara, E., Kwa, M., Guergueltcheva, V., Kaneva, R., Baas, F., Kalaydjieva, L.
|
|
<strong>A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy--Russe (HMSNR).</strong>
|
|
Europ. J. Hum. Genet. 17: 1606-1614, 2009.
|
|
|
|
|
|
[PubMed: 19536174]
|
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|
|
[Full Text: https://doi.org/10.1038/ejhg.2009.99]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Mori, C., Nakamura, N., Welch, J. E., Shiota, K., Eddy, E. M.
|
|
<strong>Testis-specific expression of mRNAs for a unique human type 1 hexokinase lacking the porin-binding domain.</strong>
|
|
Molec. Reprod. Dev. 44: 14-22, 1996.
|
|
|
|
|
|
[PubMed: 8722688]
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|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-2795(199605)44:1<14::AID-MRD2>3.0.CO;2-W]
|
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Mori, C., Welch, J. E., Fulcher, K. D., O'Brien, D. A., Eddy, E. M.
|
|
<strong>Unique hexokinase messenger ribonucleic acids lacking the porin-binding domain are developmentally expressed in mouse spermatogenic cells.</strong>
|
|
Biol. Reprod. 49: 191-203, 1993.
|
|
|
|
|
|
[PubMed: 8396993]
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|
|
[Full Text: https://doi.org/10.1095/biolreprod49.2.191]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
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Wang, F., Wang, Y., Zhang, B., Zhao, L., Lyubasyuk, V., Wang, K., Xu, M., Li, Y., Wu, F., Wen, C., Bernstein, P. S., Lin, D., Zhu, S., Wang, H., Zhang, K., Chen, R.
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