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<title>
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Entry
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- *610982 - INVERTED FORMIN 2; INF2
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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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<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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<li class="dropdown-header">
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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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<a href="/search/advanced/geneMap"> Gene Map </a>
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Display:
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</form>
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<p />
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*610982</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="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li 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/610982">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div 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=ENSG00000203485;t=ENST00000392634" 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=64423" 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=610982" 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=ENSG00000203485;t=ENST00000392634" 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_001031714,NM_001426862,NM_001426863,NM_001426864,NM_001426865,NM_001426866,NM_001426867,NM_001426868,NM_022489,NM_032714,NR_190061" 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_022489" 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=610982" 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=08648&isoform_id=08648_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/INF2" 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/10438315,10440146,13544086,14249316,18027850,28375491,34528291,34809542,40674056,50949486,89027955,89027957,89027959,95105614,119602277,119602278,119602279,119602280,119602281,149999378,149999380,158261189,166215588,2643756722,2643756728,2643756730,2643756732,2643756736,2643756748,2643756754" 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/Q27J81" 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=64423" 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=ENSG00000203485;t=ENST00000392634" 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=INF2" 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=INF2" 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+64423" 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/INF2" 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:64423" 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/64423" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr14&hgg_gene=ENST00000392634.9&hgg_start=104681133&hgg_end=104722535&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:23791" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=610982[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=610982[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/INF2/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/ENSG00000203485" 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=INF2" 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=INF2" 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=INF2" 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=INF2&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/PA162392025" 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:23791" 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/FBgn0053556.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:1917685" 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/INF2#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:1917685" 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/64423/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=64423" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-140711-5" 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:64423" 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=INF2&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> 722294004<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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610982
|
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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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INVERTED FORMIN 2; INF2
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FORMIN, INVERTED, 2<br />
|
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CHROMOSOME 14 OPEN READING FRAME 173; C14ORF173
|
|
</span>
|
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</h4>
|
|
</div>
|
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</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=INF2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">INF2</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/590?start=-3&limit=10&highlight=590">14q32.33</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:104681133-104722535&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">14:104,681,133-104,722,535</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 />
|
|
</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</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>
|
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Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614455,613237" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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Phenotype <br /> MIM number
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14q32.33
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Charcot-Marie-Tooth disease, dominant intermediate E
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<a href="/entry/614455"> 614455 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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Glomerulosclerosis, focal segmental, 5
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<a href="/entry/613237"> 613237 </a>
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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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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/610982" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/610982" 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>Actin filaments grow only when actin monomers have access to the fast-growing barbed end of the filament. The geometry of the filament network depends on the actions of the ARP2/3 complex (<a href="/entry/604221">604221</a>) and members of the formin family, such as INF2. The ARP2/3 complex binds to the sides of preexisting filaments and nucleates filaments whose barbed ends are quickly blocked by capping proteins, producing brush-like structures, such as those found at the leading edges of crawling cells. In contrast, formins bind to the barbed ends of growing filaments and protect them from capping, creating long filaments that can be cross-linked into bundles, such as those found in actin cables of yeast. Interaction of formins with actin barbed ends occurs through the formin homology-2 (FH2) domain. FH2 domains accelerate filament nucleation, move with the barbed end as the filament grows, and block capping of the barbed end by proteins such as gelsolin (GSN; <a href="/entry/137350">137350</a>). The FH1 domain of formins binds to profilin (see <a href="/entry/176610">176610</a>) and accelerates elongation from the FH2-bound barbed ends (<a href="#1" class="mim-tip-reference" title="Bindschadler, M., McGrath, J. L. <strong>Formin' new ideas about actin filament generation.</strong> Proc. Nat. Acad. Sci. 101: 14685-14686, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15466701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15466701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15466701[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0406317101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15466701">Bindschadler and McGrath, 2004</a>; <a href="#4" class="mim-tip-reference" title="Chhabra, E. S., Higgs, H. N. <strong>INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization.</strong> J. Biol. Chem. 281: 26754-26767, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16818491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16818491</a>] [<a href="https://doi.org/10.1074/jbc.M604666200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16818491">Chhabra and Higgs, 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16818491+15466701" 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>By searching databases for FH2 domain sequences, <a href="#6" class="mim-tip-reference" title="Higgs, H. N., Peterson, K. J. <strong>Phylogenetic analysis of the formin homology 2 domain.</strong> Molec. Biol. Cell 16: 1-13, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509653</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15509653[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/10.1091/mbc.e04-07-0565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509653">Higgs and Peterson (2005)</a> identified mouse and human INF2, a member of the inverted formin group. Inverted formins have an N-terminal FH2 domain rather than the C-terminal FH2 domain found in all other formins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15509653" 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 database analysis and RT-PCR, <a href="#4" class="mim-tip-reference" title="Chhabra, E. S., Higgs, H. N. <strong>INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization.</strong> J. Biol. Chem. 281: 26754-26767, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16818491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16818491</a>] [<a href="https://doi.org/10.1074/jbc.M604666200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16818491">Chhabra and Higgs (2006)</a> cloned full-length mouse Inf2. The deduced 1,274-amino acid protein has an N-terminal diaphanous inhibitory domain (DID), followed by an FH1 domain, an FH2 domain, and a C-terminal diaphanous autoregulatory domain (DAD)/ WASP (<a href="/entry/300392">300392</a>) homology-2 (WH2) domain. Thus, Inf2 is not an inverted formin, but is most similar to diaphanous formins (e.g., DIAPH1; <a href="/entry/602121">602121</a>), which are regulated by autoinhibition via DID-DAD interaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16818491" 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 immunohistochemical staining, <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> demonstrated robust IFN2 expression in peripheral nerve Schwann cells and light staining in some axons. INF2 was also expressed predominantly in podocytes in the kidney, as well as in some tubules, but not in vessels. INF2 colocalized with the myelin and lymphocyte protein (MAL; <a href="/entry/188860">188860</a>) in human peripheral nerve and mouse Schwann cells, and with MAL2 (<a href="/entry/609684">609684</a>) in human podocytes. MAL was not present in glomeruli. In HeLa cells, INF2 showed perinuclear localization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#5" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 1/3/2025."None>Gross (2025)</a> mapped the INF2 gene to chromosome 14q32.33 based on an alignment of the INF2 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC006173" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC006173</a>) with the genomic sequence (GRCh38).</p></div>
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<p>Using fluorescence microscopy to study the effects of various constructs containing domains of mouse Inf2 on actin elongation and nucleation, <a href="#4" class="mim-tip-reference" title="Chhabra, E. S., Higgs, H. N. <strong>INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization.</strong> J. Biol. Chem. 281: 26754-26767, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16818491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16818491</a>] [<a href="https://doi.org/10.1074/jbc.M604666200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16818491">Chhabra and Higgs (2006)</a> showed that Inf2 interacted with actin through a region C-terminal to the FH2 domain. This region, in combination with the FH2 domain, accelerated both polymerization and depolymerization of actin filaments. Depolymerization resulted from actin monomer-binding ability of the WH2 domain and a severing activity that depended on attachment of the FH2 domain to the C terminus. Phosphate inhibited both depolymerization and severing, suggesting that phosphate release from actin subunits in the filament triggers depolymerization. Mutation of the WH2 domain abrogated depolymerization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16818491" 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="#7" class="mim-tip-reference" title="Korobova, F., Ramabhadran, V., Higgs, H. N. <strong>An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2.</strong> Science 339: 464-467, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349293[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/10.1126/science.1228360" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349293">Korobova et al. (2013)</a> found that actin polymerization through endoplasmic reticulum (ER)-localized INF2 was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of DRP1 (<a href="/entry/603850">603850</a>). Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows DRP1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease (<a href="/entry/614455">614455</a>), <a href="#7" class="mim-tip-reference" title="Korobova, F., Ramabhadran, V., Higgs, H. N. <strong>An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2.</strong> Science 339: 464-467, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349293[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/10.1126/science.1228360" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23349293">Korobova et al. (2013)</a> concluded that their results provided a potential cellular mechanism for this disease state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23349293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Focal Segmental Glomerulosclerosis 5</em></strong></p><p>
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In 2 large families segregating autosomal dominant focal segmental glomerulosclerosis mapping to chromosome 14q32 (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> sequenced 15 candidate genes and identified heterozygous missense mutations in the INF2 gene in both families that segregated with disease (<a href="#0001">610982.0001</a> and <a href="#0002">610982.0002</a>, respectively). Sequencing of the INF2 gene in 91 unrelated individuals with familial FSGS revealed 9 additional families with heterozygous mutations in the INF2 gene that segregated with disease (see, e.g., <a href="#0003">610982.0003</a>-<a href="#0005">610982.0005</a>). <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> noted that all 9 of the disease-segregating substitutions are located at conserved residues within the DID (diaphanous-inhibitory domain) region of INF2, with 7 residing in close proximity to each other in exon 4 of the gene. Studies in transfected podocytes demonstrated alterations in the subcellular localization of INF2 and the pattern of distribution of the associated F-actin with mutant forms of INF2 compared to wildtype, as well as less prominent actin filament bundles on electron micrographs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" 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>Dominant Intermediate Charcot-Marie-Tooth Disease E with Focal Segmental Glomerulosclerosis</em></strong></p><p>
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In 12 (75%) of 16 index patients with dominant intermediate Charcot-Marie-Tooth disease E (CMTDIE; <a href="/entry/614455">614455</a>) with focal segmental glomerulosclerosis (FSGS), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified 9 novel heterozygous mutations in the INF2 gene (see, e.g., <a href="#0006">610982.0006</a>-<a href="#0011">610982.0011</a>). All mutations were located in exons 2 and 3, which encode the diaphanous inhibitory domain (DID), and most of them were between nucleotides 300 and 500 in the second and third armadillo repeats. These mutations were located in distinct areas from those associated with isolated FSGS5, most of which are located downstream of nucleotide 500 in the fourth armadillo repeat domain. The 12 index patients with INF2 mutations reported by <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> presented with proteinuria at a median age of 18 years (range, 10-21 years), and 11 developed end-stage renal disease at a median age of 21 years (range, 12-47 years). Renal biopsies showed FSGS. The median age at onset of neurologic dysfunction was 13 years (range, 5-28 years), and all had distal muscle atrophy and weakness affecting the lower limbs. Some had upper limb involvement as well. Neurophysiologic studies and sural nerve biopsies indicated an intermediate form of CMT. Four patients also had mild to moderate sensorineural hearing loss. INF2 mutations were not found in 50 patients with CMT without renal involvement. In vitro functional expression studies by <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> showed that mutant INF2 was abnormally dispersed throughout the cytoplasm, resulting in a broader cytoplasmic distribution of MAL. Cells expressing mutant INF2 exhibited less cortical actin and a reduced number of long actin stress fibers compared to wildtype, suggesting a disorganized microtubule network. Finally, INF2 mutants showed an enhanced interaction with CDC42 (<a href="/entry/116952">116952</a>), an actin-regulating Rho-GTPase known to interact with the INF2 DID domain, resulting in altered intracellular localization of CDC42. <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> concluded that mutant INF2 disrupts actin dynamics in peripheral Schwann cells, leading to disturbed myelin formation and maintenance and resulting in CMT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#9" class="mim-tip-reference" title="Subramanian, B., Williams, S., Karp, S., Hennino, M. F., Jacas, S., Lee, M., Riella, C. V., Alper, S. L., Higgs, H. N., Pollak, M. R. <strong>INF2 mutations cause kidney disease through a gain-of-function mechanism.</strong> Sci. Adv. 10: eadr1017, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39536114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39536114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=39536114[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/10.1126/sciadv.adr1017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39536114">Subramanian et al. (2024)</a> found that knockin mice heterozygous for the FSGS-associated arg218-to-gln (R218Q; <a href="#0002">610982.0002</a>) mutation in the DID of Inf2 developed kidney disease, whereas mice heterozygous for Inf2 knockout did not, indicating that Inf2-mediated kidney disease occurred due to gain-of-function effects of mutant Inf2. Analysis with podocytes showed that mutation in the DID of Inf2 conferred a gain-of-function effect by altering the localization of wildtype Inf2 and Inf2 actin-polymerizing activity, leading to activity at abnormal sites. RNA sequencing analysis identified cellular processes that were altered by the gain-of-function effect of mutant Inf2, and mutant mouse podocytes displayed altered cell adhesion and mitochondrial morphology. Moreover, kidney organoid-derived podocytes from a patient with an INF2 mutation recapitulated the mouse disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39536114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<p>In affected members of 2 large Canadian families segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in a ser186-to-pro (S186P) substitution at a conserved residue within the autoinhibitory DID region. Transfection studies in cultured podocytes showed a slightly more diffuse distribution of INF2 with a more vermiform appearance than wildtype, and less prominent stress fibers and cortical actin compared to wildtype. The mutation was not found in 282 controls. Age at diagnosis in the 2 families ranged from 12 years to 67 years; 12 of 28 affected individuals developed end-stage renal disease, with age of onset ranging from 20 years to 67 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of a large family segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg218-to-gln (R218Q) substitution at a conserved residue within the DID. Structural modeling revealed that the R218 residue lies close to the DAD-binding region of the DID, and transfection studies in cultured podocytes showed a finer, more diffuse distribution of INF2 and less prominent stress fibers and cortical actin with mutant compared to wildtype INF2. The mutation was not found in 682 control chromosomes. Age at diagnosis in this kindred ranged from 22 years to 45 years; 4 of 10 affected individuals developed end-stage renal disease, with age of onset ranging from 23 years to 30 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#9" class="mim-tip-reference" title="Subramanian, B., Williams, S., Karp, S., Hennino, M. F., Jacas, S., Lee, M., Riella, C. V., Alper, S. L., Higgs, H. N., Pollak, M. R. <strong>INF2 mutations cause kidney disease through a gain-of-function mechanism.</strong> Sci. Adv. 10: eadr1017, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39536114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39536114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=39536114[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/10.1126/sciadv.adr1017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39536114">Subramanian et al. (2024)</a> found that knockin mice heterozygous for the FSGS-associated arg218-to-gln (R218Q; <a href="#0002">610982.0002</a>) mutation in the DID of Inf2 developed kidney disease, whereas mice heterozygous for Inf2 knockout did not, indicating that Inf2-mediated kidney disease occurred due to gain-of-function effects of mutant Inf2. Analysis with podocytes showed that mutation in the DID of Inf2 conferred a gain-of-function effect by altering the localization of wildtype Inf2 and Inf2 actin-polymerizing activity, leading to activity at abnormal sites. RNA sequencing analysis identified cellular processes that were altered by the gain-of-function effect of mutant Inf2, and mutant mouse podocytes displayed altered cell adhesion and mitochondrial morphology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39536114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606878 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606878;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=rs267606878" 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=rs267606878" 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=RCV000001107 OR RCV001380436 OR RCV003987303" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001107, RCV001380436, RCV003987303" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001107...</a>
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<p>In 2 African-American brothers with focal segmental glomerulosclerosis (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg218-to-trp (R218W) substitution at a conserved residue within the autoinhibitory DID region. Structural modeling revealed that the R218 residue lies close to the DAD-binding region of the DID. The mutation was not found in 282 controls. The brothers were diagnosed at 27 and 33 years of age, respectively, and developed end-stage renal disease at 30 and 40 years of age, respectively. Their affected father was deceased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" 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">rs267606879 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606879;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=rs267606879" 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=rs267606879" 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=RCV000001108 OR RCV001380435 OR RCV002293971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001108, RCV001380435, RCV002293971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001108...</a>
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<p>In affected members of 2 large families segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg214-to-his (R214H) substitution at a conserved residue within the autoinhibitory DID region. Structural modeling revealed that the R214 residue lies close to the DAD-binding region of the DID. The mutation was not found in 282 controls. Age at diagnosis in the 2 families ranged from 12 years to 72 years; 4 of 12 affected individuals developed end-stage renal disease, with age of onset ranging from 17 years to 60 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" 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">rs267606880 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606880;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=rs267606880" 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=rs267606880" 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=RCV000001109" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001109" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001109</a>
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<p>In a sister and brother with focal segmental glomerulosclerosis (FSGS5; <a href="/entry/613237">613237</a>), <a href="#3" class="mim-tip-reference" title="Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J. <strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong> Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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/ng.505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20023659">Brown et al. (2010)</a> identified a heterozygous alteration in exon 2 of the INF2 gene, resulting in a leu42-to-pro (L42P) substitution at a conserved residue within the autoinhibitory DID region. Their affected father was also heterozygous for the mutation, which was not found in 341 controls. Diagnosis in this family occurred between 11 to 13 years of age, and all 3 affected individuals developed end-stage renal disease by 13 to 14 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20023659" 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 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</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">rs387907034 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907034;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=rs387907034" 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=rs387907034" 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=RCV000023849 OR RCV003488347 OR RCV003764633" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023849, RCV003488347, RCV003764633" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023849...</a>
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<p>In a Caucasian Moroccan patient with dominant intermediate Charcot-Marie-Tooth disease E (CMTDIE; <a href="/entry/614455">614455</a>) with focal segmental glomerulosclerosis, <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a de novo heterozygous 310T-C transition in exon 2 of the INF2 gene, resulting in a cys104-to-arg (C104R) substitution in a highly conserved residue in the N-terminal diaphanous-inhibitory domain (DID). The mutation was not found in 670 control chromosomes. The same residue was mutated in another patient (C104F; <a href="#0007">610982.0007</a>) and in affected members of a family (C104W; <a href="#0008">610982.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" 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">rs387907035 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907035;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=rs387907035" 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=rs387907035" 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=RCV000023850" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023850" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023850</a>
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<p>In a Caucasian/African patient from the French West Indies with CMTDIE (<a href="/entry/614455">614455</a>), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a heterozygous 311G-T transversion in exon 2 of the INF2 gene, resulting in a cys104-to-phe (C104F) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes. The same residue was mutated in another patient (C104R; <a href="#0006">610982.0006</a>) and in affected members of a family (C104W; <a href="#0008">610982.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" 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> rs387907036 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907036;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/rs387907036?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=rs387907036" 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=rs387907036" 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=RCV000023851 OR RCV001228020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023851, RCV001228020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023851...</a>
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<p>In affected members of a Caucasian Canadian family with CMTDIE (<a href="/entry/614455">614455</a>) (<a href="#8" class="mim-tip-reference" title="Lemieux, G., Neemeh, J. A. <strong>Charcot-Marie-Tooth disease and nephritis.</strong> Canad. Med. Assoc. J. 97: 1193-1198, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6054293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6054293</a>]" pmid="6054293">Lemieux and Neemeh, 1967</a>), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a heterozygous 312C-G transversion in exon 2 of the INF2 gene, resulting in a cys104-to-trp (C104W) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes. The same residue was mutated in 2 other unrelated patients with sporadic disease (C104R, <a href="#0006">610982.0006</a> and C104F, <a href="#0007">610982.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22187985+6054293" 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">rs387907037 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907037;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=rs387907037" 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=rs387907037" 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=RCV000023852 OR RCV000235466 OR RCV001378421 OR RCV002362594" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023852, RCV000235466, RCV001378421, RCV002362594" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023852...</a>
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<p>In 2 unrelated Caucasian patients from Portugal and France, respectively, with CMTDIE (<a href="/entry/614455">614455</a>), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a heterozygous 383T-C transition in exon 2 of the INF2 gene, resulting in a leu128-to-pro (L128P) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes, and was confirmed to be de novo in 1 of the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" 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">rs387907038 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907038;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=rs387907038" 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=rs387907038" 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=RCV000023853" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023853" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023853</a>
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<p>In affected members of a Caucasian French family with CMTDIE (<a href="/entry/614455">614455</a>), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a heterozygous 395T-C transition in exon 3 of the INF2 gene, resulting in a leu132-to-arg (L132R) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was also identified in a patient with sporadic disease, but was not found in 670 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" 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">rs1555373599 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555373599;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=rs1555373599" 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=rs1555373599" 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=RCV000543208 OR RCV002286575" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000543208, RCV002286575" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000543208...</a>
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<p>In affected members of 2 Caucasian families with CMTDIE (<a href="/entry/614455">614455</a>), <a href="#2" class="mim-tip-reference" title="Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others. <strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong> New Eng. J. Med. 365: 2377-2388, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>] [<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22187985">Boyer et al. (2011)</a> identified a heterozygous 9-bp deletion (490_498del) in exon 3 of the INF2 gene, resulting in an in-frame deletion of 3 conserved residues (ala164-asp166). The mutation was not found in 670 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" 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>Formin' new ideas about actin filament generation.</strong>
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Proc. Nat. Acad. Sci. 101: 14685-14686, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15466701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15466701</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15466701[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=15466701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0406317101" target="_blank">Full Text</a>]
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Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others.
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<strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong>
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New Eng. J. Med. 365: 2377-2388, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22187985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22187985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22187985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1109122" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Brown2010" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J.
|
|
<strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong>
|
|
Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.
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|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20023659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20023659</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20023659[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=20023659" 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/ng.505" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Chhabra2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chhabra, E. S., Higgs, H. N.
|
|
<strong>INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization.</strong>
|
|
J. Biol. Chem. 281: 26754-26767, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16818491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16818491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16818491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M604666200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
|
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<a id="Gross2025" class="mim-anchor"></a>
|
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<div class="mim-changed mim-change">
|
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<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1/3/2025.
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Higgs2005" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Higgs, H. N., Peterson, K. J.
|
|
<strong>Phylogenetic analysis of the formin homology 2 domain.</strong>
|
|
Molec. Biol. Cell 16: 1-13, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509653</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15509653[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=15509653" 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/10.1091/mbc.e04-07-0565" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Korobova2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Korobova, F., Ramabhadran, V., Higgs, H. N.
|
|
<strong>An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2.</strong>
|
|
Science 339: 464-467, 2013.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23349293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23349293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23349293[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=23349293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1126/science.1228360" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
|
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<a id="Lemieux1967" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Lemieux, G., Neemeh, J. A.
|
|
<strong>Charcot-Marie-Tooth disease and nephritis.</strong>
|
|
Canad. Med. Assoc. J. 97: 1193-1198, 1967.
|
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|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6054293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6054293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6054293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Subramanian2024" class="mim-anchor"></a>
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<div class="mim-changed mim-change">
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<p class="mim-text-font">
|
|
Subramanian, B., Williams, S., Karp, S., Hennino, M. F., Jacas, S., Lee, M., Riella, C. V., Alper, S. L., Higgs, H. N., Pollak, M. R.
|
|
<strong>INF2 mutations cause kidney disease through a gain-of-function mechanism.</strong>
|
|
Sci. Adv. 10: eadr1017, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39536114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39536114</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=39536114[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=39536114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/sciadv.adr1017" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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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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Matthew B. Gross - updated : 01/03/2025
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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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Bao Lige - updated : 01/03/2025<br>Ada Hamosh - updated : 2/21/2013<br>Cassandra L. Kniffin - updated : 1/30/2012<br>Marla J. F. O'Neill - updated : 1/29/2010<br>Matthew B. Gross - updated : 4/26/2007
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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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Alan F. Scott : 4/26/2007
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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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mgross : 01/03/2025
|
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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">
|
|
mgross : 01/03/2025<br>carol : 03/11/2015<br>alopez : 2/26/2013<br>terry : 2/21/2013<br>terry : 1/29/2013<br>alopez : 3/22/2012<br>carol : 1/30/2012<br>ckniffin : 1/30/2012<br>mgross : 5/17/2010<br>alopez : 1/29/2010<br>alopez : 1/29/2010<br>mgross : 4/26/2007
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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> 610982
|
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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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INVERTED FORMIN 2; INF2
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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-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
FORMIN, INVERTED, 2<br />
|
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CHROMOSOME 14 OPEN READING FRAME 173; C14ORF173
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: INF2</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> 722294004;
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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>
|
|
Cytogenetic location: 14q32.33
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 14:104,681,133-104,722,535 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
|
</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
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<tr>
|
|
<td rowspan="2">
|
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<span class="mim-font">
|
|
14q32.33
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, dominant intermediate E
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
614455
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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>
|
|
<span class="mim-font">
|
|
Glomerulosclerosis, focal segmental, 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613237
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
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|
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|
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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>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<span class="mim-text-font">
|
|
<p>Actin filaments grow only when actin monomers have access to the fast-growing barbed end of the filament. The geometry of the filament network depends on the actions of the ARP2/3 complex (604221) and members of the formin family, such as INF2. The ARP2/3 complex binds to the sides of preexisting filaments and nucleates filaments whose barbed ends are quickly blocked by capping proteins, producing brush-like structures, such as those found at the leading edges of crawling cells. In contrast, formins bind to the barbed ends of growing filaments and protect them from capping, creating long filaments that can be cross-linked into bundles, such as those found in actin cables of yeast. Interaction of formins with actin barbed ends occurs through the formin homology-2 (FH2) domain. FH2 domains accelerate filament nucleation, move with the barbed end as the filament grows, and block capping of the barbed end by proteins such as gelsolin (GSN; 137350). The FH1 domain of formins binds to profilin (see 176610) and accelerates elongation from the FH2-bound barbed ends (Bindschadler and McGrath, 2004; Chhabra and Higgs, 2006). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<span class="mim-text-font">
|
|
<p>By searching databases for FH2 domain sequences, Higgs and Peterson (2005) identified mouse and human INF2, a member of the inverted formin group. Inverted formins have an N-terminal FH2 domain rather than the C-terminal FH2 domain found in all other formins. </p><p>By database analysis and RT-PCR, Chhabra and Higgs (2006) cloned full-length mouse Inf2. The deduced 1,274-amino acid protein has an N-terminal diaphanous inhibitory domain (DID), followed by an FH1 domain, an FH2 domain, and a C-terminal diaphanous autoregulatory domain (DAD)/ WASP (300392) homology-2 (WH2) domain. Thus, Inf2 is not an inverted formin, but is most similar to diaphanous formins (e.g., DIAPH1; 602121), which are regulated by autoinhibition via DID-DAD interaction. </p><p>By immunohistochemical staining, Boyer et al. (2011) demonstrated robust IFN2 expression in peripheral nerve Schwann cells and light staining in some axons. INF2 was also expressed predominantly in podocytes in the kidney, as well as in some tubules, but not in vessels. INF2 colocalized with the myelin and lymphocyte protein (MAL; 188860) in human peripheral nerve and mouse Schwann cells, and with MAL2 (609684) in human podocytes. MAL was not present in glomeruli. In HeLa cells, INF2 showed perinuclear localization. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2025) mapped the INF2 gene to chromosome 14q32.33 based on an alignment of the INF2 sequence (GenBank BC006173) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Using fluorescence microscopy to study the effects of various constructs containing domains of mouse Inf2 on actin elongation and nucleation, Chhabra and Higgs (2006) showed that Inf2 interacted with actin through a region C-terminal to the FH2 domain. This region, in combination with the FH2 domain, accelerated both polymerization and depolymerization of actin filaments. Depolymerization resulted from actin monomer-binding ability of the WH2 domain and a severing activity that depended on attachment of the FH2 domain to the C terminus. Phosphate inhibited both depolymerization and severing, suggesting that phosphate release from actin subunits in the filament triggers depolymerization. Mutation of the WH2 domain abrogated depolymerization. </p><p>Korobova et al. (2013) found that actin polymerization through endoplasmic reticulum (ER)-localized INF2 was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of DRP1 (603850). Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows DRP1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease (614455), Korobova et al. (2013) concluded that their results provided a potential cellular mechanism for this disease state. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Focal Segmental Glomerulosclerosis 5</em></strong></p><p>
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In 2 large families segregating autosomal dominant focal segmental glomerulosclerosis mapping to chromosome 14q32 (FSGS5; 613237), Brown et al. (2010) sequenced 15 candidate genes and identified heterozygous missense mutations in the INF2 gene in both families that segregated with disease (610982.0001 and 610982.0002, respectively). Sequencing of the INF2 gene in 91 unrelated individuals with familial FSGS revealed 9 additional families with heterozygous mutations in the INF2 gene that segregated with disease (see, e.g., 610982.0003-610982.0005). Brown et al. (2010) noted that all 9 of the disease-segregating substitutions are located at conserved residues within the DID (diaphanous-inhibitory domain) region of INF2, with 7 residing in close proximity to each other in exon 4 of the gene. Studies in transfected podocytes demonstrated alterations in the subcellular localization of INF2 and the pattern of distribution of the associated F-actin with mutant forms of INF2 compared to wildtype, as well as less prominent actin filament bundles on electron micrographs. </p><p><strong><em>Dominant Intermediate Charcot-Marie-Tooth Disease E with Focal Segmental Glomerulosclerosis</em></strong></p><p>
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|
In 12 (75%) of 16 index patients with dominant intermediate Charcot-Marie-Tooth disease E (CMTDIE; 614455) with focal segmental glomerulosclerosis (FSGS), Boyer et al. (2011) identified 9 novel heterozygous mutations in the INF2 gene (see, e.g., 610982.0006-610982.0011). All mutations were located in exons 2 and 3, which encode the diaphanous inhibitory domain (DID), and most of them were between nucleotides 300 and 500 in the second and third armadillo repeats. These mutations were located in distinct areas from those associated with isolated FSGS5, most of which are located downstream of nucleotide 500 in the fourth armadillo repeat domain. The 12 index patients with INF2 mutations reported by Boyer et al. (2011) presented with proteinuria at a median age of 18 years (range, 10-21 years), and 11 developed end-stage renal disease at a median age of 21 years (range, 12-47 years). Renal biopsies showed FSGS. The median age at onset of neurologic dysfunction was 13 years (range, 5-28 years), and all had distal muscle atrophy and weakness affecting the lower limbs. Some had upper limb involvement as well. Neurophysiologic studies and sural nerve biopsies indicated an intermediate form of CMT. Four patients also had mild to moderate sensorineural hearing loss. INF2 mutations were not found in 50 patients with CMT without renal involvement. In vitro functional expression studies by Boyer et al. (2011) showed that mutant INF2 was abnormally dispersed throughout the cytoplasm, resulting in a broader cytoplasmic distribution of MAL. Cells expressing mutant INF2 exhibited less cortical actin and a reduced number of long actin stress fibers compared to wildtype, suggesting a disorganized microtubule network. Finally, INF2 mutants showed an enhanced interaction with CDC42 (116952), an actin-regulating Rho-GTPase known to interact with the INF2 DID domain, resulting in altered intracellular localization of CDC42. Boyer et al. (2011) concluded that mutant INF2 disrupts actin dynamics in peripheral Schwann cells, leading to disturbed myelin formation and maintenance and resulting in CMT. </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>Animal Model</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>Subramanian et al. (2024) found that knockin mice heterozygous for the FSGS-associated arg218-to-gln (R218Q; 610982.0002) mutation in the DID of Inf2 developed kidney disease, whereas mice heterozygous for Inf2 knockout did not, indicating that Inf2-mediated kidney disease occurred due to gain-of-function effects of mutant Inf2. Analysis with podocytes showed that mutation in the DID of Inf2 conferred a gain-of-function effect by altering the localization of wildtype Inf2 and Inf2 actin-polymerizing activity, leading to activity at abnormal sites. RNA sequencing analysis identified cellular processes that were altered by the gain-of-function effect of mutant Inf2, and mutant mouse podocytes displayed altered cell adhesion and mitochondrial morphology. Moreover, kidney organoid-derived podocytes from a patient with an INF2 mutation recapitulated the mouse disease phenotype. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>11 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0001 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 5</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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INF2, SER186PRO
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<br />
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SNP: rs267606877,
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|
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ClinVar: RCV000001105, RCV003934790
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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 affected members of 2 large Canadian families segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; 613237), Brown et al. (2010) identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in a ser186-to-pro (S186P) substitution at a conserved residue within the autoinhibitory DID region. Transfection studies in cultured podocytes showed a slightly more diffuse distribution of INF2 with a more vermiform appearance than wildtype, and less prominent stress fibers and cortical actin compared to wildtype. The mutation was not found in 282 controls. Age at diagnosis in the 2 families ranged from 12 years to 67 years; 12 of 28 affected individuals developed end-stage renal disease, with age of onset ranging from 20 years to 67 years. </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>.0002 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 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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|
|
INF2, ARG218GLN
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<br />
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|
|
SNP: rs267607183,
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|
|
ClinVar: RCV000001106, RCV000681691, RCV001239762, RCV002293970, RCV003352745, RCV004814789
|
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|
|
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|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large family segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; 613237), Brown et al. (2010) identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg218-to-gln (R218Q) substitution at a conserved residue within the DID. Structural modeling revealed that the R218 residue lies close to the DAD-binding region of the DID, and transfection studies in cultured podocytes showed a finer, more diffuse distribution of INF2 and less prominent stress fibers and cortical actin with mutant compared to wildtype INF2. The mutation was not found in 682 control chromosomes. Age at diagnosis in this kindred ranged from 22 years to 45 years; 4 of 10 affected individuals developed end-stage renal disease, with age of onset ranging from 23 years to 30 years. </p>
|
|
|
|
<div class="mim-changed mim-change"><p>Subramanian et al. (2024) found that knockin mice heterozygous for the FSGS-associated arg218-to-gln (R218Q; 610982.0002) mutation in the DID of Inf2 developed kidney disease, whereas mice heterozygous for Inf2 knockout did not, indicating that Inf2-mediated kidney disease occurred due to gain-of-function effects of mutant Inf2. Analysis with podocytes showed that mutation in the DID of Inf2 conferred a gain-of-function effect by altering the localization of wildtype Inf2 and Inf2 actin-polymerizing activity, leading to activity at abnormal sites. RNA sequencing analysis identified cellular processes that were altered by the gain-of-function effect of mutant Inf2, and mutant mouse podocytes displayed altered cell adhesion and mitochondrial morphology. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, ARG218TRP
|
|
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|
|
<br />
|
|
|
|
SNP: rs267606878,
|
|
|
|
|
|
|
|
ClinVar: RCV000001107, RCV001380436, RCV003987303
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 African-American brothers with focal segmental glomerulosclerosis (FSGS5; 613237), Brown et al. (2010) identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg218-to-trp (R218W) substitution at a conserved residue within the autoinhibitory DID region. Structural modeling revealed that the R218 residue lies close to the DAD-binding region of the DID. The mutation was not found in 282 controls. The brothers were diagnosed at 27 and 33 years of age, respectively, and developed end-stage renal disease at 30 and 40 years of age, respectively. Their affected father was deceased. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, ARG214HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606879,
|
|
|
|
|
|
|
|
ClinVar: RCV000001108, RCV001380435, RCV002293971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 large families segregating autosomal dominant focal segmental glomerulosclerosis (FSGS5; 613237), Brown et al. (2010) identified a heterozygous alteration in exon 4 of the INF2 gene, resulting in an arg214-to-his (R214H) substitution at a conserved residue within the autoinhibitory DID region. Structural modeling revealed that the R214 residue lies close to the DAD-binding region of the DID. The mutation was not found in 282 controls. Age at diagnosis in the 2 families ranged from 12 years to 72 years; 4 of 12 affected individuals developed end-stage renal disease, with age of onset ranging from 17 years to 60 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, LEU42PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606880,
|
|
|
|
|
|
|
|
ClinVar: RCV000001109
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother with focal segmental glomerulosclerosis (FSGS5; 613237), Brown et al. (2010) identified a heterozygous alteration in exon 2 of the INF2 gene, resulting in a leu42-to-pro (L42P) substitution at a conserved residue within the autoinhibitory DID region. Their affected father was also heterozygous for the mutation, which was not found in 341 controls. Diagnosis in this family occurred between 11 to 13 years of age, and all 3 affected individuals developed end-stage renal disease by 13 to 14 years of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, CYS104ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907034,
|
|
|
|
|
|
|
|
ClinVar: RCV000023849, RCV003488347, RCV003764633
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Caucasian Moroccan patient with dominant intermediate Charcot-Marie-Tooth disease E (CMTDIE; 614455) with focal segmental glomerulosclerosis, Boyer et al. (2011) identified a de novo heterozygous 310T-C transition in exon 2 of the INF2 gene, resulting in a cys104-to-arg (C104R) substitution in a highly conserved residue in the N-terminal diaphanous-inhibitory domain (DID). The mutation was not found in 670 control chromosomes. The same residue was mutated in another patient (C104F; 610982.0007) and in affected members of a family (C104W; 610982.0008). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
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|
|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, CYS104PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907035,
|
|
|
|
|
|
|
|
ClinVar: RCV000023850
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Caucasian/African patient from the French West Indies with CMTDIE (614455), Boyer et al. (2011) identified a heterozygous 311G-T transversion in exon 2 of the INF2 gene, resulting in a cys104-to-phe (C104F) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes. The same residue was mutated in another patient (C104R; 610982.0006) and in affected members of a family (C104W; 610982.0008). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, CYS104TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907036,
|
|
|
|
|
|
gnomAD: rs387907036,
|
|
|
|
|
|
ClinVar: RCV000023851, RCV001228020
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a Caucasian Canadian family with CMTDIE (614455) (Lemieux and Neemeh, 1967), Boyer et al. (2011) identified a heterozygous 312C-G transversion in exon 2 of the INF2 gene, resulting in a cys104-to-trp (C104W) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes. The same residue was mutated in 2 other unrelated patients with sporadic disease (C104R, 610982.0006 and C104F, 610982.0007). </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
</div>
|
|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
INF2, LEU128PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387907037,
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ClinVar: RCV000023852, RCV000235466, RCV001378421, RCV002362594
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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 Caucasian patients from Portugal and France, respectively, with CMTDIE (614455), Boyer et al. (2011) identified a heterozygous 383T-C transition in exon 2 of the INF2 gene, resulting in a leu128-to-pro (L128P) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was not found in 670 control chromosomes, and was confirmed to be de novo in 1 of the patients. </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>.0010 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</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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INF2, LEU132ARG
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<br />
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SNP: rs387907038,
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ClinVar: RCV000023853
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Caucasian French family with CMTDIE (614455), Boyer et al. (2011) identified a heterozygous 395T-C transition in exon 3 of the INF2 gene, resulting in a leu132-to-arg (L132R) substitution in a highly conserved residue in the N-terminal DID domain. The mutation was also identified in a patient with sporadic disease, but was not found in 670 control chromosomes. </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>.0011 CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE E</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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INF2, 9-BP DEL, NT490
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<br />
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SNP: rs1555373599,
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ClinVar: RCV000543208, RCV002286575
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of 2 Caucasian families with CMTDIE (614455), Boyer et al. (2011) identified a heterozygous 9-bp deletion (490_498del) in exon 3 of the INF2 gene, resulting in an in-frame deletion of 3 conserved residues (ala164-asp166). The mutation was not found in 670 control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Bindschadler, M., McGrath, J. L.
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<strong>Formin' new ideas about actin filament generation.</strong>
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Proc. Nat. Acad. Sci. 101: 14685-14686, 2004.
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[PubMed: 15466701]
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[Full Text: https://doi.org/10.1073/pnas.0406317101]
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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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Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., Cong, E. H., Arrondel, C., Tete, M.-J., Montjean, R., Richard, L., Karras, A., and 21 others.
|
|
<strong>INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.</strong>
|
|
New Eng. J. Med. 365: 2377-2388, 2011.
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[PubMed: 22187985]
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[Full Text: https://doi.org/10.1056/NEJMoa1109122]
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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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Brown, E. J., Schlondorff, J. S., Becker, D. J., Tsukaguchi, H., Uscinski, A. L., Higgs, H. N., Henderson, J. M., Pollak, M. R., Tonna, S. J.
|
|
<strong>Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis.</strong>
|
|
Nature Genet. 42: 72-76, 2010. Note: Erratum: Nature Genet. 42: 361 only, 2010.
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[PubMed: 20023659]
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[Full Text: https://doi.org/10.1038/ng.505]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chhabra, E. S., Higgs, H. N.
|
|
<strong>INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization.</strong>
|
|
J. Biol. Chem. 281: 26754-26767, 2006.
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[PubMed: 16818491]
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[Full Text: https://doi.org/10.1074/jbc.M604666200]
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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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Gross, M. B.
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|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 1/3/2025.
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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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|
Higgs, H. N., Peterson, K. J.
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<strong>Phylogenetic analysis of the formin homology 2 domain.</strong>
|
|
Molec. Biol. Cell 16: 1-13, 2005.
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|
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[PubMed: 15509653]
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[Full Text: https://doi.org/10.1091/mbc.e04-07-0565]
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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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Korobova, F., Ramabhadran, V., Higgs, H. N.
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<strong>An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2.</strong>
|
|
Science 339: 464-467, 2013.
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|
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|
|
[PubMed: 23349293]
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[Full Text: https://doi.org/10.1126/science.1228360]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Lemieux, G., Neemeh, J. A.
|
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<strong>Charcot-Marie-Tooth disease and nephritis.</strong>
|
|
Canad. Med. Assoc. J. 97: 1193-1198, 1967.
|
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[PubMed: 6054293]
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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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Subramanian, B., Williams, S., Karp, S., Hennino, M. F., Jacas, S., Lee, M., Riella, C. V., Alper, S. L., Higgs, H. N., Pollak, M. R.
|
|
<strong>INF2 mutations cause kidney disease through a gain-of-function mechanism.</strong>
|
|
Sci. Adv. 10: eadr1017, 2024.
|
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|
|
[PubMed: 39536114]
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[Full Text: https://doi.org/10.1126/sciadv.adr1017]
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</p>
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</li>
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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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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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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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Matthew B. Gross - updated : 01/03/2025<br>Bao Lige - updated : 01/03/2025<br>Ada Hamosh - updated : 2/21/2013<br>Cassandra L. Kniffin - updated : 1/30/2012<br>Marla J. F. O'Neill - updated : 1/29/2010<br>Matthew B. Gross - updated : 4/26/2007
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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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<br />
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Creation Date:
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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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Alan F. Scott : 4/26/2007
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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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mgross : 01/03/2025<br>mgross : 01/03/2025<br>carol : 03/11/2015<br>alopez : 2/26/2013<br>terry : 2/21/2013<br>terry : 1/29/2013<br>alopez : 3/22/2012<br>carol : 1/30/2012<br>ckniffin : 1/30/2012<br>mgross : 5/17/2010<br>alopez : 1/29/2010<br>alopez : 1/29/2010<br>mgross : 4/26/2007
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