3531 lines
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3531 lines
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- *606622 - SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY A-LIKE PROTEIN 1; SMARCAL1
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<p>
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<span class="h4">*606622</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606622">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000138375;t=ENST00000357276" 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=50485" 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=606622" 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=ENSG00000138375;t=ENST00000357276" 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_001127207,NM_014140" 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_014140" 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=606622" 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=05969&isoform_id=05969_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/SMARCAL1" 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/6102878,6693791,7019996,7861961,16741295,18463933,21071060,27696616,60390962,62702171,119590973,187761314" 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/Q9NZC9" 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=50485" 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=ENSG00000138375;t=ENST00000357276" 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=SMARCAL1" 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=SMARCAL1" 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+50485" 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/SMARCAL1" 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:50485" 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/50485" 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=chr2&hgg_gene=ENST00000357276.9&hgg_start=216412484&hgg_end=216483053&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:11102" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/smarcal1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606622[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 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=606622[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000138375" 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=SMARCAL1" 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=SMARCAL1" 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=SMARCAL1" 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="http://structure.bmc.lu.se/idbase/SMARCAL1base/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SMARCAL1&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/PA35952" 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:11102" 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/FBgn0031655.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:1859183" 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/SMARCAL1#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:1859183" 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/50485/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=50485" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00015806;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041210-303" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SMARCAL1&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> 723995003<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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606622
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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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SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY A-LIKE PROTEIN 1; SMARCAL1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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SMARCA-LIKE PROTEIN 1<br />
|
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HepA-RELATED PROTEIN; HARP
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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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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SMARCAL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SMARCAL1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/990?start=-3&limit=10&highlight=990">2q35</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:216412484-216483053&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'})">2:216,412,484-216,483,053</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
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<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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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/2/990?start=-3&limit=10&highlight=990">
|
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2q35
|
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</a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Schimke immunoosseous dysplasia
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/242900"> 242900 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/606622" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606622" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<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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</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="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<p>Several multiprotein complexes are involved in the remodeling of chromatin to change nucleosome compaction for gene regulation, replication, recombination, and DNA repair. The complexes typically contain a member of the well-conserved SNF2 family of proteins (see SMARCA2; <a href="/entry/600014">600014</a>). All SNF2 family proteins contain the approximately 400-amino acid SNF2 domain, which has 7 motifs that are similar to motifs found in helicases. The SNF2 domain contains a nucleotide-binding site, a phosphate-binding loop (also called Walker A and B boxes), a DEAD box, and DNA- and ATP-binding motifs. By searching an EST database for sequences similar to the SNF2 domain, followed by RT-PCR, <a href="#4" class="mim-tip-reference" title="Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W. <strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong> Genomics 65: 274-282, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10857751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10857751</a>] [<a href="https://doi.org/10.1006/geno.2000.6174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10857751">Coleman et al. (2000)</a> obtained a cDNA encoding SMARCAL1, which they termed HARP. The predicted 954-amino acid SMARCAL1 protein, which is 72% identical to its mouse homolog, has a conserved C-terminal SNF2 domain. Northern blot analysis revealed expression of a 3.4-kb SMARCAL1 transcript in all tissues tested, with elevated levels in testis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10857751" 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 in situ hybridization and immunohistochemical analysis of mice staged from embryonic day 7.5 to postnatal day 7, <a href="#6" class="mim-tip-reference" title="Elizondo, L. I., Huang, C., Northrop, J. L., Deguchi, K., Clewing, J. M., Armstrong, D. L., Boerkoel, C. F. <strong>Schimke immuno-osseous dysplasia: a cell autonomous disorder?</strong> Am. J. Med. Genet. 140A: 340-348, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16419127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16419127</a>] [<a href="https://doi.org/10.1002/ajmg.a.31089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16419127">Elizondo et al. (2006)</a> found that Smarcal1 mRNA and protein were expressed throughout development and in all tissues that are affected in patients with Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>) such as bone, kidney, thymus, thyroid, tooth, bone marrow, hair, eye, and blood vessels. Smarcal1 was also expressed in tissues not reported to be affected in SIOD, including high expression in neural tissue such as brain, sympathetic trunk, spinal cord, and dorsal root ganglia, and expression in developing heart, skeletal muscle, pancreas, germ cells, testes, and ovaries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16419127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W. <strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong> Genomics 65: 274-282, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10857751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10857751</a>] [<a href="https://doi.org/10.1006/geno.2000.6174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10857751">Coleman et al. (2000)</a> found that the mouse Smarcal1 protein lacking its N-terminal 107 amino acids showed DNA-dependent ATPase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10857751" 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 in vitro analysis of purified human HARP, <a href="#9" class="mim-tip-reference" title="Yusufzai, T., Kadonaga, J. T. <strong>HARP is an ATP-driven annealing helicase.</strong> Science 322: 748-750, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18974355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18974355</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18974355[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.1161233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18974355">Yusufzai and Kadonaga (2008)</a> showed that HARP bound with higher affinity to forked DNA than to single-stranded DNA (sDNA) or double-stranded DNA (dsDNA). HARP had ATPase activity that was stimulated by forked DNA, and to a lesser extent by ssDNA and dsDNA. HARP did not show detectable helicase activity, but it showed ATP-dependent annealing helicase activity toward replication protein A (RPA; see <a href="/entry/179835">179835</a>)-unwound DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18974355" 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="#8" class="mim-tip-reference" title="Yuan, J., Ghosal, G., Chen, J. <strong>The annealing helicase HARP protects stalled replication forks.</strong> Genes Dev. 23: 2394-2399, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793864[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/10.1101/gad.1836409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19793864">Yuan et al. (2009)</a> showed that the N-terminal 28 amino acids of HARP bound domain A of RPA1, and that HARP was recruited to stalled replication forks via its direct interaction with RPA1. HARP did not affect binding of RPA1 to ssDNA. Depletion of HARP increased spontaneous DNA damage and G2/M arrest. <a href="#8" class="mim-tip-reference" title="Yuan, J., Ghosal, G., Chen, J. <strong>The annealing helicase HARP protects stalled replication forks.</strong> Genes Dev. 23: 2394-2399, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793864[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/10.1101/gad.1836409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19793864">Yuan et al. (2009)</a> hypothesized that HARP stabilizes stalled replication forks during cell proliferation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19793864" 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>Independently, <a href="#10" class="mim-tip-reference" title="Yusufzai, T., Kong, X., Yokomori, K., Kadonaga, J. T. <strong>The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA.</strong> Genes Dev. 23: 2400-2404, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793863[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/10.1101/gad.1831509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19793863">Yusufzai et al. (2009)</a> found that HARP bound RPA via a conserved N-terminal motif and was recruited to sites of DNA repair in HeLa cells. They proposed that the interaction of HARP with RPA increases the concentration of annealing helicase activity in the vicinity of ssDNA regions for the regeneration of dsDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19793863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bansbach, C. E., Betous, R., Lovejoy, C. A., Glick, G. G., Cortez, D. <strong>The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks.</strong> Genes Dev. 23: 2405-2414, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793861</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793861[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/10.1101/gad.1839909" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19793861">Bansbach et al. (2009)</a> found that an N-terminal motif of SMARCAL1 interacted with RPA32 (RPA2; <a href="/entry/179836">179836</a>) and that this interaction recruited SMARCAL1 to stalled replication forks. SMARCAL1 was phosphorylated by ATM (<a href="/entry/607585">607585</a>), ATR (<a href="/entry/601215">601215</a>), and DNAPK (PRKDC; <a href="/entry/600899">600899</a>) in response to replication-associated DNA damage. Loss of SMARCAL1 function caused persistent RPA phosphorylation, RPA loading onto chromatin, and hypersensitivity to replication stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19793861" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By comparison of cDNA and genomic sequences, <a href="#4" class="mim-tip-reference" title="Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W. <strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong> Genomics 65: 274-282, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10857751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10857751</a>] [<a href="https://doi.org/10.1006/geno.2000.6174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10857751">Coleman et al. (2000)</a> determined that both the mouse and human SMARCAL1 genes contain 17 exons that range in size from 37 to 869 bp. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10857751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using in silico analysis, <a href="#4" class="mim-tip-reference" title="Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W. <strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong> Genomics 65: 274-282, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10857751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10857751</a>] [<a href="https://doi.org/10.1006/geno.2000.6174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10857751">Coleman et al. (2000)</a> mapped the SMARCAL1 gene to chromosome 2q34-q36. They mapped the mouse gene to chromosome 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10857751" 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>Schimke immunoosseous dysplasia is an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. Using genomewide linkage mapping and a positional candidate approach, <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> determined that mutations in SMARCAL1 are responsible for SIOD. Through analysis of data from persons with this disorder in 26 unrelated families, they observed that affected individuals from 13 of 23 families with severe disease had 2 alleles with nonsense, frameshift, or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicated that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" 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="#3" class="mim-tip-reference" title="Clewing, J. M., Fryssira, H., Goodman, D., Smithson, S. F., Sloan, E. A., Lou, S., Huang, Y., Choi, K., Lucke, T., Alpay, H., Andre, J.-L., Asakura, Y., and 49 others. <strong>Schimke immunoosseous dysplasia: suggestions of genetic diversity.</strong> Hum. Mutat. 28: 273-283, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17089404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17089404</a>] [<a href="https://doi.org/10.1002/humu.20432" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17089404">Clewing et al. (2007)</a> stated that 43 different mutations in the SMARCAL1 gene had been identified. In 4 SIOD patients with a presumed monoallelic, heterozygous mutation in the SMARCAL1 gene, the authors did not find expressed RNA and/or protein from the other allele, thus demonstrating that these 4 patients had biallelic SMARCAL1 mutations, though the second mutation could not be identified by conventional assays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17089404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Yusufzai, T., Kadonaga, J. T. <strong>HARP is an ATP-driven annealing helicase.</strong> Science 322: 748-750, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18974355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18974355</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18974355[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.1161233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18974355">Yusufzai and Kadonaga (2008)</a> found that 2 mutations in HARP, R764Q (<a href="#0008">606622.0008</a>) and R586W (<a href="#0006">606622.0006</a>), which are associated with severe and mild SIOD, respectively, did not affect DNA-binding activity of HARP. However, they reduced or eliminated the ATPase and annealing helicase activities of HARP in a manner that correlated with disease severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18974355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F. <strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong> J. Med. Genet. 46: 49-59, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18805831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18805831</a>] [<a href="https://doi.org/10.1136/jmg.2008.060095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18805831">Elizondo et al. (2009)</a> characterized the effects of various SIOD-associated SMARCAL1 mutations, including E848X (<a href="#0001">606622.0001</a>) and R586W, in patient tissues and cell lines, and observed that the mutations affected protein expression, stability, subcellular localization, chromatin binding, and enzymatic activity. The authors scored the severity of disease in 15 SIOD patients and found that all patients with milder disease expressed at least 1 SMARCAL1 allele encoding a protein product localizing within the nucleus; however, no other observations were predictive of the phenotypic features or disease course. Expressing SMARCAL1 missense mutants in Drosophila melanogaster showed that disease severity was inversely proportional to overall SMARCAL1 activity. <a href="#5" class="mim-tip-reference" title="Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F. <strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong> J. Med. Genet. 46: 49-59, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18805831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18805831</a>] [<a href="https://doi.org/10.1136/jmg.2008.060095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18805831">Elizondo et al. (2009)</a> stated that their results showed for the first time that SMARCAL1 binds chromatin in vivo, and that SIOD arises from impairment of diverse SMARCAL1 functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18805831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>8 Selected Examples</a>):</strong>
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<a href="/allelicVariants/606622" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606622[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<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> rs119473033 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473033;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/rs119473033?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=rs119473033" 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=rs119473033" 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=RCV000004388 OR RCV000415311 OR RCV001849255 OR RCV002472924" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004388, RCV000415311, RCV001849255, RCV002472924" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004388...</a>
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<p>In affected members of 2 families with Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>), <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> found homozygosity for a glu848-to-ter (E848X) nonsense mutation in the SMARCAL1 gene. The same E848X mutation in compound heterozygous state was found with different missense mutations in 2 other families, and with a frameshift mutation in 1 family. The disorder was severe in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F. <strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong> J. Med. Genet. 46: 49-59, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18805831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18805831</a>] [<a href="https://doi.org/10.1136/jmg.2008.060095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18805831">Elizondo et al. (2009)</a> analyzed the effects of the E848X mutation in patient tissues and cell lines and found that SMARCAL1 mRNA encoding E848X was expressed at near-normal levels, suggesting that the nonsense mutation is too close to the C-terminal tail to induce nonsense-mediated RNA decay. However, protein levels were nearly undetectable, and the prominent cytoplasmic localization of the mutant protein despite intact nuclear localization signals suggested that the C-terminal region is necessary for protein stability. Consistent with the idea of the protein being improperly folded, the E848X mutant hydrolyzed ATP about half as well as wildtype SMARCAL1 in the presence of hairpin DNA, which also indicated that ATPase activity is insufficient for nuclear retention of SMARCAL1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18805831" 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> rs119473034 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473034;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/rs119473034?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=rs119473034" 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=rs119473034" 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=RCV000004389" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004389" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004389</a>
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<p>In a proband with Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>), <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> found compound heterozygosity for 2 nonsense mutations in the SMARCAL1 gene: arg17 to ter (R17X) and gln34 to ter (Q34X; <a href="#0003">606622.0003</a>). The disorder was severe in this case. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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">rs119473035 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473035;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=rs119473035" 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=rs119473035" 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=RCV000004390" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004390" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004390</a>
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<p>For discussion of the gln34-to-ter (Q34X) mutation in the SMARCAL1 gene that was identified in compound heterozygous state in a patient with Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>) by <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a>, see <a href="#0002">606622.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" 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">rs119473036 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473036;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=rs119473036" 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=rs119473036" 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=RCV000004391" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004391" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004391</a>
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<p>In a proband with relatively mild Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>), <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> found compound heterozygosity for 2 missense mutations in the SMARCAL1 gene: ile548 to asn (I548N) and arg645 to cys (R645C; <a href="#0005">606622.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" 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>.0005 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs119473037 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473037;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/rs119473037?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=rs119473037" 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=rs119473037" 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=RCV000004392" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004392" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004392</a>
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<p>For discussion of the arg645-to-cys (R645C) mutation in the SMARCAL1 gene that was found in compound heterozygous state in a patient with relatively mild Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>) by <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a>, see <a href="#0004">606622.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" 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 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs119473038 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119473038;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/rs119473038?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=rs119473038" 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=rs119473038" 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=RCV000004393 OR RCV001849256" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004393, RCV001849256" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004393...</a>
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<p>In a proband with relatively mild Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>), <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> found homozygosity for an arg586-to-trp (R586W) missense mutation in the SMARCAL1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Yusufzai, T., Kadonaga, J. T. <strong>HARP is an ATP-driven annealing helicase.</strong> Science 322: 748-750, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18974355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18974355</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18974355[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.1161233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18974355">Yusufzai and Kadonaga (2008)</a> showed that the R586W mutation reduced the ATPase activity of HARP and the annealing helicase activity of HARP with a partially unwound DNA substrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18974355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F. <strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong> J. Med. Genet. 46: 49-59, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18805831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18805831</a>] [<a href="https://doi.org/10.1136/jmg.2008.060095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18805831">Elizondo et al. (2009)</a> analyzed the effects of the R586W mutation in patient tissues and cell lines and observed SMARCAL1 mRNA and protein expression, albeit with lower steady-state levels than seen with wildtype SMARCAL1. In T-Rex-293 cell lines, R586W showed minimal DNA-dependent ATP hydrolysis compared to wildtype, but had complete nuclear localization, indicating that ATPase activity is not necessary for nuclear retention of SMARCAL1. In contrast to the diffuse nuclear staining observed with wildtype, however, the R586W mutant localized to or aggregated within discrete nuclear domains. Studies in Drosophila melanogaster showed diminished staining of the polytene chromosomes compared to wildtype, suggesting that the mutant binds chromatin less efficiently in vivo than wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18805831" 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>.0007 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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">rs1574450161 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1574450161;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=rs1574450161" 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=rs1574450161" 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=RCV001027619 OR RCV001862410" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001027619, RCV001862410" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001027619...</a>
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<p><a href="#7" class="mim-tip-reference" title="Taha, D., Boerkoel, C. F., Balfe, J. W., Khalifah, M., Sloan, E. A., Barbar, M., Haider, A., Kanaan, H. <strong>Fatal lymphoproliferative disorder in a child with Schimke immuno-osseous dysplasia.</strong> Am. J. Med. Genet. 131A: 194-199, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523612</a>] [<a href="https://doi.org/10.1002/ajmg.a.30356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15523612">Taha et al. (2004)</a> reported a patient with Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>) who was homozygous for a 4-bp deletion that removed 2 nucleotides from the 3-prime end of exon 6 of the SMARCAL1 gene, and 2 nucleotides from the beginning of intron 6 (1146-1147delAA+IVS6+2delGT). The mutation effectively destroyed the splice donor site and resulted in a null allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs267607071 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607071;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/rs267607071?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=rs267607071" 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=rs267607071" 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=RCV000004395" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004395" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004395</a>
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<p>In a family with severe Schimke immunoosseous dysplasia (SIOD; <a href="/entry/242900">242900</a>), <a href="#2" class="mim-tip-reference" title="Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others. <strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong> Nature Genet. 30: 215-220, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>] [<a href="https://doi.org/10.1038/ng821" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799392">Boerkoel et al. (2002)</a> identified compound heterozygosity for mutations in the SMARCAL1 gene. The maternal allele had an arg744-to-gln (R764Q) mutation that affected a conserved arginine. The paternal allele had a glu848-to-ter (E848X; <a href="#0001">606622.0001</a>) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Yusufzai, T., Kadonaga, J. T. <strong>HARP is an ATP-driven annealing helicase.</strong> Science 322: 748-750, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18974355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18974355</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18974355[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.1161233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18974355">Yusufzai and Kadonaga (2008)</a> showed that the R764Q mutation eliminated the ATPase activity of HARP as well as the annealing helicase activity of HARP against a partially unwound DNA substrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18974355" 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="#8" class="mim-tip-reference" title="Yuan, J., Ghosal, G., Chen, J. <strong>The annealing helicase HARP protects stalled replication forks.</strong> Genes Dev. 23: 2394-2399, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793864[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/10.1101/gad.1836409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19793864">Yuan et al. (2009)</a> noted that the R764Q mutation is located within the conserved ATPase domain of HARP. They found that expression of HARP with the R764Q mutation could not restore cell cycle progression or suppress spontaneous DNA damage in cells depleted of wildtype HARP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19793864" 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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Bansbach, C. E., Betous, R., Lovejoy, C. A., Glick, G. G., Cortez, D.
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<strong>The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks.</strong>
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Genes Dev. 23: 2405-2414, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793861</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793861[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=19793861" 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/10.1101/gad.1839909" target="_blank">Full Text</a>]
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Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others.
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<strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong>
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Nature Genet. 30: 215-220, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799392" 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/ng821" target="_blank">Full Text</a>]
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Clewing, J. M., Fryssira, H., Goodman, D., Smithson, S. F., Sloan, E. A., Lou, S., Huang, Y., Choi, K., Lucke, T., Alpay, H., Andre, J.-L., Asakura, Y., and 49 others.
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<strong>Schimke immunoosseous dysplasia: suggestions of genetic diversity.</strong>
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Hum. Mutat. 28: 273-283, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17089404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17089404</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17089404" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20432" target="_blank">Full Text</a>]
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Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W.
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<strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong>
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Genomics 65: 274-282, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10857751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10857751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10857751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.2000.6174" target="_blank">Full Text</a>]
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Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F.
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<strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong>
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J. Med. Genet. 46: 49-59, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18805831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18805831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18805831" 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/10.1136/jmg.2008.060095" target="_blank">Full Text</a>]
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Elizondo, L. I., Huang, C., Northrop, J. L., Deguchi, K., Clewing, J. M., Armstrong, D. L., Boerkoel, C. F.
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<strong>Schimke immuno-osseous dysplasia: a cell autonomous disorder?</strong>
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Am. J. Med. Genet. 140A: 340-348, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16419127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16419127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16419127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.31089" target="_blank">Full Text</a>]
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Taha, D., Boerkoel, C. F., Balfe, J. W., Khalifah, M., Sloan, E. A., Barbar, M., Haider, A., Kanaan, H.
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<strong>Fatal lymphoproliferative disorder in a child with Schimke immuno-osseous dysplasia.</strong>
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Am. J. Med. Genet. 131A: 194-199, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15523612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15523612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15523612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30356" target="_blank">Full Text</a>]
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Yuan, J., Ghosal, G., Chen, J.
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<strong>The annealing helicase HARP protects stalled replication forks.</strong>
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Genes Dev. 23: 2394-2399, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793864[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=19793864" 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/10.1101/gad.1836409" target="_blank">Full Text</a>]
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Yusufzai, T., Kadonaga, J. T.
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<strong>HARP is an ATP-driven annealing helicase.</strong>
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Science 322: 748-750, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18974355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18974355</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18974355[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=18974355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1161233" target="_blank">Full Text</a>]
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Yusufzai, T., Kong, X., Yokomori, K., Kadonaga, J. T.
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<strong>The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA.</strong>
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Genes Dev. 23: 2400-2404, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19793863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19793863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19793863[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=19793863" 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/10.1101/gad.1831509" target="_blank">Full Text</a>]
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Patricia A. Hartz - updated : 12/17/2009
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Marla J. F. O'Neill - updated : 5/15/2009<br>Cassandra L. Kniffin - updated : 5/16/2007<br>Marla J. F. O'Neill - updated : 3/7/2006<br>Victor A. McKusick - updated : 1/22/2002
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Paul J. Converse : 1/18/2002
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/30/2014<br>mgross : 1/6/2010<br>mgross : 1/4/2010<br>terry : 12/17/2009<br>wwang : 6/1/2009<br>terry : 5/15/2009<br>terry : 5/15/2009<br>wwang : 5/22/2007<br>ckniffin : 5/16/2007<br>ckniffin : 5/16/2007<br>wwang : 3/15/2006<br>terry : 3/7/2006<br>terry : 3/7/2006<br>wwang : 1/27/2005<br>wwang : 1/26/2005<br>alopez : 1/23/2002<br>terry : 1/22/2002<br>mgross : 1/18/2002
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606622
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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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SWI/SNF-RELATED, MATRIX-ASSOCIATED, ACTIN-DEPENDENT REGULATOR OF CHROMATIN, SUBFAMILY A-LIKE PROTEIN 1; SMARCAL1
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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SMARCA-LIKE PROTEIN 1<br />
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HepA-RELATED PROTEIN; HARP
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</span>
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</h4>
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</div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SMARCAL1</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> 723995003;
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</span>
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</p>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 2q35
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:216,412,484-216,483,053 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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2q35
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</span>
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</td>
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<td>
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<span class="mim-font">
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Schimke immunoosseous dysplasia
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</span>
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</td>
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<td>
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<span class="mim-font">
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242900
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Several multiprotein complexes are involved in the remodeling of chromatin to change nucleosome compaction for gene regulation, replication, recombination, and DNA repair. The complexes typically contain a member of the well-conserved SNF2 family of proteins (see SMARCA2; 600014). All SNF2 family proteins contain the approximately 400-amino acid SNF2 domain, which has 7 motifs that are similar to motifs found in helicases. The SNF2 domain contains a nucleotide-binding site, a phosphate-binding loop (also called Walker A and B boxes), a DEAD box, and DNA- and ATP-binding motifs. By searching an EST database for sequences similar to the SNF2 domain, followed by RT-PCR, Coleman et al. (2000) obtained a cDNA encoding SMARCAL1, which they termed HARP. The predicted 954-amino acid SMARCAL1 protein, which is 72% identical to its mouse homolog, has a conserved C-terminal SNF2 domain. Northern blot analysis revealed expression of a 3.4-kb SMARCAL1 transcript in all tissues tested, with elevated levels in testis. </p><p>By in situ hybridization and immunohistochemical analysis of mice staged from embryonic day 7.5 to postnatal day 7, Elizondo et al. (2006) found that Smarcal1 mRNA and protein were expressed throughout development and in all tissues that are affected in patients with Schimke immunoosseous dysplasia (SIOD; 242900) such as bone, kidney, thymus, thyroid, tooth, bone marrow, hair, eye, and blood vessels. Smarcal1 was also expressed in tissues not reported to be affected in SIOD, including high expression in neural tissue such as brain, sympathetic trunk, spinal cord, and dorsal root ganglia, and expression in developing heart, skeletal muscle, pancreas, germ cells, testes, and ovaries. </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>Coleman et al. (2000) found that the mouse Smarcal1 protein lacking its N-terminal 107 amino acids showed DNA-dependent ATPase activity. </p><p>By in vitro analysis of purified human HARP, Yusufzai and Kadonaga (2008) showed that HARP bound with higher affinity to forked DNA than to single-stranded DNA (sDNA) or double-stranded DNA (dsDNA). HARP had ATPase activity that was stimulated by forked DNA, and to a lesser extent by ssDNA and dsDNA. HARP did not show detectable helicase activity, but it showed ATP-dependent annealing helicase activity toward replication protein A (RPA; see 179835)-unwound DNA. </p><p>Yuan et al. (2009) showed that the N-terminal 28 amino acids of HARP bound domain A of RPA1, and that HARP was recruited to stalled replication forks via its direct interaction with RPA1. HARP did not affect binding of RPA1 to ssDNA. Depletion of HARP increased spontaneous DNA damage and G2/M arrest. Yuan et al. (2009) hypothesized that HARP stabilizes stalled replication forks during cell proliferation. </p><p>Independently, Yusufzai et al. (2009) found that HARP bound RPA via a conserved N-terminal motif and was recruited to sites of DNA repair in HeLa cells. They proposed that the interaction of HARP with RPA increases the concentration of annealing helicase activity in the vicinity of ssDNA regions for the regeneration of dsDNA. </p><p>Bansbach et al. (2009) found that an N-terminal motif of SMARCAL1 interacted with RPA32 (RPA2; 179836) and that this interaction recruited SMARCAL1 to stalled replication forks. SMARCAL1 was phosphorylated by ATM (607585), ATR (601215), and DNAPK (PRKDC; 600899) in response to replication-associated DNA damage. Loss of SMARCAL1 function caused persistent RPA phosphorylation, RPA loading onto chromatin, and hypersensitivity to replication stress. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By comparison of cDNA and genomic sequences, Coleman et al. (2000) determined that both the mouse and human SMARCAL1 genes contain 17 exons that range in size from 37 to 869 bp. </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>Using in silico analysis, Coleman et al. (2000) mapped the SMARCAL1 gene to chromosome 2q34-q36. They mapped the mouse gene to chromosome 1. </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>Schimke immunoosseous dysplasia is an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. Using genomewide linkage mapping and a positional candidate approach, Boerkoel et al. (2002) determined that mutations in SMARCAL1 are responsible for SIOD. Through analysis of data from persons with this disorder in 26 unrelated families, they observed that affected individuals from 13 of 23 families with severe disease had 2 alleles with nonsense, frameshift, or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicated that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease. </p><p>Clewing et al. (2007) stated that 43 different mutations in the SMARCAL1 gene had been identified. In 4 SIOD patients with a presumed monoallelic, heterozygous mutation in the SMARCAL1 gene, the authors did not find expressed RNA and/or protein from the other allele, thus demonstrating that these 4 patients had biallelic SMARCAL1 mutations, though the second mutation could not be identified by conventional assays. </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>Genotype/Phenotype Correlations</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>Yusufzai and Kadonaga (2008) found that 2 mutations in HARP, R764Q (606622.0008) and R586W (606622.0006), which are associated with severe and mild SIOD, respectively, did not affect DNA-binding activity of HARP. However, they reduced or eliminated the ATPase and annealing helicase activities of HARP in a manner that correlated with disease severity. </p><p>Elizondo et al. (2009) characterized the effects of various SIOD-associated SMARCAL1 mutations, including E848X (606622.0001) and R586W, in patient tissues and cell lines, and observed that the mutations affected protein expression, stability, subcellular localization, chromatin binding, and enzymatic activity. The authors scored the severity of disease in 15 SIOD patients and found that all patients with milder disease expressed at least 1 SMARCAL1 allele encoding a protein product localizing within the nucleus; however, no other observations were predictive of the phenotypic features or disease course. Expressing SMARCAL1 missense mutants in Drosophila melanogaster showed that disease severity was inversely proportional to overall SMARCAL1 activity. Elizondo et al. (2009) stated that their results showed for the first time that SMARCAL1 binds chromatin in vivo, and that SIOD arises from impairment of diverse SMARCAL1 functions. </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>8 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 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, GLU848TER
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<br />
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SNP: rs119473033,
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gnomAD: rs119473033,
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ClinVar: RCV000004388, RCV000415311, RCV001849255, RCV002472924
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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 families with Schimke immunoosseous dysplasia (SIOD; 242900), Boerkoel et al. (2002) found homozygosity for a glu848-to-ter (E848X) nonsense mutation in the SMARCAL1 gene. The same E848X mutation in compound heterozygous state was found with different missense mutations in 2 other families, and with a frameshift mutation in 1 family. The disorder was severe in these families. </p><p>Elizondo et al. (2009) analyzed the effects of the E848X mutation in patient tissues and cell lines and found that SMARCAL1 mRNA encoding E848X was expressed at near-normal levels, suggesting that the nonsense mutation is too close to the C-terminal tail to induce nonsense-mediated RNA decay. However, protein levels were nearly undetectable, and the prominent cytoplasmic localization of the mutant protein despite intact nuclear localization signals suggested that the C-terminal region is necessary for protein stability. Consistent with the idea of the protein being improperly folded, the E848X mutant hydrolyzed ATP about half as well as wildtype SMARCAL1 in the presence of hairpin DNA, which also indicated that ATPase activity is insufficient for nuclear retention of SMARCAL1. </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>.0002 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, ARG17TER
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<br />
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SNP: rs119473034,
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gnomAD: rs119473034,
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ClinVar: RCV000004389
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a proband with Schimke immunoosseous dysplasia (SIOD; 242900), Boerkoel et al. (2002) found compound heterozygosity for 2 nonsense mutations in the SMARCAL1 gene: arg17 to ter (R17X) and gln34 to ter (Q34X; 606622.0003). The disorder was severe in this case. </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>.0003 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, GLN34TER
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<br />
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SNP: rs119473035,
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ClinVar: RCV000004390
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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>For discussion of the gln34-to-ter (Q34X) mutation in the SMARCAL1 gene that was identified in compound heterozygous state in a patient with Schimke immunoosseous dysplasia (SIOD; 242900) by Boerkoel et al. (2002), see 606622.0002. </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>.0004 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, ILE548ASN
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<br />
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SNP: rs119473036,
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ClinVar: RCV000004391
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a proband with relatively mild Schimke immunoosseous dysplasia (SIOD; 242900), Boerkoel et al. (2002) found compound heterozygosity for 2 missense mutations in the SMARCAL1 gene: ile548 to asn (I548N) and arg645 to cys (R645C; 606622.0005). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, ARG645CYS
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<br />
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SNP: rs119473037,
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gnomAD: rs119473037,
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ClinVar: RCV000004392
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</span>
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<span class="mim-text-font">
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<p>For discussion of the arg645-to-cys (R645C) mutation in the SMARCAL1 gene that was found in compound heterozygous state in a patient with relatively mild Schimke immunoosseous dysplasia (SIOD; 242900) by Boerkoel et al. (2002), see 606622.0004. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, ARG586TRP
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<br />
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SNP: rs119473038,
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gnomAD: rs119473038,
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ClinVar: RCV000004393, RCV001849256
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</span>
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<span class="mim-text-font">
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<p>In a proband with relatively mild Schimke immunoosseous dysplasia (SIOD; 242900), Boerkoel et al. (2002) found homozygosity for an arg586-to-trp (R586W) missense mutation in the SMARCAL1 gene. </p><p>Yusufzai and Kadonaga (2008) showed that the R586W mutation reduced the ATPase activity of HARP and the annealing helicase activity of HARP with a partially unwound DNA substrate. </p><p>Elizondo et al. (2009) analyzed the effects of the R586W mutation in patient tissues and cell lines and observed SMARCAL1 mRNA and protein expression, albeit with lower steady-state levels than seen with wildtype SMARCAL1. In T-Rex-293 cell lines, R586W showed minimal DNA-dependent ATP hydrolysis compared to wildtype, but had complete nuclear localization, indicating that ATPase activity is not necessary for nuclear retention of SMARCAL1. In contrast to the diffuse nuclear staining observed with wildtype, however, the R586W mutant localized to or aggregated within discrete nuclear domains. Studies in Drosophila melanogaster showed diminished staining of the polytene chromosomes compared to wildtype, suggesting that the mutant binds chromatin less efficiently in vivo than wildtype. </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>.0007 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, 4-BP DEL, 1146AAGT
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<br />
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SNP: rs1574450161,
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ClinVar: RCV001027619, RCV001862410
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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>Taha et al. (2004) reported a patient with Schimke immunoosseous dysplasia (SIOD; 242900) who was homozygous for a 4-bp deletion that removed 2 nucleotides from the 3-prime end of exon 6 of the SMARCAL1 gene, and 2 nucleotides from the beginning of intron 6 (1146-1147delAA+IVS6+2delGT). The mutation effectively destroyed the splice donor site and resulted in a null allele. </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>.0008 SCHIMKE IMMUNOOSSEOUS DYSPLASIA</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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SMARCAL1, ARG764GLN
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<br />
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SNP: rs267607071,
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gnomAD: rs267607071,
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ClinVar: RCV000004395
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family with severe Schimke immunoosseous dysplasia (SIOD; 242900), Boerkoel et al. (2002) identified compound heterozygosity for mutations in the SMARCAL1 gene. The maternal allele had an arg744-to-gln (R764Q) mutation that affected a conserved arginine. The paternal allele had a glu848-to-ter (E848X; 606622.0001) nonsense mutation. </p><p>Yusufzai and Kadonaga (2008) showed that the R764Q mutation eliminated the ATPase activity of HARP as well as the annealing helicase activity of HARP against a partially unwound DNA substrate. </p><p>Yuan et al. (2009) noted that the R764Q mutation is located within the conserved ATPase domain of HARP. They found that expression of HARP with the R764Q mutation could not restore cell cycle progression or suppress spontaneous DNA damage in cells depleted of wildtype HARP. </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">
|
|
Bansbach, C. E., Betous, R., Lovejoy, C. A., Glick, G. G., Cortez, D.
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|
<strong>The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks.</strong>
|
|
Genes Dev. 23: 2405-2414, 2009.
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[PubMed: 19793861]
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[Full Text: https://doi.org/10.1101/gad.1839909]
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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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Boerkoel, C. F., Takashima, H., John, J., Yan, J., Stankiewicz, P., Rosenbarker, L., Andre, J.-L., Bogdanovic, R., Burguet, A., Cockfield, S., Cordeiro, I., Frund, S., and 19 others.
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|
<strong>Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.</strong>
|
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Nature Genet. 30: 215-220, 2002.
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[PubMed: 11799392]
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[Full Text: https://doi.org/10.1038/ng821]
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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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Clewing, J. M., Fryssira, H., Goodman, D., Smithson, S. F., Sloan, E. A., Lou, S., Huang, Y., Choi, K., Lucke, T., Alpay, H., Andre, J.-L., Asakura, Y., and 49 others.
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|
<strong>Schimke immunoosseous dysplasia: suggestions of genetic diversity.</strong>
|
|
Hum. Mutat. 28: 273-283, 2007.
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[PubMed: 17089404]
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[Full Text: https://doi.org/10.1002/humu.20432]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Coleman, M. A., Eisen, J. A., Mohrenweiser, H. W.
|
|
<strong>Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse.</strong>
|
|
Genomics 65: 274-282, 2000.
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[PubMed: 10857751]
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[Full Text: https://doi.org/10.1006/geno.2000.6174]
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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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Elizondo, L. I., Cho, K. S., Zhang, W., Yan, J., Huang, C., Huang, Y., Choi, K., Sloan, E. A., Deguchi, K., Lou, S., Baradaran-Heravi, A., Takashima, H., Lucke, T., Quiocho, F. A., Boerkoel, C. F.
|
|
<strong>Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.</strong>
|
|
J. Med. Genet. 46: 49-59, 2009.
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[PubMed: 18805831]
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[Full Text: https://doi.org/10.1136/jmg.2008.060095]
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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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Elizondo, L. I., Huang, C., Northrop, J. L., Deguchi, K., Clewing, J. M., Armstrong, D. L., Boerkoel, C. F.
|
|
<strong>Schimke immuno-osseous dysplasia: a cell autonomous disorder?</strong>
|
|
Am. J. Med. Genet. 140A: 340-348, 2006.
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[PubMed: 16419127]
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[Full Text: https://doi.org/10.1002/ajmg.a.31089]
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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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Taha, D., Boerkoel, C. F., Balfe, J. W., Khalifah, M., Sloan, E. A., Barbar, M., Haider, A., Kanaan, H.
|
|
<strong>Fatal lymphoproliferative disorder in a child with Schimke immuno-osseous dysplasia.</strong>
|
|
Am. J. Med. Genet. 131A: 194-199, 2004.
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[PubMed: 15523612]
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[Full Text: https://doi.org/10.1002/ajmg.a.30356]
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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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Yuan, J., Ghosal, G., Chen, J.
|
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<strong>The annealing helicase HARP protects stalled replication forks.</strong>
|
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Genes Dev. 23: 2394-2399, 2009.
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|
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[PubMed: 19793864]
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[Full Text: https://doi.org/10.1101/gad.1836409]
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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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Yusufzai, T., Kadonaga, J. T.
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<strong>HARP is an ATP-driven annealing helicase.</strong>
|
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Science 322: 748-750, 2008.
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[PubMed: 18974355]
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[Full Text: https://doi.org/10.1126/science.1161233]
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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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Yusufzai, T., Kong, X., Yokomori, K., Kadonaga, J. T.
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<strong>The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA.</strong>
|
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Genes Dev. 23: 2400-2404, 2009.
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[PubMed: 19793863]
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[Full Text: https://doi.org/10.1101/gad.1831509]
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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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Patricia A. Hartz - updated : 12/17/2009<br>Marla J. F. O'Neill - updated : 5/15/2009<br>Cassandra L. Kniffin - updated : 5/16/2007<br>Marla J. F. O'Neill - updated : 3/7/2006<br>Victor A. McKusick - updated : 1/22/2002
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