4211 lines
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Entry
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- *606754 - SAM DOMAIN- AND HD DOMAIN-CONTAINING PROTEIN 1; SAMHD1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*606754</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#evolution">Evolution</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606754">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<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=ENSG00000101347;t=ENST00000646673" 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=25939" 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=606754" 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 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=ENSG00000101347;t=ENST00000646673" 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_001363729,NM_001363733,NM_015474" 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_015474" 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=606754" 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=08418&isoform_id=08418_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/SAMHD1" 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/4886493,6942315,11610570,14042766,22209036,22257047,38016914,62087468,119596496,119596497,194385380,194388322,1392111272,1392111310,2086100332,2086100335,2086100342" 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/Q9Y3Z3" 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=25939" 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=ENSG00000101347;t=ENST00000646673" 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=SAMHD1" 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=SAMHD1" 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+25939" 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/SAMHD1" 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:25939" 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/25939" 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=chr20&hgg_gene=ENST00000646673.2&hgg_start=36889773&hgg_end=36951708&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:15925" 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/samhd1" 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=606754[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606754[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/SAMHD1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000101347" 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=SAMHD1" 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=SAMHD1" 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=SAMHD1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SAMHD1&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/PA34938" 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:15925" 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/FBgn0028380.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:1927468" 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/SAMHD1#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:1927468" 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/25939/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=25939" 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=WBGene00022673;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-090313-386" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
|
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</a>
|
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</span>
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:25939" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=SAMHD1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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606754
|
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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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SAM DOMAIN- AND HD DOMAIN-CONTAINING PROTEIN 1; SAMHD1
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DENDRITIC CELL-DERIVED IFNG-INDUCED PROTEIN; DCIP
|
|
</span>
|
|
</h4>
|
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</div>
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SAMHD1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SAMHD1</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/20/264?start=-3&limit=10&highlight=264">20q11.23</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr20:36889773-36951708&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'})">20:36,889,773-36,951,708</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
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|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=614415,612952" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/20/264?start=-3&limit=10&highlight=264">
|
|
20q11.23
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Chilblain lupus 2
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614415"> 614415 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
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|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Aicardi-Goutieres syndrome 5
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/612952"> 612952 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
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<p>SAMHD1 is a 3-prime exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. It functions as a human immunodeficiency virus (HIV)-1 (see <a href="/entry/609423">609423</a>) restriction factor by hydrolyzing dNTPs and decreasing their concentration to a level below that necessary for retroviral reverse transcription (<a href="#1" class="mim-tip-reference" title="Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulos, D., Berka, U., Lienenklaus, S., Peschke, K., Gibbert, K., Wittmann, S., Lindemann, D., Weiss, S., Dahl, A., Naumann, R., Dittmer, U., Kim, B., Mueller, W., Gramberg, T., Roers, A. <strong>Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.</strong> Cell Rep. 4: 689-696, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23972988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23972988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23972988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.celrep.2013.07.037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23972988">Behrendt et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23972988" 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>Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) able to induce a primary T-cell response in vivo. With maturation, DCs shift from antigen-uptake and -processing functions to an antigen-presentation phenotype. By screening an EST database derived from a DC cDNA library for sequences homologous to the mouse gamma-interferon (IFNG; <a href="/entry/147570">147570</a>)-induced gene Mg11, followed by RACE, <a href="#12" class="mim-tip-reference" title="Li, N., Zhang, W., Cao, X. <strong>Identification of human homologue of mouse IFN-gamma induced protein from human dendritic cells.</strong> Immun. Lett. 74: 221-224, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11064105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11064105</a>] [<a href="https://doi.org/10.1016/s0165-2478(00)00276-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11064105">Li et al. (2000)</a> obtained a cDNA encoding SAMHD1, which they termed DCIP. The deduced 626-amino acid protein, which is 72% identical to mouse Mg11, contains several phosphorylation and N-myristoylation sites, an N-glycosylation site, and an amidation site. It has no signal peptide or transmembrane region, suggesting that DCIP is an intracellular protein. RT-PCR analysis detected wide but variable expression in most cell lines tested. Northern blot analysis revealed expression of a 5.2-kb transcript in all tissues tested except brain and thymus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11064105" 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="#10" class="mim-tip-reference" title="Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., Margottin-Goguet, F. <strong>SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.</strong> Nature Immun. 13: 223-229, 2012. Note: Erratum: Nature Immun. 14: 877 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22327569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22327569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22327569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ni.2236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22327569">Lahouassa et al. (2012)</a> noted that SAMHD1 consists of an N-terminal sterile alpha motif domain and a central HD domain with putative nucleotidase and phosphodiesterase activities, respectively. They stated that dendritic cells, monocyte-derived macrophages, and HIV-1-permissive CD4 (<a href="/entry/186940">186940</a>)-positive T cells have high, moderate, and low SAMHD1 expression, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22327569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 5/8/2012."None>Gross (2012)</a> mapped the SAMHD1 gene to chromosome 20q11.23 based on an alignment of the SAMHD1 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB013847" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB013847</a>) with the genomic sequence (GRCh37).</p>
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<p>In Myd88 (<a href="/entry/602170">602170</a>)-null mice that have impaired immune response, <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> showed that transfection of macrophages with immunostimulatory DNA resulted in upregulation of Samhd1 expression. Macrophages from Myd88/Ifnar1 (<a href="/entry/107450">107450</a>) double-knockout mice showed that this expression was interferon-dependent. The findings were consistent with the hypothesis that SAMHD1 expression can be induced by type 1 interferons and suggested that SAMHD1 may also act as a negative regulator of the immunostimulatory DNA response. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" 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="Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Segeral, E., Yatim, A., Emiliani, S., Schwartz, O., Benkirane, M. <strong>SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.</strong> Nature 474: 654-657, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21613998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21613998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21613998[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21613998">Laguette et al. (2011)</a> identified SAMHD1 as the restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. SAMHD1 is a protein involved in Aicardi-Goutieres syndrome (see <a href="/entry/612952">612952</a>), a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. <a href="#9" class="mim-tip-reference" title="Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Segeral, E., Yatim, A., Emiliani, S., Schwartz, O., Benkirane, M. <strong>SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.</strong> Nature 474: 654-657, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21613998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21613998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21613998[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21613998">Laguette et al. (2011)</a> showed that Vpx, the primate lentivirus auxiliary protein, induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in nonpermissive cell lines alleviated HIV-1 restriction and was associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibited HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction was abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increased the susceptibility of monocytic-derived dendritic cells to infection. <a href="#9" class="mim-tip-reference" title="Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Segeral, E., Yatim, A., Emiliani, S., Schwartz, O., Benkirane, M. <strong>SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.</strong> Nature 474: 654-657, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21613998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21613998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21613998[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10117" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21613998">Laguette et al. (2011)</a> concluded that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21613998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., Skowronski, J. <strong>Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.</strong> Nature 474: 658-661, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21720370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21720370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21720370[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21720370">Hrecka et al. (2011)</a> independently demonstrated that the inhibition of HIV-1 infection in macrophages involves the cellular SAMHD1 protein. Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase (see <a href="/entry/617259">617259</a>), leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutieres syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. <a href="#7" class="mim-tip-reference" title="Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., Skowronski, J. <strong>Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.</strong> Nature 474: 658-661, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21720370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21720370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21720370[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21720370">Hrecka et al. (2011)</a> concluded that their findings showed that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncovered an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21720370" 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="Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G. I., Christodoulou, E., Walker, P. A., Kelly, G., Haire, L. F., Yap, M. W., de Carvalho, L. P. S., Stoye, J. P., Crow, Y. J., Taylor, I. A., Webb, M. <strong>HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.</strong> Nature 480: 379-382, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22056990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22056990</a>] [<a href="https://doi.org/10.1038/nature10623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22056990">Goldstone et al. (2011)</a> showed that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. Based on these findings and analysis of the crystal structure of the catalytic core of SAMHD1, <a href="#5" class="mim-tip-reference" title="Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G. I., Christodoulou, E., Walker, P. A., Kelly, G., Haire, L. F., Yap, M. W., de Carvalho, L. P. S., Stoye, J. P., Crow, Y. J., Taylor, I. A., Webb, M. <strong>HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.</strong> Nature 480: 379-382, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22056990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22056990</a>] [<a href="https://doi.org/10.1038/nature10623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22056990">Goldstone et al. (2011)</a> proposed that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolyzing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral cDNA synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22056990" 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 measuring intracellular dNTP pools in human myeloid cells, <a href="#10" class="mim-tip-reference" title="Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., Margottin-Goguet, F. <strong>SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.</strong> Nature Immun. 13: 223-229, 2012. Note: Erratum: Nature Immun. 14: 877 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22327569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22327569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22327569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ni.2236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22327569">Lahouassa et al. (2012)</a> found that SAMHD1 lowered the dNTP concentration to an amount that failed to support reverse transcription, thereby establishing a cellular state that was not permissive to lentiviral infection. Vpx induced degradation of SAMHD1, resulting in a large intracellular dNTP pool and restoration of permissiveness to infection. <a href="#10" class="mim-tip-reference" title="Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., Margottin-Goguet, F. <strong>SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.</strong> Nature Immun. 13: 223-229, 2012. Note: Erratum: Nature Immun. 14: 877 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22327569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22327569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22327569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ni.2236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22327569">Lahouassa et al. (2012)</a> proposed that nucleotide pool depletion may be a general mechanism for protecting cells from infectious agents that replicate through a DNA intermediate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22327569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Coquel, F., Silva, M.-J., Techer, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., Promonet, A., Cribier, A., and 9 others. <strong>SAMHD1 acts at stalled replication forks to prevent interferon induction.</strong> Nature 557: 57-61, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29670289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29670289</a>] [<a href="https://doi.org/10.1038/s41586-018-0050-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29670289">Coquel et al. (2018)</a> demonstrated that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11 (<a href="/entry/600814">600814</a>). This function activates the ATR (<a href="/entry/601215">601215</a>)-CHK1 (<a href="/entry/603078">603078</a>) checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS (<a href="/entry/613973">613973</a>)-STING (<a href="/entry/612374">612374</a>) pathway to induce expression of proinflammatory type I interferons (e.g., IFNA1, <a href="/entry/147660">147660</a>). <a href="#2" class="mim-tip-reference" title="Coquel, F., Silva, M.-J., Techer, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., Promonet, A., Cribier, A., and 9 others. <strong>SAMHD1 acts at stalled replication forks to prevent interferon induction.</strong> Nature 557: 57-61, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29670289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29670289</a>] [<a href="https://doi.org/10.1038/s41586-018-0050-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29670289">Coquel et al. (2018)</a> concluded that SAMHD1 is an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29670289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#5" class="mim-tip-reference" title="Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G. I., Christodoulou, E., Walker, P. A., Kelly, G., Haire, L. F., Yap, M. W., de Carvalho, L. P. S., Stoye, J. P., Crow, Y. J., Taylor, I. A., Webb, M. <strong>HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.</strong> Nature 480: 379-382, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22056990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22056990</a>] [<a href="https://doi.org/10.1038/nature10623" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22056990">Goldstone et al. (2011)</a> solved the crystal structure of the catalytic core of SAMHD1, which revealed that the protein is dimeric and indicated a molecular basis for dGTP stimulation of catalytic activity against dNTPs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22056990" 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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By genomewide linkage analysis and candidate gene sequencing of multiple families with Aicardi-Goutieres syndrome (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified homozygous or compound heterozygous mutations in the SAMHD1 gene (see, e.g., <a href="#0001">606754.0001</a>-<a href="#0007">606754.0007</a>). Several of the families were consanguineous. All of the mutations involved highly conserved residues, segregated with the disease, and all unaffected parents tested were heterozygous for the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Chilblain Lupus 2</em></strong></p><p>
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In a mother and son with chilblain lupus (CHBL2; <a href="/entry/614415">614415</a>), <a href="#14" class="mim-tip-reference" title="Ravenscroft, J. C., Suri, M., Rice, G. I., Szynkiewicz, M., Crow, Y. J. <strong>Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (Letter)</strong> Am. J. Med. Genet. 155A: 235-237, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204240</a>] [<a href="https://doi.org/10.1002/ajmg.a.33778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21204240">Ravenscroft et al. (2011)</a> identified a heterozygous mutation in the SAMHD1 gene (I201N; <a href="#0011">606754.0011</a>). The findings suggested that SAMHD1 is involved in innate immunity and inflammation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21204240" 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="#8" class="mim-tip-reference" title="Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Munch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., Delsuc, F., Telenti, A., Benkirane, M. <strong>Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.</strong> Cell Host Microbe 11: 205-217, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305291</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305291[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2012.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22305291">Laguette et al. (2012)</a> reiterated that while pandemic HIV-1 has no means to counteract SAMHD1 restriction, nonpandemic HIV-2 and certain simian immunodeficiency virus (SIV) strains encode the auxiliary protein Vpx that potently overcomes the block to viral replication constituted by SAMHD1 by promoting its degradation by the proteasome machinery. Evolutionary analysis by <a href="#8" class="mim-tip-reference" title="Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Munch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., Delsuc, F., Telenti, A., Benkirane, M. <strong>Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.</strong> Cell Host Microbe 11: 205-217, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305291</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305291[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2012.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22305291">Laguette et al. (2012)</a> showed that SAMHD1 experienced strong positive selection episodes during primate evolution. Identification of SAMHD1 residues under positive selection allowed mapping of the Vpx interaction domain of SAMHD1 to the C-terminal region. SAMHD1 proteins of apes, monkeys, and lemurs were all active against HIV-1, whereas Vpx degraded and antagonized SAMHD1 in a species-specific manner. <a href="#8" class="mim-tip-reference" title="Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Munch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., Delsuc, F., Telenti, A., Benkirane, M. <strong>Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.</strong> Cell Host Microbe 11: 205-217, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305291</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305291[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2012.01.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22305291">Laguette et al. (2012)</a> questioned whether the presence of Vpx represents an advantage favoring cross-species transmission and observed that Vpx appears to be dispensable for persistence and spread in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22305291" 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="#13" class="mim-tip-reference" title="Lim, E. S., Fregoso, O. I., McCoy, C. O., Matsen, F. A., Malik, H. S., Emerman, M. <strong>The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.</strong> Cell Host Microbe 11: 194-204, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22284954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22284954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22284954[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2012.01.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22284954">Lim et al. (2012)</a> noted that only 2 of 8 primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. By functional analysis, they found that multiple Vpx proteins shared the ability to degrade SAMHD1, but that this ability was often host specific. Additionally, some Vpr proteins from viruses lacking Vpx could also potently degrade SAMHD1. Evolutionary analysis showed that the ability to degrade SAMHD1 resulted from neofunctionalization of Vpr that preceded the acquisition of Vpx in primate lentiviruses. <a href="#13" class="mim-tip-reference" title="Lim, E. S., Fregoso, O. I., McCoy, C. O., Matsen, F. A., Malik, H. S., Emerman, M. <strong>The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.</strong> Cell Host Microbe 11: 194-204, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22284954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22284954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22284954[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.chom.2012.01.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22284954">Lim et al. (2012)</a> concluded that Vpr gained a new function to degrade SAMHD1 once during viral evolution, thereby initiating an evolutionary 'arms race' with SAMHD1. However, they noted that many lentiviral lineages, including the precursors of HIV-1, never acquired this function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22284954" 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 generating mice lacking Samhd1, <a href="#1" class="mim-tip-reference" title="Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulos, D., Berka, U., Lienenklaus, S., Peschke, K., Gibbert, K., Wittmann, S., Lindemann, D., Weiss, S., Dahl, A., Naumann, R., Dittmer, U., Kim, B., Mueller, W., Gramberg, T., Roers, A. <strong>Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.</strong> Cell Rep. 4: 689-696, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23972988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23972988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23972988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.celrep.2013.07.037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23972988">Behrendt et al. (2013)</a> showed that mouse Samhd1 reduced cellular dNTP concentrations and restricted retroviral reverse transcription in lymphocytes, macrophages, and dendritic cells. Absence of Samhd1 triggered Ifnb (IFNB1; <a href="/entry/147640">147640</a>)-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types. <a href="#1" class="mim-tip-reference" title="Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulos, D., Berka, U., Lienenklaus, S., Peschke, K., Gibbert, K., Wittmann, S., Lindemann, D., Weiss, S., Dahl, A., Naumann, R., Dittmer, U., Kim, B., Mueller, W., Gramberg, T., Roers, A. <strong>Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.</strong> Cell Rep. 4: 689-696, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23972988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23972988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23972988[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.celrep.2013.07.037" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23972988">Behrendt et al. (2013)</a> proposed that Samhd1-deficient mice model important features associated with pathogenic type I IFN responses involved in AGS and SLE pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23972988" 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="#15" class="mim-tip-reference" title="Rehwinkel, J., Maelfait, J., Bridgeman, A., Rigby, R., Hayward, B., Liberatore, R. A., Bieniasz, P. D., Towers, G. J., Moita, L. F., Crow, Y. J., Bonthron, D. T., Reis e Sousa, C. <strong>SAMHD1-dependent retroviral control and escape in mice.</strong> EMBO J. 32: 2454-2462, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23872947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23872947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23872947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/emboj.2013.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23872947">Rehwinkel et al. (2013)</a> generated Samhd1 -/- mice and found that they did not develop autoimmune disease, despite displaying a type I IFN signature in spleen, macrophages, and fibroblasts. Cells lacking Samhd1 had elevated dNTP levels, but the deficiency did not lead to increased infection with pseudotyped HIV-1 vectors, likely due to high concentrations of dNTPs in Samhd1 -/- cells. A mutant HIV-1 vector having a reverse transcriptase with reduced affinity for dNTPs was sensitive to Samhd1-dependent restriction in cultured cells and mice. <a href="#15" class="mim-tip-reference" title="Rehwinkel, J., Maelfait, J., Bridgeman, A., Rigby, R., Hayward, B., Liberatore, R. A., Bieniasz, P. D., Towers, G. J., Moita, L. F., Crow, Y. J., Bonthron, D. T., Reis e Sousa, C. <strong>SAMHD1-dependent retroviral control and escape in mice.</strong> EMBO J. 32: 2454-2462, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23872947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23872947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23872947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/emboj.2013.163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23872947">Rehwinkel et al. (2013)</a> concluded that SAMHD1 can restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily conserved antiviral mechanism. They suggested that HIV-1 may have evolved with a polymerase active at low dNTP concentrations to circumvent SAMHD1 restriction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23872947" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606754[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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<p>In affected members of a Hungarian family with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a homozygous 625G-A transition in exon 5 of the SAMHD1 gene, resulting in a gly209-to-ser (G209S) substitution at a highly conserved residue. The parents were third cousins. One of the patients died at age 5 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004282 OR RCV001826413 OR RCV002476923 OR RCV004700185" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004282, RCV001826413, RCV002476923, RCV004700185" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004282...</a>
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<p>In affected members of 2 unrelated families of Maltese origin with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a homozygous 433C-T transition in exon 4 of the SAMHD1 gene, resulting in arg145-to-ter (R145X) substitution at a highly conserved residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs with variable manifestations of AGS5, <a href="#4" class="mim-tip-reference" title="Dale, R. C., Gornall, H., Singh-Grewal, D., Alcausin, M., Rice, G. I., Crow, Y. J. <strong>Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.</strong> Am. J. Med. Genet. 152A: 938-942, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358604</a>] [<a href="https://doi.org/10.1002/ajmg.a.33359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358604">Dale et al. (2010)</a> identified compound heterozygosity for 2 mutations in the SAMHD1 gene: the R145X mutation and a 490C-T transition in exon 4, resulting in an arg164-to-ter (R164X; <a href="#0008">606754.0008</a>) substitution. The father was of Maltese origin, and both the father and paternal grandfather reportedly had mild skin involvement, but genetic studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a Pakistani patient with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a homozygous G-to-C transversion in intron 14 of the SAMHD1 gene (1609-1G-C), resulting in a splice site mutation and the skipping of exon 15 as well as other abnormal transcripts. The parents were related as first cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 AICARDI-GOUTIERES SYNDROME 5</strong>
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SAMHD1, GLN149TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434518 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434518;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=rs121434518" 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=rs121434518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004285" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004285" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004285</a>
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<p>In affected members of a consanguineous Indian family with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a homozygous 445C-T transition in exon 4 of the SAMHD1 gene, resulting in a gln149-to-ter (Q149X) substitution. Patient cells carrying the Q149X substitution showed localization of the mutant SAMHD1 protein to the nucleus, confirming that the derived mRNA is not subject to nonsense-mediated decay, and indicating that the first 149 amino acids of the protein are sufficient for nuclear localization. However, expression was diminished compared to wildtype and proper localization to internal nuclear structures was less clear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 AICARDI-GOUTIERES SYNDROME 5</strong>
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</h4>
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</div>
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SAMHD1, GLN548TER
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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> rs121434519 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434519;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/rs121434519?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=rs121434519" 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=rs121434519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004286 OR RCV005031386" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004286, RCV005031386" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004286...</a>
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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 French patient with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a homozygous 1642C-T transition in exon 15 of the SAMHD1 gene, resulting in a gln548-to-ter (Q548X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 AICARDI-GOUTIERES SYNDROME 5</strong>
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</span>
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</h4>
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</div>
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SAMHD1, HIS123PRO
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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> rs121434520 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434520;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/rs121434520?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=rs121434520" 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=rs121434520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004287" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004287" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004287</a>
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 French sibs with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified a compound heterozygosity for a 368A-C transversion in exon 4 of the SAMHD1 gene, resulting in a his123-to-pro (H123P) substitution, and a 760A-G transition in exon 7, resulting in a met254-to-val (M254V; <a href="#0007">606754.0007</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" 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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</span>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 AICARDI-GOUTIERES SYNDROME 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SAMHD1, MET254VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434521 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434521;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=rs121434521" 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=rs121434521" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004288" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004288" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004288</a>
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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 met254-to-val (M254V) mutation in the SAMHD1 gene that was found in compound heterozygous state in 2 sibs with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>) by <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a>, see <a href="#0006">606754.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" 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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</span>
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<div>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 AICARDI-GOUTIERES SYNDROME 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SAMHD1, ARG164TER
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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> rs267607027 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607027;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/rs267607027?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=rs267607027" 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=rs267607027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004284 OR RCV001831512 OR RCV005025003" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004284, RCV001831512, RCV005025003" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004284...</a>
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</span>
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<span class="mim-text-font">
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<p>For discussion of the arg164-to-ter (R164X) mutation in the SAMHD1 gene that was found in compound heterozygous state in 2 sibs with variable manifestations of Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>) by <a href="#4" class="mim-tip-reference" title="Dale, R. C., Gornall, H., Singh-Grewal, D., Alcausin, M., Rice, G. I., Crow, Y. J. <strong>Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.</strong> Am. J. Med. Genet. 152A: 938-942, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358604</a>] [<a href="https://doi.org/10.1002/ajmg.a.33359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20358604">Dale et al. (2010)</a>, see <a href="#0002">606754.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 AICARDI-GOUTIERES SYNDROME 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SAMHD1, 9.1-KB DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023576" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023576" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023576</a>
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<p>In a boy, born of unrelated Ashkenazi Jewish parents, with severe Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>) including mitochondrial DNA deletions, <a href="#11" class="mim-tip-reference" title="Leshinsky-Silver, E., Malinger, G., Ben-Sira, L., Kidron, D., Cohen, S., Inbar, S., Bezaleli, T., Levine, A., Vinkler, C., Lev, D., Lerman-Sagie, T. <strong>A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres syndrome associated with mtDNA deletions.</strong> Europ. J. Hum. Genet. 19: 287-292, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21102625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21102625</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21102625[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21102625">Leshinsky-Silver et al. (2011)</a> identified a homozygous 9.1-kb deletion involving the SAMHD1 gene. The deletion started upstream of the promoter, encompassed exon 1, and ended in intron 1. The deletion also included the 3-prime end of RBL1 (<a href="/entry/116957">116957</a>), which may have contributed to the severe phenotype. The parents were each heterozygous for the 9.1-kb deletion, which was not identified in 100 Ashkenazi Jewish controls. The patient presented at age 3 weeks with failure to thrive, poor growth, and lack of development. He had central hypotonia with brisk tendon reflexes and choreoathetoid movements. Brain MRI showed extensive white matter destruction, delayed myelination, hypoplasia of the corpus callosum, severe cortical atrophy, destructive lesions of the aqueductal body and pons, and pathologic lesions in the frontal lobe and basal ganglia. Blood samples showed increased serum lactate, anemia, and thrombocytosis. He had profound mental retardation, poor growth, and severe irritability, and died at age 15 months. Two subsequent pregnancies were terminated after studies showed periventricular white matter lesions and hyperechogenic foci in the basal ganglia between 28 and 34 weeks' gestation. Southern blot analysis of patient skeletal muscle and liver tissue showed multiple mitochondrial DNA deletions, which were not found in blood and fibroblasts, and there were similar findings in fetal autopsy tissues. <a href="#11" class="mim-tip-reference" title="Leshinsky-Silver, E., Malinger, G., Ben-Sira, L., Kidron, D., Cohen, S., Inbar, S., Bezaleli, T., Levine, A., Vinkler, C., Lev, D., Lerman-Sagie, T. <strong>A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres syndrome associated with mtDNA deletions.</strong> Europ. J. Hum. Genet. 19: 287-292, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21102625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21102625</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21102625[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21102625">Leshinsky-Silver et al. (2011)</a> suggested that mutant SAMHD1 causes an induction of the cell intrinsic antiviral response, apoptosis, and mitochondrial DNA destruction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21102625" 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> rs387906948 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906948;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/rs387906948?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=rs387906948" 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=rs387906948" 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=RCV000023577" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023577" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023577</a>
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<p>In a Canadian family with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>), <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a> identified compound heterozygosity for 2 mutations in the SAMHD1 gene: a 427C-T transition in exon 4, resulting in an arg143-to-cys (R143C) substitution, and a 602T-A transversion in exon 5, resulting in an ile201-to-asn (I201N; <a href="#0011">606754.0011</a>) substitution. Both mutations occurred at highly conserved residues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" 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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CHILBLAIN LUPUS 2, INCLUDED (1 family)
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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> rs138603088 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138603088;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/rs138603088?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=rs138603088" 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=rs138603088" 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=RCV000023578 OR RCV000023579 OR RCV000825545 OR RCV001555533 OR RCV005031453" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023578, RCV000023579, RCV000825545, RCV001555533, RCV005031453" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023578...</a>
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<p><strong><em>Aicardi-Goutieres Syndrome 5</em></strong></p><p>
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For discussion of the ile201-to-asn (I201N) mutation in the SAMHD1 gene that was found in compound heterozygous state in affected individuals from a family with Aicardi-Goutieres syndrome-5 (AGS5; <a href="/entry/612952">612952</a>) by <a href="#16" class="mim-tip-reference" title="Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others. <strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong> Nature Genet. 41: 829-832, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19525956">Rice et al. (2009)</a>, see <a href="#0010">606754.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Chilblain Lupus 2</em></strong></p><p>
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In a mother and son with familial chilblain lupus-2 (CHBL2; <a href="/entry/614415">614415</a>), <a href="#14" class="mim-tip-reference" title="Ravenscroft, J. C., Suri, M., Rice, G. I., Szynkiewicz, M., Crow, Y. J. <strong>Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (Letter)</strong> Am. J. Med. Genet. 155A: 235-237, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204240</a>] [<a href="https://doi.org/10.1002/ajmg.a.33778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21204240">Ravenscroft et al. (2011)</a> identified a heterozygous 602T-A transversion in exon 5 of the SAMHD1 gene, resulting in an I201N substitution at a highly conserved residue. The mutation was not found in 450 control alleles. In early childhood, both patients developed recurrent lesions affecting the hands and feet, as well as variable other regions, particularly over the winter months. Both also had sun sensitivity and later developed angiomatous lesions on the fingers, which became persistent. Biopsy of chilblain skin in the mother showed a florid lymphocytic vasculitis, with papillary dermal edema, interface dermatitis, and keratinocyte necrosis, consistent with lupus. The findings pointed to a defect in innate immunity and inflammation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21204240" 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="Crow, Y. J., Chase, D. S., Lowenstein Schmidt, J., Szynkiewicz, M., Forte, G. M. A., Gornall, H. L., Oojageer, A., Anderson, B., Pizzino, A., Helman, G., Abdel-Hamid, M. S., Abdel-Salam, G. M., and 124 others. <strong>Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.</strong> Am. J. Med. Genet. 167A: 296-312, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25604658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25604658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25604658[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/10.1002/ajmg.a.36887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25604658">Crow et al. (2015)</a> stated that they had identified the I201N mutation in 1 family with chilblain lupus but provided no additional information. It was unclear whether this was the same family reported by <a href="#14" class="mim-tip-reference" title="Ravenscroft, J. C., Suri, M., Rice, G. I., Szynkiewicz, M., Crow, Y. J. <strong>Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (Letter)</strong> Am. J. Med. Genet. 155A: 235-237, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204240</a>] [<a href="https://doi.org/10.1002/ajmg.a.33778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21204240">Ravenscroft et al. (2011)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25604658+21204240" 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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Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulos, D., Berka, U., Lienenklaus, S., Peschke, K., Gibbert, K., Wittmann, S., Lindemann, D., Weiss, S., Dahl, A., Naumann, R., Dittmer, U., Kim, B., Mueller, W., Gramberg, T., Roers, A.
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<strong>Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.</strong>
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Cell Rep. 4: 689-696, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23972988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23972988</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23972988[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=23972988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.celrep.2013.07.037" target="_blank">Full Text</a>]
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Coquel, F., Silva, M.-J., Techer, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., Promonet, A., Cribier, A., and 9 others.
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<strong>SAMHD1 acts at stalled replication forks to prevent interferon induction.</strong>
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Nature 557: 57-61, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29670289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29670289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29670289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Crow, Y. J., Chase, D. S., Lowenstein Schmidt, J., Szynkiewicz, M., Forte, G. M. A., Gornall, H. L., Oojageer, A., Anderson, B., Pizzino, A., Helman, G., Abdel-Hamid, M. S., Abdel-Salam, G. M., and 124 others.
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<strong>Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.</strong>
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Am. J. Med. Genet. 167A: 296-312, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25604658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25604658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25604658[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=25604658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.36887" target="_blank">Full Text</a>]
|
|
|
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|
</p>
|
|
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|
|
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|
|
|
|
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|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Dale2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dale, R. C., Gornall, H., Singh-Grewal, D., Alcausin, M., Rice, G. I., Crow, Y. J.
|
|
<strong>Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.</strong>
|
|
Am. J. Med. Genet. 152A: 938-942, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20358604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20358604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20358604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.33359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Goldstone2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G. I., Christodoulou, E., Walker, P. A., Kelly, G., Haire, L. F., Yap, M. W., de Carvalho, L. P. S., Stoye, J. P., Crow, Y. J., Taylor, I. A., Webb, M.
|
|
<strong>HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.</strong>
|
|
Nature 480: 379-382, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22056990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22056990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22056990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature10623" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Gross2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 5/8/2012.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Hrecka2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., Skowronski, J.
|
|
<strong>Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.</strong>
|
|
Nature 474: 658-661, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21720370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21720370</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21720370[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=21720370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature10195" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Laguette2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Munch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., Delsuc, F., Telenti, A., Benkirane, M.
|
|
<strong>Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.</strong>
|
|
Cell Host Microbe 11: 205-217, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22305291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22305291</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22305291[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=22305291" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.chom.2012.01.007" target="_blank">Full Text</a>]
|
|
|
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|
|
</p>
|
|
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|
|
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|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Laguette2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Segeral, E., Yatim, A., Emiliani, S., Schwartz, O., Benkirane, M.
|
|
<strong>SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.</strong>
|
|
Nature 474: 654-657, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21613998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21613998</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21613998[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=21613998" 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/nature10117" target="_blank">Full Text</a>]
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</p>
|
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|
|
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|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
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<a id="Lahouassa2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., Margottin-Goguet, F.
|
|
<strong>SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.</strong>
|
|
Nature Immun. 13: 223-229, 2012. Note: Erratum: Nature Immun. 14: 877 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22327569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22327569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22327569[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=22327569" 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/ni.2236" target="_blank">Full Text</a>]
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|
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</p>
|
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|
|
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|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
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<a id="Leshinsky-Silver2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leshinsky-Silver, E., Malinger, G., Ben-Sira, L., Kidron, D., Cohen, S., Inbar, S., Bezaleli, T., Levine, A., Vinkler, C., Lev, D., Lerman-Sagie, T.
|
|
<strong>A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres syndrome associated with mtDNA deletions.</strong>
|
|
Europ. J. Hum. Genet. 19: 287-292, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21102625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21102625</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21102625[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=21102625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ejhg.2010.213" target="_blank">Full Text</a>]
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</p>
|
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|
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<li>
|
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<a id="12" class="mim-anchor"></a>
|
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<a id="Li2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, N., Zhang, W., Cao, X.
|
|
<strong>Identification of human homologue of mouse IFN-gamma induced protein from human dendritic cells.</strong>
|
|
Immun. Lett. 74: 221-224, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11064105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11064105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11064105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0165-2478(00)00276-5" target="_blank">Full Text</a>]
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|
|
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|
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<a id="13" class="mim-anchor"></a>
|
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<a id="Lim2012" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
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Lim, E. S., Fregoso, O. I., McCoy, C. O., Matsen, F. A., Malik, H. S., Emerman, M.
|
|
<strong>The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.</strong>
|
|
Cell Host Microbe 11: 194-204, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22284954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22284954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22284954[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=22284954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.chom.2012.01.004" target="_blank">Full Text</a>]
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<li>
|
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<a id="14" class="mim-anchor"></a>
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<a id="Ravenscroft2011" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Ravenscroft, J. C., Suri, M., Rice, G. I., Szynkiewicz, M., Crow, Y. J.
|
|
<strong>Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (Letter)</strong>
|
|
Am. J. Med. Genet. 155A: 235-237, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21204240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21204240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21204240" 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.33778" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Rehwinkel2013" class="mim-anchor"></a>
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<div class="">
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Rehwinkel, J., Maelfait, J., Bridgeman, A., Rigby, R., Hayward, B., Liberatore, R. A., Bieniasz, P. D., Towers, G. J., Moita, L. F., Crow, Y. J., Bonthron, D. T., Reis e Sousa, C.
|
|
<strong>SAMHD1-dependent retroviral control and escape in mice.</strong>
|
|
EMBO J. 32: 2454-2462, 2013.
|
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23872947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23872947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23872947[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=23872947" 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/emboj.2013.163" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Rice2009" class="mim-anchor"></a>
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<div class="">
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Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others.
|
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<strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong>
|
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Nature Genet. 41: 829-832, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19525956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19525956</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19525956[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=19525956" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.373" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 09/06/2018
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Paul J. Converse - updated : 01/13/2017<br>3 : 7/27/2015<br>Carol A. Bocchini - updated : 7/27/2015<br>Matthew B. Gross - updated : 5/8/2012<br>Paul J. Converse - updated : 4/2/2012<br>Ada Hamosh - updated : 2/27/2012<br>Cassandra L. Kniffin - updated : 1/5/2012<br>Ada Hamosh - updated : 8/24/2011<br>Cassandra L. Kniffin - updated : 7/11/2011<br>Cassandra L. Kniffin - updated : 11/10/2010<br>Cassandra L. Kniffin - updated : 8/6/2009
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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<span class="mim-text-font">
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Paul J. Converse : 3/7/2002
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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alopez : 09/06/2018
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joanna : 09/27/2017<br>mgross : 01/13/2017<br>mgross : 12/19/2016<br>carol : 10/18/2016<br>carol : 01/04/2016<br>mcolton : 7/27/2015<br>carol : 7/27/2015<br>carol : 7/24/2015<br>mcolton : 7/23/2015<br>mcolton : 4/1/2014<br>carol : 8/16/2013<br>mgross : 5/8/2012<br>terry : 4/2/2012<br>alopez : 3/2/2012<br>terry : 2/27/2012<br>carol : 1/11/2012<br>ckniffin : 1/5/2012<br>alopez : 8/26/2011<br>terry : 8/24/2011<br>wwang : 7/21/2011<br>ckniffin : 7/11/2011<br>wwang : 11/15/2010<br>ckniffin : 11/10/2010<br>wwang : 8/17/2009<br>ckniffin : 8/6/2009<br>mgross : 3/7/2002
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<span class="mim-font">
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<strong>*</strong> 606754
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</h3>
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<h3>
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<span class="mim-font">
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SAM DOMAIN- AND HD DOMAIN-CONTAINING PROTEIN 1; SAMHD1
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</h3>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<h4>
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<span class="mim-font">
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DENDRITIC CELL-DERIVED IFNG-INDUCED PROTEIN; DCIP
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SAMHD1</em></strong>
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<strong>
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<em>
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Cytogenetic location: 20q11.23
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Genomic coordinates <span class="small">(GRCh38)</span> : 20:36,889,773-36,951,708 </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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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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20q11.23
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<span class="mim-font">
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?Chilblain lupus 2
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<span class="mim-font">
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614415
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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Aicardi-Goutieres syndrome 5
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<span class="mim-font">
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612952
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<span class="mim-font">
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>SAMHD1 is a 3-prime exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. It functions as a human immunodeficiency virus (HIV)-1 (see 609423) restriction factor by hydrolyzing dNTPs and decreasing their concentration to a level below that necessary for retroviral reverse transcription (Behrendt et al., 2013). </p>
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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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<p>Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) able to induce a primary T-cell response in vivo. With maturation, DCs shift from antigen-uptake and -processing functions to an antigen-presentation phenotype. By screening an EST database derived from a DC cDNA library for sequences homologous to the mouse gamma-interferon (IFNG; 147570)-induced gene Mg11, followed by RACE, Li et al. (2000) obtained a cDNA encoding SAMHD1, which they termed DCIP. The deduced 626-amino acid protein, which is 72% identical to mouse Mg11, contains several phosphorylation and N-myristoylation sites, an N-glycosylation site, and an amidation site. It has no signal peptide or transmembrane region, suggesting that DCIP is an intracellular protein. RT-PCR analysis detected wide but variable expression in most cell lines tested. Northern blot analysis revealed expression of a 5.2-kb transcript in all tissues tested except brain and thymus. </p><p>Lahouassa et al. (2012) noted that SAMHD1 consists of an N-terminal sterile alpha motif domain and a central HD domain with putative nucleotidase and phosphodiesterase activities, respectively. They stated that dendritic cells, monocyte-derived macrophages, and HIV-1-permissive CD4 (186940)-positive T cells have high, moderate, and low SAMHD1 expression, respectively. </p>
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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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</div>
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<span class="mim-text-font">
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<p>Gross (2012) mapped the SAMHD1 gene to chromosome 20q11.23 based on an alignment of the SAMHD1 sequence (GenBank AB013847) with the genomic sequence (GRCh37).</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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<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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<span class="mim-text-font">
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<p>In Myd88 (602170)-null mice that have impaired immune response, Rice et al. (2009) showed that transfection of macrophages with immunostimulatory DNA resulted in upregulation of Samhd1 expression. Macrophages from Myd88/Ifnar1 (107450) double-knockout mice showed that this expression was interferon-dependent. The findings were consistent with the hypothesis that SAMHD1 expression can be induced by type 1 interferons and suggested that SAMHD1 may also act as a negative regulator of the immunostimulatory DNA response. </p><p>Laguette et al. (2011) identified SAMHD1 as the restriction factor that renders human dendritic and myeloid cells largely refractory to HIV-1 infection. SAMHD1 is a protein involved in Aicardi-Goutieres syndrome (see 612952), a genetic encephalopathy with symptoms mimicking congenital viral infection, that has been proposed to act as a negative regulator of the interferon response. Laguette et al. (2011) showed that Vpx, the primate lentivirus auxiliary protein, induces proteasomal degradation of SAMHD1. Silencing of SAMHD1 in nonpermissive cell lines alleviated HIV-1 restriction and was associated with a significant accumulation of viral DNA in infected cells. Concurrently, overexpression of SAMHD1 in sensitive cells inhibited HIV-1 infection. The putative phosphohydrolase activity of SAMHD1 is probably required for HIV-1 restriction. Vpx-mediated relief of restriction was abolished in SAMHD1-negative cells. Finally, silencing of SAMHD1 markedly increased the susceptibility of monocytic-derived dendritic cells to infection. Laguette et al. (2011) concluded that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle. </p><p>Hrecka et al. (2011) independently demonstrated that the inhibition of HIV-1 infection in macrophages involves the cellular SAMHD1 protein. Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase (see 617259), leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutieres syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Hrecka et al. (2011) concluded that their findings showed that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncovered an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens. </p><p>Goldstone et al. (2011) showed that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. Based on these findings and analysis of the crystal structure of the catalytic core of SAMHD1, Goldstone et al. (2011) proposed that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolyzing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral cDNA synthesis. </p><p>By measuring intracellular dNTP pools in human myeloid cells, Lahouassa et al. (2012) found that SAMHD1 lowered the dNTP concentration to an amount that failed to support reverse transcription, thereby establishing a cellular state that was not permissive to lentiviral infection. Vpx induced degradation of SAMHD1, resulting in a large intracellular dNTP pool and restoration of permissiveness to infection. Lahouassa et al. (2012) proposed that nucleotide pool depletion may be a general mechanism for protecting cells from infectious agents that replicate through a DNA intermediate. </p><p>Coquel et al. (2018) demonstrated that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11 (600814). This function activates the ATR (601215)-CHK1 (603078) checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS (613973)-STING (612374) pathway to induce expression of proinflammatory type I interferons (e.g., IFNA1, 147660). Coquel et al. (2018) concluded that SAMHD1 is an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Goldstone et al. (2011) solved the crystal structure of the catalytic core of SAMHD1, which revealed that the protein is dimeric and indicated a molecular basis for dGTP stimulation of catalytic activity against dNTPs. </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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<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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<span class="mim-text-font">
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<p><strong><em>Aicardi-Goutieres Syndrome 5</em></strong></p><p>
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By genomewide linkage analysis and candidate gene sequencing of multiple families with Aicardi-Goutieres syndrome (AGS5; 612952), Rice et al. (2009) identified homozygous or compound heterozygous mutations in the SAMHD1 gene (see, e.g., 606754.0001-606754.0007). Several of the families were consanguineous. All of the mutations involved highly conserved residues, segregated with the disease, and all unaffected parents tested were heterozygous for the mutations. </p><p><strong><em>Chilblain Lupus 2</em></strong></p><p>
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In a mother and son with chilblain lupus (CHBL2; 614415), Ravenscroft et al. (2011) identified a heterozygous mutation in the SAMHD1 gene (I201N; 606754.0011). The findings suggested that SAMHD1 is involved in innate immunity and inflammation. </p>
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<h4>
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<span class="mim-font">
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<strong>Evolution</strong>
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</span>
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<span class="mim-text-font">
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<p>Laguette et al. (2012) reiterated that while pandemic HIV-1 has no means to counteract SAMHD1 restriction, nonpandemic HIV-2 and certain simian immunodeficiency virus (SIV) strains encode the auxiliary protein Vpx that potently overcomes the block to viral replication constituted by SAMHD1 by promoting its degradation by the proteasome machinery. Evolutionary analysis by Laguette et al. (2012) showed that SAMHD1 experienced strong positive selection episodes during primate evolution. Identification of SAMHD1 residues under positive selection allowed mapping of the Vpx interaction domain of SAMHD1 to the C-terminal region. SAMHD1 proteins of apes, monkeys, and lemurs were all active against HIV-1, whereas Vpx degraded and antagonized SAMHD1 in a species-specific manner. Laguette et al. (2012) questioned whether the presence of Vpx represents an advantage favoring cross-species transmission and observed that Vpx appears to be dispensable for persistence and spread in humans. </p><p>Lim et al. (2012) noted that only 2 of 8 primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. By functional analysis, they found that multiple Vpx proteins shared the ability to degrade SAMHD1, but that this ability was often host specific. Additionally, some Vpr proteins from viruses lacking Vpx could also potently degrade SAMHD1. Evolutionary analysis showed that the ability to degrade SAMHD1 resulted from neofunctionalization of Vpr that preceded the acquisition of Vpx in primate lentiviruses. Lim et al. (2012) concluded that Vpr gained a new function to degrade SAMHD1 once during viral evolution, thereby initiating an evolutionary 'arms race' with SAMHD1. However, they noted that many lentiviral lineages, including the precursors of HIV-1, never acquired this function. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>By generating mice lacking Samhd1, Behrendt et al. (2013) showed that mouse Samhd1 reduced cellular dNTP concentrations and restricted retroviral reverse transcription in lymphocytes, macrophages, and dendritic cells. Absence of Samhd1 triggered Ifnb (IFNB1; 147640)-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types. Behrendt et al. (2013) proposed that Samhd1-deficient mice model important features associated with pathogenic type I IFN responses involved in AGS and SLE pathogenesis. </p><p>Independently, Rehwinkel et al. (2013) generated Samhd1 -/- mice and found that they did not develop autoimmune disease, despite displaying a type I IFN signature in spleen, macrophages, and fibroblasts. Cells lacking Samhd1 had elevated dNTP levels, but the deficiency did not lead to increased infection with pseudotyped HIV-1 vectors, likely due to high concentrations of dNTPs in Samhd1 -/- cells. A mutant HIV-1 vector having a reverse transcriptase with reduced affinity for dNTPs was sensitive to Samhd1-dependent restriction in cultured cells and mice. Rehwinkel et al. (2013) concluded that SAMHD1 can restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily conserved antiviral mechanism. They suggested that HIV-1 may have evolved with a polymerase active at low dNTP concentrations to circumvent SAMHD1 restriction. </p>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>11 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 AICARDI-GOUTIERES SYNDROME 5</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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SAMHD1, GLY209SER
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<br />
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SNP: rs121434516,
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gnomAD: rs121434516,
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ClinVar: RCV000004281
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a Hungarian family with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a homozygous 625G-A transition in exon 5 of the SAMHD1 gene, resulting in a gly209-to-ser (G209S) substitution at a highly conserved residue. The parents were third cousins. One of the patients died at age 5 years. </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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<strong>.0002 AICARDI-GOUTIERES SYNDROME 5</strong>
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</span>
|
|
</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SAMHD1, ARG145TER
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<br />
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SNP: rs121434517,
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|
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|
gnomAD: rs121434517,
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|
|
|
ClinVar: RCV000004282, RCV001826413, RCV002476923, RCV004700185
|
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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 unrelated families of Maltese origin with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a homozygous 433C-T transition in exon 4 of the SAMHD1 gene, resulting in arg145-to-ter (R145X) substitution at a highly conserved residue. </p><p>In 2 sibs with variable manifestations of AGS5, Dale et al. (2010) identified compound heterozygosity for 2 mutations in the SAMHD1 gene: the R145X mutation and a 490C-T transition in exon 4, resulting in an arg164-to-ter (R164X; 606754.0008) substitution. The father was of Maltese origin, and both the father and paternal grandfather reportedly had mild skin involvement, but genetic studies were not performed. </p>
|
|
</span>
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</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 AICARDI-GOUTIERES SYNDROME 5</strong>
|
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</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SAMHD1, IVS14AS, G-C, -1
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<br />
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SNP: rs515726143,
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gnomAD: rs515726143,
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ClinVar: RCV000114350
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Pakistani patient with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a homozygous G-to-C transversion in intron 14 of the SAMHD1 gene (1609-1G-C), resulting in a splice site mutation and the skipping of exon 15 as well as other abnormal transcripts. The parents were related as first cousins. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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SAMHD1, GLN149TER
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<br />
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|
SNP: rs121434518,
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ClinVar: RCV000004285
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Indian family with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a homozygous 445C-T transition in exon 4 of the SAMHD1 gene, resulting in a gln149-to-ter (Q149X) substitution. Patient cells carrying the Q149X substitution showed localization of the mutant SAMHD1 protein to the nucleus, confirming that the derived mRNA is not subject to nonsense-mediated decay, and indicating that the first 149 amino acids of the protein are sufficient for nuclear localization. However, expression was diminished compared to wildtype and proper localization to internal nuclear structures was less clear. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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SAMHD1, GLN548TER
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|
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<br />
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|
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SNP: rs121434519,
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|
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|
|
|
gnomAD: rs121434519,
|
|
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|
|
|
ClinVar: RCV000004286, RCV005031386
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a homozygous 1642C-T transition in exon 15 of the SAMHD1 gene, resulting in a gln548-to-ter (Q548X) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
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|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, HIS123PRO
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|
|
|
<br />
|
|
|
|
SNP: rs121434520,
|
|
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|
|
|
gnomAD: rs121434520,
|
|
|
|
|
|
ClinVar: RCV000004287
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 French sibs with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified a compound heterozygosity for a 368A-C transversion in exon 4 of the SAMHD1 gene, resulting in a his123-to-pro (H123P) substitution, and a 760A-G transition in exon 7, resulting in a met254-to-val (M254V; 606754.0007) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, MET254VAL
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121434521,
|
|
|
|
|
|
|
|
ClinVar: RCV000004288
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the met254-to-val (M254V) mutation in the SAMHD1 gene that was found in compound heterozygous state in 2 sibs with Aicardi-Goutieres syndrome-5 (AGS5; 612952) by Rice et al. (2009), see 606754.0006. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, ARG164TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607027,
|
|
|
|
|
|
gnomAD: rs267607027,
|
|
|
|
|
|
ClinVar: RCV000004284, RCV001831512, RCV005025003
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg164-to-ter (R164X) mutation in the SAMHD1 gene that was found in compound heterozygous state in 2 sibs with variable manifestations of Aicardi-Goutieres syndrome-5 (AGS5; 612952) by Dale et al. (2010), see 606754.0002. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, 9.1-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000023576
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy, born of unrelated Ashkenazi Jewish parents, with severe Aicardi-Goutieres syndrome-5 (AGS5; 612952) including mitochondrial DNA deletions, Leshinsky-Silver et al. (2011) identified a homozygous 9.1-kb deletion involving the SAMHD1 gene. The deletion started upstream of the promoter, encompassed exon 1, and ended in intron 1. The deletion also included the 3-prime end of RBL1 (116957), which may have contributed to the severe phenotype. The parents were each heterozygous for the 9.1-kb deletion, which was not identified in 100 Ashkenazi Jewish controls. The patient presented at age 3 weeks with failure to thrive, poor growth, and lack of development. He had central hypotonia with brisk tendon reflexes and choreoathetoid movements. Brain MRI showed extensive white matter destruction, delayed myelination, hypoplasia of the corpus callosum, severe cortical atrophy, destructive lesions of the aqueductal body and pons, and pathologic lesions in the frontal lobe and basal ganglia. Blood samples showed increased serum lactate, anemia, and thrombocytosis. He had profound mental retardation, poor growth, and severe irritability, and died at age 15 months. Two subsequent pregnancies were terminated after studies showed periventricular white matter lesions and hyperechogenic foci in the basal ganglia between 28 and 34 weeks' gestation. Southern blot analysis of patient skeletal muscle and liver tissue showed multiple mitochondrial DNA deletions, which were not found in blood and fibroblasts, and there were similar findings in fetal autopsy tissues. Leshinsky-Silver et al. (2011) suggested that mutant SAMHD1 causes an induction of the cell intrinsic antiviral response, apoptosis, and mitochondrial DNA destruction. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, ARG143CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906948,
|
|
|
|
|
|
gnomAD: rs387906948,
|
|
|
|
|
|
ClinVar: RCV000023577
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Canadian family with Aicardi-Goutieres syndrome-5 (AGS5; 612952), Rice et al. (2009) identified compound heterozygosity for 2 mutations in the SAMHD1 gene: a 427C-T transition in exon 4, resulting in an arg143-to-cys (R143C) substitution, and a 602T-A transversion in exon 5, resulting in an ile201-to-asn (I201N; 606754.0011) substitution. Both mutations occurred at highly conserved residues. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 AICARDI-GOUTIERES SYNDROME 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CHILBLAIN LUPUS 2, INCLUDED (1 family)
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SAMHD1, ILE201ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs138603088,
|
|
|
|
|
|
gnomAD: rs138603088,
|
|
|
|
|
|
ClinVar: RCV000023578, RCV000023579, RCV000825545, RCV001555533, RCV005031453
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Aicardi-Goutieres Syndrome 5</em></strong></p><p>
|
|
For discussion of the ile201-to-asn (I201N) mutation in the SAMHD1 gene that was found in compound heterozygous state in affected individuals from a family with Aicardi-Goutieres syndrome-5 (AGS5; 612952) by Rice et al. (2009), see 606754.0010. </p><p><strong><em>Chilblain Lupus 2</em></strong></p><p>
|
|
In a mother and son with familial chilblain lupus-2 (CHBL2; 614415), Ravenscroft et al. (2011) identified a heterozygous 602T-A transversion in exon 5 of the SAMHD1 gene, resulting in an I201N substitution at a highly conserved residue. The mutation was not found in 450 control alleles. In early childhood, both patients developed recurrent lesions affecting the hands and feet, as well as variable other regions, particularly over the winter months. Both also had sun sensitivity and later developed angiomatous lesions on the fingers, which became persistent. Biopsy of chilblain skin in the mother showed a florid lymphocytic vasculitis, with papillary dermal edema, interface dermatitis, and keratinocyte necrosis, consistent with lupus. The findings pointed to a defect in innate immunity and inflammation. </p><p>Crow et al. (2015) stated that they had identified the I201N mutation in 1 family with chilblain lupus but provided no additional information. It was unclear whether this was the same family reported by Ravenscroft et al. (2011). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
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|
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Behrendt, R., Schumann, T., Gerbaulet, A., Nguyen, L. A., Schubert, N., Alexopoulos, D., Berka, U., Lienenklaus, S., Peschke, K., Gibbert, K., Wittmann, S., Lindemann, D., Weiss, S., Dahl, A., Naumann, R., Dittmer, U., Kim, B., Mueller, W., Gramberg, T., Roers, A.
|
|
<strong>Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.</strong>
|
|
Cell Rep. 4: 689-696, 2013.
|
|
|
|
|
|
[PubMed: 23972988]
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|
|
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|
|
[Full Text: https://doi.org/10.1016/j.celrep.2013.07.037]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Coquel, F., Silva, M.-J., Techer, H., Zadorozhny, K., Sharma, S., Nieminuszczy, J., Mettling, C., Dardillac, E., Barthe, A., Schmitz, A.-L., Promonet, A., Cribier, A., and 9 others.
|
|
<strong>SAMHD1 acts at stalled replication forks to prevent interferon induction.</strong>
|
|
Nature 557: 57-61, 2018.
|
|
|
|
|
|
[PubMed: 29670289]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-018-0050-1]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crow, Y. J., Chase, D. S., Lowenstein Schmidt, J., Szynkiewicz, M., Forte, G. M. A., Gornall, H. L., Oojageer, A., Anderson, B., Pizzino, A., Helman, G., Abdel-Hamid, M. S., Abdel-Salam, G. M., and 124 others.
|
|
<strong>Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.</strong>
|
|
Am. J. Med. Genet. 167A: 296-312, 2015.
|
|
|
|
|
|
[PubMed: 25604658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.36887]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dale, R. C., Gornall, H., Singh-Grewal, D., Alcausin, M., Rice, G. I., Crow, Y. J.
|
|
<strong>Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.</strong>
|
|
Am. J. Med. Genet. 152A: 938-942, 2010.
|
|
|
|
|
|
[PubMed: 20358604]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33359]
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldstone, D. C., Ennis-Adeniran, V., Hedden, J. J., Groom, H. C. T., Rice, G. I., Christodoulou, E., Walker, P. A., Kelly, G., Haire, L. F., Yap, M. W., de Carvalho, L. P. S., Stoye, J. P., Crow, Y. J., Taylor, I. A., Webb, M.
|
|
<strong>HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase.</strong>
|
|
Nature 480: 379-382, 2011.
|
|
|
|
|
|
[PubMed: 22056990]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10623]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 5/8/2012.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Hrecka, K., Hao, C., Gierszewska, M., Swanson, S. K., Kesik-Brodacka, M., Srivastava, S., Florens, L., Washburn, M. P., Skowronski, J.
|
|
<strong>Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein.</strong>
|
|
Nature 474: 658-661, 2011.
|
|
|
|
|
|
[PubMed: 21720370]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10195]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Laguette, N., Rahm, N., Sobhian, B., Chable-Bessia, C., Munch, J., Snoeck, J., Sauter, D., Switzer, W. M., Heneine, W., Kirchhoff, F., Delsuc, F., Telenti, A., Benkirane, M.
|
|
<strong>Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.</strong>
|
|
Cell Host Microbe 11: 205-217, 2012.
|
|
|
|
|
|
[PubMed: 22305291]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.chom.2012.01.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
|
Laguette, N., Sobhian, B., Casartelli, N., Ringeard, M., Chable-Bessia, C., Segeral, E., Yatim, A., Emiliani, S., Schwartz, O., Benkirane, M.
|
|
<strong>SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx.</strong>
|
|
Nature 474: 654-657, 2011.
|
|
|
|
|
|
[PubMed: 21613998]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10117]
|
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|
|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
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|
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Lahouassa, H., Daddacha, W., Hofmann, H., Ayinde, D., Logue, E. C., Dragin, L., Bloch, N., Maudet, C., Bertrand, M., Gramberg, T., Pancino, G., Priet, S., Canard, B., Laguette, N., Benkirane, M., Transy, C., Landau, N. R., Kim, B., Margottin-Goguet, F.
|
|
<strong>SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.</strong>
|
|
Nature Immun. 13: 223-229, 2012. Note: Erratum: Nature Immun. 14: 877 only, 2013.
|
|
|
|
|
|
[PubMed: 22327569]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ni.2236]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Leshinsky-Silver, E., Malinger, G., Ben-Sira, L., Kidron, D., Cohen, S., Inbar, S., Bezaleli, T., Levine, A., Vinkler, C., Lev, D., Lerman-Sagie, T.
|
|
<strong>A large homozygous deletion in the SAMHD1 gene causes atypical Aicardi-Goutieres syndrome associated with mtDNA deletions.</strong>
|
|
Europ. J. Hum. Genet. 19: 287-292, 2011.
|
|
|
|
|
|
[PubMed: 21102625]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2010.213]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
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Li, N., Zhang, W., Cao, X.
|
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<strong>Identification of human homologue of mouse IFN-gamma induced protein from human dendritic cells.</strong>
|
|
Immun. Lett. 74: 221-224, 2000.
|
|
|
|
|
|
[PubMed: 11064105]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0165-2478(00)00276-5]
|
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</p>
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</li>
|
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Lim, E. S., Fregoso, O. I., McCoy, C. O., Matsen, F. A., Malik, H. S., Emerman, M.
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<strong>The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.</strong>
|
|
Cell Host Microbe 11: 194-204, 2012.
|
|
|
|
|
|
[PubMed: 22284954]
|
|
|
|
|
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[Full Text: https://doi.org/10.1016/j.chom.2012.01.004]
|
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</p>
|
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</li>
|
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<li>
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Ravenscroft, J. C., Suri, M., Rice, G. I., Szynkiewicz, M., Crow, Y. J.
|
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<strong>Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (Letter)</strong>
|
|
Am. J. Med. Genet. 155A: 235-237, 2011.
|
|
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|
|
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[PubMed: 21204240]
|
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|
|
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[Full Text: https://doi.org/10.1002/ajmg.a.33778]
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</p>
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</li>
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Rehwinkel, J., Maelfait, J., Bridgeman, A., Rigby, R., Hayward, B., Liberatore, R. A., Bieniasz, P. D., Towers, G. J., Moita, L. F., Crow, Y. J., Bonthron, D. T., Reis e Sousa, C.
|
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<strong>SAMHD1-dependent retroviral control and escape in mice.</strong>
|
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EMBO J. 32: 2454-2462, 2013.
|
|
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[PubMed: 23872947]
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[Full Text: https://doi.org/10.1038/emboj.2013.163]
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Rice, G. I., Bond, J., Asipu, A., Brunette, R. L., Manfield, I. W., Carr, I. M., Fuller, J. C., Jackson, R. M., Lamb, T., Briggs, T. A., Ali, M., Gornall, H., and 39 others.
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<strong>Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response.</strong>
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Nature Genet. 41: 829-832, 2009.
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[PubMed: 19525956]
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[Full Text: https://doi.org/10.1038/ng.373]
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Ada Hamosh - updated : 09/06/2018<br>Paul J. Converse - updated : 01/13/2017<br>3 : 7/27/2015<br>Carol A. Bocchini - updated : 7/27/2015<br>Matthew B. Gross - updated : 5/8/2012<br>Paul J. Converse - updated : 4/2/2012<br>Ada Hamosh - updated : 2/27/2012<br>Cassandra L. Kniffin - updated : 1/5/2012<br>Ada Hamosh - updated : 8/24/2011<br>Cassandra L. Kniffin - updated : 7/11/2011<br>Cassandra L. Kniffin - updated : 11/10/2010<br>Cassandra L. Kniffin - updated : 8/6/2009
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