3904 lines
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Entry
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- *608512 - NEUTROPHIL CYTOSOLIC FACTOR 1; NCF1
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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">*608512</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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<a href="#description">Description</a>
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608512">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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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=ENSG00000158517;t=ENST00000289473" 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=653361" 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=608512" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000158517;t=ENST00000289473" 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_000265" 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_000265" 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=608512" 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://www.proteinatlas.org/search/NCF1" 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/189949,553612,808095,2754713,6983940,12803939,13345794,13345796,41389091,41472587,62897995,158257620,193785443,194389284,221046070,528078313,1384010320" 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/P14598" 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=653361" 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=ENSG00000158517;t=ENST00000289473" 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=NCF1" 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=NCF1" 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+653361" 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/NCF1" 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:653361" 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/653361" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr7&hgg_gene=ENST00000289473.11&hgg_start=74774011&hgg_end=74789315&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 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/gene-dosage/HGNC:7660" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/ncf1" 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=608512[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=608512[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000158517" 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=NCF1" 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=NCF1" 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=NCF1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://structure.bmc.lu.se/idbase/NCF1base/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=NCF1&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/PA31463" 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:7660" 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://www.mousephenotype.org/data/genes/MGI:97283" 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/NCF1#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:97283" 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/653361/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=653361" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-031006-6" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:653361" 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=NCF1&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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608512
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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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NEUTROPHIL CYTOSOLIC FACTOR 1; NCF1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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NOXO2<br />
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p47-PHOX
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=NCF1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NCF1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/7/340?start=-3&limit=10&highlight=340">7q11.23</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:74774011-74789315&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'})">7:74,774,011-74,789,315</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/7/340?start=-3&limit=10&highlight=340">
|
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7q11.23
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Chronic granulomatous disease 1, autosomal recessive
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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|
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<a href="/entry/233700"> 233700 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/608512" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608512" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
|
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</h4>
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</div>
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<p>Neutrophil cytosolic factor-1 (NCF1), also known as p47-phox (for phagocyte oxidase), is a component of the NADPH oxidase complex (<a href="#21" class="mim-tip-reference" title="Volpp, B. D., Nauseef, W. M., Donelson, J. E., Moser, D. R., Clark, R. A. <strong>Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase.</strong> Proc. Nat. Acad. Sci. 86: 7195-7199, 1989. Note: Erratum: Proc. Nat. Acad. Sci. 86: 9563 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2550933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2550933</a>] [<a href="https://doi.org/10.1073/pnas.86.18.7195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2550933">Volpp et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2550933" 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 screening a promyelocytic leukemia cDNA library, <a href="#21" class="mim-tip-reference" title="Volpp, B. D., Nauseef, W. M., Donelson, J. E., Moser, D. R., Clark, R. A. <strong>Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase.</strong> Proc. Nat. Acad. Sci. 86: 7195-7199, 1989. Note: Erratum: Proc. Nat. Acad. Sci. 86: 9563 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2550933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2550933</a>] [<a href="https://doi.org/10.1073/pnas.86.18.7195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2550933">Volpp et al. (1989)</a> cloned and sequenced a cDNA encoding the 47-kD component of the NADPH oxidase system. The 390-amino acid protein has an N-terminal glycine residue, which may serve to translocate the protein to the plasma membrane, several phosphorylation sites, a potential nucleotide-binding site, and a region of homology to some protein kinases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2550933" 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="#16" class="mim-tip-reference" title="Rodaway, A. R. F., Teahan, C. G., Casimir, C. M., Segal, A. W., Bentley, D. L. <strong>Characterization of the 47-kilodalton autosomal chronic granulomatous disease protein: tissue-specific expression and transcriptional control by retinoic acid.</strong> Molec. Cell. Biol. 10: 5388-5396, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2398896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2398896</a>] [<a href="https://doi.org/10.1128/mcb.10.10.5388-5396.1990" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2398896">Rodaway et al. (1990)</a> isolated and characterized a full-length cDNA clone for neutrophil cytosolic factor-1. An antiserum raised against the predicted C terminus of the protein detected a 47-kD polypeptide that is present in normal neutrophils, but not in those from patients with autosomal chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>). The protein is associated with the vacuolar membrane and is phosphorylated in response to phorbol ester treatment. Gene expression was limited to 3 cell types: granulocytes, monocytes, and B lymphocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2398896" 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>To study the cis elements and trans-acting factors responsible for p47-phox expression, <a href="#13" class="mim-tip-reference" title="Li, S.-L., Valente, A. J., Zhao, S.-J., Clark, R. A. <strong>PU.1 is essential for p47(phox) promoter activity in myeloid cells.</strong> J. Biol. Chem. 272: 17802-17809, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9211934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9211934</a>] [<a href="https://doi.org/10.1074/jbc.272.28.17802" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9211934">Li et al. (1997)</a> cloned and characterized the p47-phox promoter. A predominant transcriptional start site was identified 21 nucleotides upstream of the translation initiation codon. Transient transfections of HL60 human myeloid cells were performed with a series of 5-prime-deletion p47-phox-luciferase reporter constructs to identify the gene promoter sequences. The -224 and -86 constructs had the strongest p47-phox promoter activity, whereas the -46 construct showed a major reduction in activity and the -36 construct a complete loss of activity. DNase I footprint analysis identified a protected region from -37 to -53. This region containing a consensus PU.1 (<a href="/entry/165170">165170</a>) site bound specifically both PU.1 present in nuclear extracts and PU.1 synthesized in vitro. Mutations of this site eliminated PU.1 binding and abolished the ability of the p47-phox promoter to direct expression of the reporter gene. <a href="#13" class="mim-tip-reference" title="Li, S.-L., Valente, A. J., Zhao, S.-J., Clark, R. A. <strong>PU.1 is essential for p47(phox) promoter activity in myeloid cells.</strong> J. Biol. Chem. 272: 17802-17809, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9211934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9211934</a>] [<a href="https://doi.org/10.1074/jbc.272.28.17802" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9211934">Li et al. (1997)</a> concluded that p47-phox promoter activity requires PU.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9211934" 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="#21" class="mim-tip-reference" title="Volpp, B. D., Nauseef, W. M., Donelson, J. E., Moser, D. R., Clark, R. A. <strong>Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase.</strong> Proc. Nat. Acad. Sci. 86: 7195-7199, 1989. Note: Erratum: Proc. Nat. Acad. Sci. 86: 9563 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2550933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2550933</a>] [<a href="https://doi.org/10.1073/pnas.86.18.7195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2550933">Volpp et al. (1989)</a> found that, in a cell-free NADPH oxidase system, fusion p47-phox proteins augmented superoxide generation and reconstituted the cytosolic defect of a patient with autosomal chronic granulomatous disease type I (<a href="/entry/233700">233700</a>) who was missing the p47-phox protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2550933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunoprecipitation analysis, <a href="#12" class="mim-tip-reference" title="Kanai, F., Liu, H., Field, S. J., Akbary, H., Matsuo, T., Brown, G. E., Cantley, L. C., Yaffe, M. B. <strong>The PX domains of p47phox and p40phox bind to lipid products of PI(3)K.</strong> Nature Cell Biol. 3: 675-678, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11433300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11433300</a>] [<a href="https://doi.org/10.1038/35083070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11433300">Kanai et al. (2001)</a> showed that mutation of arg57 in the PX domain of p40-phox (NCF4; <a href="/entry/601488">601488</a>) or of the analogous residue, arg42, in p47-phox eliminated phosphoinositide binding. Mutation of arg90 in p47-phox markedly reduced, but did not eliminate, phosphoinositide binding. <a href="#12" class="mim-tip-reference" title="Kanai, F., Liu, H., Field, S. J., Akbary, H., Matsuo, T., Brown, G. E., Cantley, L. C., Yaffe, M. B. <strong>The PX domains of p47phox and p40phox bind to lipid products of PI(3)K.</strong> Nature Cell Biol. 3: 675-678, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11433300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11433300</a>] [<a href="https://doi.org/10.1038/35083070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11433300">Kanai et al. (2001)</a> concluded that PX domains are specific phosphoinositide-binding modules and that different PX domains have different phosphoinositide specificities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11433300" 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="#11" class="mim-tip-reference" title="Jackson, S. H., Devadas, S., Kwon, J., Pinto, L. A., Williams, M. S. <strong>T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation.</strong> Nature Immun. 5: 818-827, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15258578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15258578</a>] [<a href="https://doi.org/10.1038/ni1096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15258578">Jackson et al. (2004)</a> reported that activated mouse T cells deficient in either gp91-phox (CYBB; <a href="/entry/300481">300481</a>) or p47-phox showed enhanced activation of Erk (see MAPK3; <a href="/entry/601795">601795</a>) and Mek (see MAP2K1; <a href="/entry/176872">176872</a>), diminished expression of phagocyte-type NADPH oxidase, and a relative increase in Th1-type cytokine secretion. They suggested that similar alterations may be found in patients with chronic granulomatous disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15258578" 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>During inflammation, indoleamine 2,3-dioxygenase (IDO; <a href="/entry/147435">147435</a>) is upregulated in dendritic cells and phagocytes by proinflammatory stimuli, most notably, interferon-gamma (IFNG; <a href="/entry/147570">147570</a>), and the enzyme then uses superoxide as a 'cofactor' for oxidative cleavage of the indole ring of tryptophan, yielding an intermediate that deformylates to L-kynurenine. <a href="#18" class="mim-tip-reference" title="Romani, L., Fallarino, F., De Luca, A., Montagnoli, C., D'Angelo, C., Zelante, T., Vacca, C., Bistoni, F., Fioretti, M. C., Grohmann, U., Segal, B. H., Puccetti, P. <strong>Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.</strong> Nature 451: 211-215, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18185592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18185592</a>] [<a href="https://doi.org/10.1038/nature06471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18185592">Romani et al. (2008)</a> demonstrated that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in p47-deficient CGD mice with lethal pulmonary aspergillosis (see <a href="/entry/614079">614079</a>), leading to unrestrained V-gamma-1+ gamma-delta T-cell reactivity, dominant production of interleukin-17 (IL17; <a href="/entry/603149">603149</a>), defective regulatory T-cell activity, and acute inflammatory lung injury. Although beneficial effects are induced by IL17 neutralization or gamma-delta T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes coadministration of recombinant IFNG, restores production of downstream immunoactive metabolites and enables the emergence of regulatory V-gamma-4+ gamma-delta and Foxp3+ (<a href="/entry/300292">300292</a>) alpha-beta T cells. Therefore, <a href="#18" class="mim-tip-reference" title="Romani, L., Fallarino, F., De Luca, A., Montagnoli, C., D'Angelo, C., Zelante, T., Vacca, C., Bistoni, F., Fioretti, M. C., Grohmann, U., Segal, B. H., Puccetti, P. <strong>Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.</strong> Nature 451: 211-215, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18185592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18185592</a>] [<a href="https://doi.org/10.1038/nature06471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18185592">Romani et al. (2008)</a> concluded that paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18185592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Hsieh, C. L., Leto, T. L., Lomax, K. J., Malech, H. L., Francke, U. <strong>The genes for two neutrophil cytosol factors that are deficient in autosomal forms of chronic granulomatous disease are on human chromosome 10 (47 kD), and chromosome 1 cen-q32 (65 kD). (Abstract)</strong> Cytogenet. Cell Genet. 51: 1015-1016, 1989."None>Hsieh et al. (1989)</a> concluded from Southern blot analysis of hybrid cell DNAs that the NCF1 gene is located on chromosome 10; however, by Southern analysis of somatic cell hybrid lines and chromosomal in situ hybridization, <a href="#6" class="mim-tip-reference" title="Francke, U., Hsieh, C.-L., Foellmer, B. E., Lomax, K. J., Malech, H. L., Leto, T. L. <strong>Genes for two autosomal recessive forms of chronic granulomatous disease assigned to 1q25 (NCF2) and 7q11.23 (NCF1).</strong> Am. J. Hum. Genet. 47: 483-492, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2393022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2393022</a>]" pmid="2393022">Francke et al. (1990)</a> assigned the NCF1 gene to 7q11.23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2393022" 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>Pseudogenes</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Gorlach, A., Lee, P. L., Roesler, J., Hopkins, P. J., Christensen, B., Green, E. D., Chanock, S. J., Curnutte, J. T. <strong>A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 100: 1907-1918, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329953</a>] [<a href="https://doi.org/10.1172/JCI119721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9329953">Gorlach et al. (1997)</a> identified a highly homologous p47-phox pseudogene which colocalized with the NCF1 gene to 7q11.23. The localization of the pseudogene was determined by analyzing DNA from a panel of human/hamster hybrid cell lines and of a YAC library highly enriched for chromosome 7. This was an unprocessed type of pseudogene, which presumably arose by gene duplication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9329953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Chronic Granulomatous Disease, Autosomal Recessive, 1</em></strong></p><p>
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In 3 unrelated patients with autosomal recessive CGD1, <a href="#1" class="mim-tip-reference" title="Casimir, C. M., Bu-Ghanim, H. N., Rodaway, A. R. F., Bentley, D. L., Rowe, P., Segal, A. W. <strong>Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.</strong> Proc. Nat. Acad. Sci. 88: 2753-2757, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2011585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2011585</a>] [<a href="https://doi.org/10.1073/pnas.88.7.2753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2011585">Casimir et al. (1991)</a> identified a homozygous 2-bp deletion in the NCF1 gene (<a href="#0001">608512.0001</a>). <a href="#1" class="mim-tip-reference" title="Casimir, C. M., Bu-Ghanim, H. N., Rodaway, A. R. F., Bentley, D. L., Rowe, P., Segal, A. W. <strong>Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.</strong> Proc. Nat. Acad. Sci. 88: 2753-2757, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2011585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2011585</a>] [<a href="https://doi.org/10.1073/pnas.88.7.2753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2011585">Casimir et al. (1991)</a> stated that about 30% of CGD cases are autosomal recessive and that more than 90% of the autosomal recessive cases have a defect in the 47-kD cytosolic protein. <a href="#7" class="mim-tip-reference" title="Gorlach, A., Lee, P. L., Roesler, J., Hopkins, P. J., Christensen, B., Green, E. D., Chanock, S. J., Curnutte, J. T. <strong>A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 100: 1907-1918, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329953</a>] [<a href="https://doi.org/10.1172/JCI119721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9329953">Gorlach et al. (1997)</a> reported that the 2-bp mutation is carried in a closely linked pseudogene(s) and suggested that the gene mutation is caused by homologous recombination between the wildtype and pseudogene(s). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9329953+2011585" 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>Unlike other CGD subtypes, in which there is great heterogeneity among mutations, 97% of affected alleles in patients with p47-phox deficiency carry the 2-bp deletion in the NCF1 gene (<a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al., 2001</a>). This unusually high incidence results from recombination events between NCF1 and its highly homologous pseudogenes which carry the deletion. Of 50 consecutive patients with CGD due to deficiency of NCF1, <a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al. (2001)</a> identified 4 who were heterozygous for the GT deletion as well as 2 whose DNA appeared normal at this position. In each of the 4 patients who were heterozygous for the GT deletion, an additional novel mutation in the NCF1 gene was identified (see, e.g., <a href="#0003">608512.0003</a>-<a href="#0004">608512.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11133775" 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="#19" class="mim-tip-reference" title="Roos, D., de Boer, M., Yavuz Koker, M., Dekker, J., Singh-Gupta, V., Ahlin, A., Palmblad, J., Sanal, O., Kurenko-Deptuch, M., Jolles, S., Wolach, B. <strong>Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47-phox component of the phagocyte NADPH oxidase.</strong> Hum. Mutat. 27: 1218-1229, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16972229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16972229</a>] [<a href="https://doi.org/10.1002/humu.20413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16972229">Roos et al. (2006)</a> identified 7 different mutations and a large deletion in the NCF1 gene in affected individuals from 9 unrelated families with autosomal recessive CGD1. In 6 families, the patients were compound heterozygous for the common GT deletion and another pathogenic mutation. Patients from 2 families had a homozygous mutation, and a patient from 1 family was compound heterozygous for 2 mutations (see, e.g., <a href="#0005">608512.0005</a>-<a href="#0007">608512.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16972229" 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>Associations Pending Confirmation</em></strong></p><p>
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Williams-Beuren syndrome (WBS; <a href="/entry/194050">194050</a>), caused by a heterozygous deletion at 7q11.23, represents a model for studying hypertension, a leading risk factor for mortality worldwide, in a genetically determined disorder. Haploinsufficiency of the elastin gene (<a href="/entry/130160">130160</a>) is known to lead to the vascular stenoses in WBS and is also thought to predispose to hypertension, which is present in approximately 50% of WBS patients. <a href="#5" class="mim-tip-reference" title="Del Campo, M., Antonell, A., Magano, L. F., Munoz, F. J., Flores, R., Bayes, M., Perez Jurado, L. A. <strong>Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension.</strong> Am. J. Hum. Genet. 78: 533-542, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16532385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16532385</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16532385[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/10.1086/501073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16532385">Del Campo et al. (2006)</a> performed clinical and molecular characterization of 96 patients with WBS to explore clinical-molecular correlations. Deletion breakpoints were precisely defined and found to result in variability at 2 genes, NCF1 and GTF2IRD2 (<a href="/entry/608899">608899</a>). Hypertension was significantly less prevalent in patients with WBS who had a deletion that included NCF1 (p = 0.02), a gene encoding the p47(phox) subunit of NADPH oxidase. Decreased levels of the p47(phox) protein, decreased superoxide anion production, and lower protein nitrotyrosination were all observed in cell lines from patients hemizygous at NCF1. The results indicated that the loss of a functional copy of NCF1 protects a proportion of patients with WBS against hypertension, likely through a lifelong reduced angiotensin II (see <a href="/entry/106150">106150</a>)-mediated oxidative stress. <a href="#5" class="mim-tip-reference" title="Del Campo, M., Antonell, A., Magano, L. F., Munoz, F. J., Flores, R., Bayes, M., Perez Jurado, L. A. <strong>Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension.</strong> Am. J. Hum. Genet. 78: 533-542, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16532385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16532385</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16532385[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/10.1086/501073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16532385">Del Campo et al. (2006)</a> speculated that antioxidant therapy that reduces NADPH oxidase activity might have a benefit in identifiable patients with WBS in whom serious complications related to hypertension have been reported, as well as in forms of essential hypertension mediated by a similar pathogenic mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16532385" 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>For discussion of a possible association between variation in the NCF1 gene and susceptibility to systemic lupus erythematosus, see <a href="/entry/152700">152700</a>.</p>
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<p><a href="#3" class="mim-tip-reference" title="Clark, R. A., Malech, H. L., Gallin, J. I., Nunoi, H., Volpp, B. D., Pearson, D. W., Nauseef, W. M., Curnutte, J. T. <strong>Genetic variants of chronic granulomatous disease: prevalence of deficiencies of two cytosolic components of the NADPH oxidase system.</strong> New Eng. J. Med. 321: 647-652, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2770793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2770793</a>] [<a href="https://doi.org/10.1056/NEJM198909073211005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2770793">Clark et al. (1989)</a> concluded that an autosomal recessive form of chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>) due to deficiency of NCF1 represents about 33% of all cases; the autosomal form due to deficiency of NCF2 (<a href="/entry/608515">608515</a>) represents about 5% of cases (CGD2; <a href="/entry/233710">233710</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2770793" 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>Pristane-induced arthritis (PIA) in the highly susceptible DA strain of rat is characterized by sudden onset of arthritis 2 weeks after an intradermal injection of pristane followed by a chronic relapsing disease course with an erosive and symmetric destruction of peripheral joints and production of rheumatoid factors. Genetic segregation analyses of arthritis-susceptible and arthritis-resistant rats had shown linkage between arthritis and several different chromosomal regions. Different chromosome regions controlled different phases of the disease, such as the onset, severity during the acute phase, and severity of destruction in the chronic relapsing phase. Most of the loci were shared with other arthritis models and also with a chronic relapsing model of multiple sclerosis. One of these quantitative trait loci (QTLs), denoted Pia4, was found to be associated with arthritis severity and joint erosion during the entire disease course. In other strains of rats, the Pia4 region had been identified in models of multiple sclerosis and uveitis, indicating that Pia4 controls several inflammatory diseases and contains genes with a high degree of polymorphism. Pia4 may also correspond to the homologous locus on mouse chromosome 5 (Bbaa2) that was identified using a model of Borrelia-induced Lyme disease (<a href="#22" class="mim-tip-reference" title="Weis, J. J., McCracken, B. A., Ma, Y., Fairbairn, D., Roper, R. J., Morrison, T. B., Weis, J. H., Zachary, J. F., Doerge, R. W., Teuscher, C. <strong>Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease.</strong> J. Immun. 162: 948-956, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9916719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9916719</a>]" pmid="9916719">Weis et al., 1999</a>). <a href="#15" class="mim-tip-reference" title="Olofsson, P., Holmberg, J., Tordsson, J., Lu, S., Akerstrom, B., Holmdahl, R. <strong>Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.</strong> Nature Genet. 33: 25-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12461526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12461526</a>] [<a href="https://doi.org/10.1038/ng1058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12461526">Olofsson et al. (2003)</a> used positional cloning to demonstrate that the Pia4 QTL is a naturally occurring polymorphism of the Ncf1 gene. The disease-related allele of Ncf1 had reduced oxidative burst response and promoted activation of arthritogenic T cells. Pharmacologic treatment with substances that activate the NADPH oxidase complex ameliorated arthritis. Hence, Ncf1 is associated with a novel autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9916719+12461526" 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 examining a strain of mouse with a point mutation in the splice site for exon 8 of the Ncf1 gene, <a href="#10" class="mim-tip-reference" title="Hultqvist, M., Olofsson, P., Holmberg, J., Backstrom, B. T., Tordsson, J., Holmdahl, R. <strong>Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene.</strong> Proc. Nat. Acad. Sci. 101: 12646-12651, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15310853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15310853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15310853[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0403831101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15310853">Hultqvist et al. (2004)</a> found that the homozygous mutation led to reduced Ncf1 expression and undetectable reactive oxygen species (ROS) response. Mutated mice showed augmented severity of collagen-induced arthritis and chronic experimental autoimmune encephalomyelitis, and enhanced T cell-dependent autoimmunity. Female mice spontaneously developed severe arthritis in the postpartum period, a phase of life when both mice and humans are susceptible to developing certain autoimmune diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15310853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using mice with a naturally occurring Ncf1 mutation reported by <a href="#10" class="mim-tip-reference" title="Hultqvist, M., Olofsson, P., Holmberg, J., Backstrom, B. T., Tordsson, J., Holmdahl, R. <strong>Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene.</strong> Proc. Nat. Acad. Sci. 101: 12646-12651, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15310853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15310853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15310853[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0403831101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15310853">Hultqvist et al. (2004)</a> and rat type II collagen (CII), which, like human CII (COL2A1; <a href="/entry/120140">120140</a>), differs from the mouse sequence only at residue 266, <a href="#8" class="mim-tip-reference" title="Hagenow, K., Gelderman, K. A., Hultqvist, M., Merky, P., Backlund, J., Frey, O., Kamradt, T., Holmdahl, R. <strong>Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell-mediated adjuvant-free arthritis in mice.</strong> J. Immun. 183: 874-881, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19553535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19553535</a>] [<a href="https://doi.org/10.4049/jimmunol.0900966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19553535">Hagenow et al. (2009)</a> examined arthritis in a mouse model that did not require the use of adjuvant. Mutant mice produced lower levels of ROS, but increased levels of autoantibodies and greater numbers of T cells expressing Il33r (IL1RL1; <a href="/entry/601203">601203</a>). With impaired T-cell tolerance of tissue-specific CII, the mice developed severe arthritis. <a href="#8" class="mim-tip-reference" title="Hagenow, K., Gelderman, K. A., Hultqvist, M., Merky, P., Backlund, J., Frey, O., Kamradt, T., Holmdahl, R. <strong>Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell-mediated adjuvant-free arthritis in mice.</strong> J. Immun. 183: 874-881, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19553535/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19553535</a>] [<a href="https://doi.org/10.4049/jimmunol.0900966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19553535">Hagenow et al. (2009)</a> concluded that insufficient ROS production promotes breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL5 (<a href="/entry/147850">147850</a>)- and IL33R-dependent T-cell activation pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15310853+19553535" 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="#4" class="mim-tip-reference" title="Deffert, C., Schappi, M. G., Pache, J.-C., Cachat, J., Vesin, D., Bisig, R., Ma Mulone, X.., Kelkka, T., Holmdahl, R., Garcia, I., Olleros, M. L., Krause, K.-H. <strong>Bacillus Calmette-Guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.</strong> PLoS Pathog. 10: e1004325, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25188296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25188296</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25188296[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/10.1371/journal.ppat.1004325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25188296">Deffert et al. (2014)</a> conducted a literature search that found nearly 300 cases of mycobacterial infection in CGD, principally caused by M. bovis bacillus Calmette-Guerin (BCG). The authors then investigated BCG infection in 3 different mouse models of CGD: 2 strains of mice lacking Ncf1 and mice lacking Cybb. All 3 CGD mouse strains were highly susceptible to intravenous BCG infection, manifest as severe weight loss, hemorrhagic pneumonia with high numbers of neutrophils, and 50% mortality. These mice had only moderately increased bacterial load. Macrophage-specific rescue of Cybb restored BCG resistance. ROS was generated in granulomas of wildtype mice, but not CGD mice. Massive increases in the release of the cytokines Tnf (<a href="/entry/191160">191160</a>), Ifng, Il17, and Il12 (<a href="/entry/161561">161561</a>), as well as Cxcl1 (<a href="/entry/155730">155730</a>), a neutrophil chemoattractant, occurred early after infection in CGD mice, possibly explaining disease severity. Macrophages clustered in granulomas in wildtype mice, whereas macrophages were diffusely distributed in lungs of CGD mice. <a href="#4" class="mim-tip-reference" title="Deffert, C., Schappi, M. G., Pache, J.-C., Cachat, J., Vesin, D., Bisig, R., Ma Mulone, X.., Kelkka, T., Holmdahl, R., Garcia, I., Olleros, M. L., Krause, K.-H. <strong>Bacillus Calmette-Guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.</strong> PLoS Pathog. 10: e1004325, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25188296/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25188296</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25188296[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/10.1371/journal.ppat.1004325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25188296">Deffert et al. (2014)</a> concluded that lack of NADPH oxidase leads to markedly increased severity of BCG infection through increased cytokine production and reduced granuloma formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25188296" 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">rs4029402 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs4029402;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=rs4029402" 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=rs4029402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 unrelated cases of autosomal recessive chronic granulomatous disease-1 (CGD1; <a href="/entry/233700">233700</a>), <a href="#1" class="mim-tip-reference" title="Casimir, C. M., Bu-Ghanim, H. N., Rodaway, A. R. F., Bentley, D. L., Rowe, P., Segal, A. W. <strong>Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat.</strong> Proc. Nat. Acad. Sci. 88: 2753-2757, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2011585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2011585</a>] [<a href="https://doi.org/10.1073/pnas.88.7.2753" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2011585">Casimir et al. (1991)</a> identified a homozygous 2-bp deletion (c.75delGT) at a GTGT tandem repeat in the NCF1 gene, corresponding to the acceptor site of the first intron-exon junction (between IVS1 and exon 2). The authors suggested that slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2011585" 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 unrelated patients (KS and SR) with CGD, <a href="#20" class="mim-tip-reference" title="Volpp, B. D., Lin, Y. <strong>In vitro molecular reconstitution of the respiratory burst in B lymphoblasts from p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 91: 201-207, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7678602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7678602</a>] [<a href="https://doi.org/10.1172/JCI116171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7678602">Volpp and Lin (1993)</a> identified a c.75delGT mutation in the NCF1 gene, resulting in a frameshift and premature termination at base 165. Patient KS was homozygous for the GT deletion, which occurred within the sequence TATGTGTA (bases 70-78). The other patient (SR) was compound heterozygous for c.75delGT and a 1-bp deletion (c.502delG; <a href="#0002">608512.0002</a>), which results in a frameshift and premature termination at base 605. Patient SR had previously been reported by <a href="#2" class="mim-tip-reference" title="Clark, R. A., Klebanoff, S. J. <strong>Chronic granulomatous disease: studies of a family with impaired neutrophil chemotactic, metabolic and bactericidal function.</strong> Am. J. Med. 65: 941-948, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/742630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">742630</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90745-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="742630">Clark and Klebanoff (1978)</a>. <a href="#20" class="mim-tip-reference" title="Volpp, B. D., Lin, Y. <strong>In vitro molecular reconstitution of the respiratory burst in B lymphoblasts from p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 91: 201-207, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7678602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7678602</a>] [<a href="https://doi.org/10.1172/JCI116171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7678602">Volpp and Lin (1993)</a> demonstrated that the transfection of NCF1 cDNA into p47-phox-deficient cell lines resulted in the generation of normal levels of superoxide and readily detectable cytosolic enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=742630+7678602" 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="Gorlach, A., Lee, P. L., Roesler, J., Hopkins, P. J., Christensen, B., Green, E. D., Chanock, S. J., Curnutte, J. T. <strong>A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 100: 1907-1918, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9329953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9329953</a>] [<a href="https://doi.org/10.1172/JCI119721" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9329953">Gorlach et al. (1997)</a> found that in each of 34 consecutive unrelated normal individuals, both the normal and mutant delta-GT sequences were present in genomic DNA. Further study revealed that this finding was due to the p47-phox pseudogene containing the delta-GT mutation. This close linkage, together with the presence within each gene of multiple recombination hotspots, suggested that the predominance of the delta-GT mutation in this autosomal recessive form of CGD is caused by recombination events between the wildtype gene and the pseudogene(s). Gene conversion events between homologous genes and their pseudogenes had been described in the pathogenesis of several genetic disorders, such as 21-hydroxylase deficiency (<a href="/entry/201910">201910</a>), von Willebrand disease (<a href="/entry/193400">193400</a>), and Gaucher disease (<a href="/entry/230800">230800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9329953" 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="#17" class="mim-tip-reference" title="Roesler, J., Curnutte, J. T., Rae, J., Barrett, D., Patino, P., Chanock, S. J., Goerlach, A. <strong>Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease.</strong> Blood 95: 2150-2156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10706888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10706888</a>]" pmid="10706888">Roesler et al. (2000)</a> performed sequence analysis of 28 unrelated, racially diverse patients with the p47-phox-deficient form of CGD and 37 healthy individuals. In 25 patients, the CGD deletion in exon 2 was present in all alleles. Three patients and all healthy individuals contained GTGT and delta-GT sequences, the latter being a characteristic of the NCF1 pseudogene. A total of 22 patients carried additional pseudogene-specific intronic sequences on all alleles, either only in intron 1 or in intron 1 and intron 2, which led to different types of chimeric DNA strands. <a href="#17" class="mim-tip-reference" title="Roesler, J., Curnutte, J. T., Rae, J., Barrett, D., Patino, P., Chanock, S. J., Goerlach, A. <strong>Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease.</strong> Blood 95: 2150-2156, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10706888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10706888</a>]" pmid="10706888">Roesler et al. (2000)</a> concluded that recombination events between the NCF1 gene and its highly homologous pseudogenes result in the incorporation of delta-GT into the NCF1 gene, thereby leading to the high frequency of GT deletion in CGD patients with the p47-phox-deficient form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10706888" 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>Unlike other CGD subtypes, in which there is great heterogeneity among mutations, 97% of affected alleles in patients with p47-phox deficiency carry the 2-bp deletion in the NCF1 gene (<a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11133775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient (SR) with chronic granulomatous disease due to deficiency of p47-phox (CGD1; <a href="/entry/233700">233700</a>), <a href="#20" class="mim-tip-reference" title="Volpp, B. D., Lin, Y. <strong>In vitro molecular reconstitution of the respiratory burst in B lymphoblasts from p47-phox-deficient chronic granulomatous disease.</strong> J. Clin. Invest. 91: 201-207, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7678602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7678602</a>] [<a href="https://doi.org/10.1172/JCI116171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7678602">Volpp and Lin (1993)</a> found compound heterozygosity for 2 frameshift mutations in the NCF1 gene: a GT deletion (<a href="#0001">608512.0001</a>) and c.502delG. Both mutations resulted in an early stop codon. The patient had previously been reported by <a href="#2" class="mim-tip-reference" title="Clark, R. A., Klebanoff, S. J. <strong>Chronic granulomatous disease: studies of a family with impaired neutrophil chemotactic, metabolic and bactericidal function.</strong> Am. J. Med. 65: 941-948, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/742630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">742630</a>] [<a href="https://doi.org/10.1016/0002-9343(78)90745-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="742630">Clark and Klebanoff (1978)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=742630+7678602" 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> rs119103270 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103270;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/rs119103270?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=rs119103270" 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=rs119103270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with autosomal recessive chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>) lacking the usual GT deletion (<a href="#0001">608512.0001</a>), <a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al. (2001)</a> found compound heterozygosity for 2 other mutations in the NCF1 gene: a 125G-A transition exon 2 of the NCF1 gene on one allele, resulting in an arg42-to-gln (R42Q) substitution, and a deletion of G811 (<a href="#0004">608512.0004</a>) on the other, causing a frameshift at residue 271 and leading to a premature stop codon at residue 375. In another patient with CGD who was heterozygous for delGT, they found that the other allele carried the 125G-A mutation, predicting arg42 to gln. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11133775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunoprecipitation analysis, <a href="#12" class="mim-tip-reference" title="Kanai, F., Liu, H., Field, S. J., Akbary, H., Matsuo, T., Brown, G. E., Cantley, L. C., Yaffe, M. B. <strong>The PX domains of p47phox and p40phox bind to lipid products of PI(3)K.</strong> Nature Cell Biol. 3: 675-678, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11433300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11433300</a>] [<a href="https://doi.org/10.1038/35083070" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11433300">Kanai et al. (2001)</a> showed that the R42Q mutation in the PX domain of p47-phox eliminated phosphoinositide binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11433300" 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">rs1307080411 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1307080411;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=rs1307080411" 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=rs1307080411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 1-bp deletion in the NCF1 gene that was found in compound heterozygous state in a patient with autosomal recessive chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>) by <a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al. (2001)</a>, see <a href="#0003">608512.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11133775" 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">rs119103271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103271;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=rs119103271" 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=rs119103271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with autosomal recessive chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>), <a href="#19" class="mim-tip-reference" title="Roos, D., de Boer, M., Yavuz Koker, M., Dekker, J., Singh-Gupta, V., Ahlin, A., Palmblad, J., Sanal, O., Kurenko-Deptuch, M., Jolles, S., Wolach, B. <strong>Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47-phox component of the phagocyte NADPH oxidase.</strong> Hum. Mutat. 27: 1218-1229, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16972229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16972229</a>] [<a href="https://doi.org/10.1002/humu.20413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16972229">Roos et al. (2006)</a> identified compound heterozygosity for 2 mutations in the NCF1 gene: the common 2-bp deletion (<a href="#0001">608512.0001</a>) and a 271C-T transition, resulting in a gln91-to-ter (Q91X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16972229" 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> rs119103272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103272;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/rs119103272?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=rs119103272" 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=rs119103272" 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=RCV000002342" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002342" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002342</a>
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<p>In affected members of a family with autosomal recessive chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>), <a href="#19" class="mim-tip-reference" title="Roos, D., de Boer, M., Yavuz Koker, M., Dekker, J., Singh-Gupta, V., Ahlin, A., Palmblad, J., Sanal, O., Kurenko-Deptuch, M., Jolles, S., Wolach, B. <strong>Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47-phox component of the phagocyte NADPH oxidase.</strong> Hum. Mutat. 27: 1218-1229, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16972229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16972229</a>] [<a href="https://doi.org/10.1002/humu.20413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16972229">Roos et al. (2006)</a> identified compound heterozygosity for 2 mutations in the NCF1 gene: the common 2-bp deletion (<a href="#0001">608512.0001</a>) and a 333T-A transversion, resulting in a cys111-to-ter (C111X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16972229" 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> rs119103273 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119103273;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/rs119103273?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=rs119103273" 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=rs119103273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with autosomal recessive chronic granulomatous disease (CGD1; <a href="/entry/233700">233700</a>), <a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al. (2001)</a> identified a 574G-A transition at the end of exon 6 of the NCF1 gene, predicted to result in a gly192-to-ser (G192S) substitution. PCR analysis suggested homozygosity, but allele-specific PCR was not possible due to insufficient DNA. <a href="#14" class="mim-tip-reference" title="Noack, D., Rae, J., Cross, A. R., Ellis, B. A., Newburger, P. E., Curnutte, J. T., Heyworth, P. G. <strong>Autosomal recessive chronic granulomatous disease caused by defects in NCF1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF1 pseudogenes.</strong> Blood 97: 305-311, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11133775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11133775</a>] [<a href="https://doi.org/10.1182/blood.v97.1.305" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11133775">Noack et al. (2001)</a> suggested that aberrant splicing during processing of the RNA transcript is the primary cause of p47-phox deficiency in this patient rather than protein instability resulting from the G192S substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11133775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 presumably unrelated consanguineous Turkish families with autosomal recessive CGD, <a href="#19" class="mim-tip-reference" title="Roos, D., de Boer, M., Yavuz Koker, M., Dekker, J., Singh-Gupta, V., Ahlin, A., Palmblad, J., Sanal, O., Kurenko-Deptuch, M., Jolles, S., Wolach, B. <strong>Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47-phox component of the phagocyte NADPH oxidase.</strong> Hum. Mutat. 27: 1218-1229, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16972229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16972229</a>] [<a href="https://doi.org/10.1002/humu.20413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16972229">Roos et al. (2006)</a> identified homozygosity for the 574G-A transition. Further analysis showed that the mutation resulted in aberrant splicing of exons 6 and 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16972229" 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://doi.org/10.1371/journal.ppat.1004325" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ni1096" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.272.28.17802" target="_blank">Full Text</a>]
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Roesler, J., Curnutte, J. T., Rae, J., Barrett, D., Patino, P., Chanock, S. J., Goerlach, A.
|
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<strong>Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease.</strong>
|
|
Blood 95: 2150-2156, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10706888/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10706888</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10706888" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Romani2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Romani, L., Fallarino, F., De Luca, A., Montagnoli, C., D'Angelo, C., Zelante, T., Vacca, C., Bistoni, F., Fioretti, M. C., Grohmann, U., Segal, B. H., Puccetti, P.
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<strong>Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.</strong>
|
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Nature 451: 211-215, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18185592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18185592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18185592" 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/nature06471" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Roos2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Roos, D., de Boer, M., Yavuz Koker, M., Dekker, J., Singh-Gupta, V., Ahlin, A., Palmblad, J., Sanal, O., Kurenko-Deptuch, M., Jolles, S., Wolach, B.
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|
<strong>Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47-phox component of the phagocyte NADPH oxidase.</strong>
|
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Hum. Mutat. 27: 1218-1229, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16972229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16972229</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16972229" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.20413" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Volpp1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Volpp, B. D., Lin, Y.
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<strong>In vitro molecular reconstitution of the respiratory burst in B lymphoblasts from p47-phox-deficient chronic granulomatous disease.</strong>
|
|
J. Clin. Invest. 91: 201-207, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7678602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7678602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7678602" 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/10.1172/JCI116171" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Volpp1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Volpp, B. D., Nauseef, W. M., Donelson, J. E., Moser, D. R., Clark, R. A.
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<strong>Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 7195-7199, 1989. Note: Erratum: Proc. Nat. Acad. Sci. 86: 9563 only, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2550933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2550933</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2550933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.86.18.7195" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Weis1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weis, J. J., McCracken, B. A., Ma, Y., Fairbairn, D., Roper, R. J., Morrison, T. B., Weis, J. H., Zachary, J. F., Doerge, R. W., Teuscher, C.
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<strong>Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease.</strong>
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J. Immun. 162: 948-956, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9916719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9916719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9916719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</ol>
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<br />
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 07/23/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse - updated : 10/1/2014<br>Paul J. Converse - updated : 8/14/2013<br>Paul J. Converse - updated : 11/3/2010<br>Ada Hamosh - updated : 1/23/2008<br>Cassandra L. Kniffin - updated : 12/29/2006<br>Victor A. McKusick - updated : 3/15/2006<br>Patricia A. Hartz - updated : 12/7/2005<br>Paul J. Converse - updated : 10/27/2005
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 3/8/2004
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 07/28/2020
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</span>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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ckniffin : 07/23/2020<br>carol : 07/07/2020<br>carol : 07/06/2020<br>ckniffin : 07/02/2020<br>carol : 04/27/2017<br>carol : 04/26/2017<br>alopez : 04/25/2017<br>mcolton : 07/21/2015<br>alopez : 2/9/2015<br>mgross : 10/3/2014<br>mcolton : 10/1/2014<br>mgross : 8/14/2013<br>mgross : 4/1/2013<br>terry : 3/28/2013<br>mgross : 7/7/2011<br>mgross : 11/4/2010<br>mgross : 11/4/2010<br>terry : 11/3/2010<br>alopez : 2/4/2008<br>terry : 1/23/2008<br>wwang : 1/2/2007<br>ckniffin : 12/29/2006<br>alopez : 3/20/2006<br>terry : 3/15/2006<br>wwang : 12/9/2005<br>terry : 12/7/2005<br>mgross : 11/7/2005<br>terry : 10/27/2005<br>carol : 3/12/2004<br>terry : 3/12/2004<br>ckniffin : 3/11/2004
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</span>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608512
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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NEUTROPHIL CYTOSOLIC FACTOR 1; NCF1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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<div>
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<h4>
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<span class="mim-font">
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NOXO2<br />
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p47-PHOX
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: NCF1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 7q11.23
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:74,774,011-74,789,315 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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7q11.23
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</span>
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</td>
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<td>
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<span class="mim-font">
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Chronic granulomatous disease 1, autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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233700
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Neutrophil cytosolic factor-1 (NCF1), also known as p47-phox (for phagocyte oxidase), is a component of the NADPH oxidase complex (Volpp et al., 1989). </p>
|
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</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By screening a promyelocytic leukemia cDNA library, Volpp et al. (1989) cloned and sequenced a cDNA encoding the 47-kD component of the NADPH oxidase system. The 390-amino acid protein has an N-terminal glycine residue, which may serve to translocate the protein to the plasma membrane, several phosphorylation sites, a potential nucleotide-binding site, and a region of homology to some protein kinases. </p><p>Rodaway et al. (1990) isolated and characterized a full-length cDNA clone for neutrophil cytosolic factor-1. An antiserum raised against the predicted C terminus of the protein detected a 47-kD polypeptide that is present in normal neutrophils, but not in those from patients with autosomal chronic granulomatous disease (CGD1; 233700). The protein is associated with the vacuolar membrane and is phosphorylated in response to phorbol ester treatment. Gene expression was limited to 3 cell types: granulocytes, monocytes, and B lymphocytes. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To study the cis elements and trans-acting factors responsible for p47-phox expression, Li et al. (1997) cloned and characterized the p47-phox promoter. A predominant transcriptional start site was identified 21 nucleotides upstream of the translation initiation codon. Transient transfections of HL60 human myeloid cells were performed with a series of 5-prime-deletion p47-phox-luciferase reporter constructs to identify the gene promoter sequences. The -224 and -86 constructs had the strongest p47-phox promoter activity, whereas the -46 construct showed a major reduction in activity and the -36 construct a complete loss of activity. DNase I footprint analysis identified a protected region from -37 to -53. This region containing a consensus PU.1 (165170) site bound specifically both PU.1 present in nuclear extracts and PU.1 synthesized in vitro. Mutations of this site eliminated PU.1 binding and abolished the ability of the p47-phox promoter to direct expression of the reporter gene. Li et al. (1997) concluded that p47-phox promoter activity requires PU.1. </p>
|
|
</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Volpp et al. (1989) found that, in a cell-free NADPH oxidase system, fusion p47-phox proteins augmented superoxide generation and reconstituted the cytosolic defect of a patient with autosomal chronic granulomatous disease type I (233700) who was missing the p47-phox protein. </p><p>Using immunoprecipitation analysis, Kanai et al. (2001) showed that mutation of arg57 in the PX domain of p40-phox (NCF4; 601488) or of the analogous residue, arg42, in p47-phox eliminated phosphoinositide binding. Mutation of arg90 in p47-phox markedly reduced, but did not eliminate, phosphoinositide binding. Kanai et al. (2001) concluded that PX domains are specific phosphoinositide-binding modules and that different PX domains have different phosphoinositide specificities. </p><p>Jackson et al. (2004) reported that activated mouse T cells deficient in either gp91-phox (CYBB; 300481) or p47-phox showed enhanced activation of Erk (see MAPK3; 601795) and Mek (see MAP2K1; 176872), diminished expression of phagocyte-type NADPH oxidase, and a relative increase in Th1-type cytokine secretion. They suggested that similar alterations may be found in patients with chronic granulomatous disease. </p><p>During inflammation, indoleamine 2,3-dioxygenase (IDO; 147435) is upregulated in dendritic cells and phagocytes by proinflammatory stimuli, most notably, interferon-gamma (IFNG; 147570), and the enzyme then uses superoxide as a 'cofactor' for oxidative cleavage of the indole ring of tryptophan, yielding an intermediate that deformylates to L-kynurenine. Romani et al. (2008) demonstrated that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in p47-deficient CGD mice with lethal pulmonary aspergillosis (see 614079), leading to unrestrained V-gamma-1+ gamma-delta T-cell reactivity, dominant production of interleukin-17 (IL17; 603149), defective regulatory T-cell activity, and acute inflammatory lung injury. Although beneficial effects are induced by IL17 neutralization or gamma-delta T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes coadministration of recombinant IFNG, restores production of downstream immunoactive metabolites and enables the emergence of regulatory V-gamma-4+ gamma-delta and Foxp3+ (300292) alpha-beta T cells. Therefore, Romani et al. (2008) concluded that paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hsieh et al. (1989) concluded from Southern blot analysis of hybrid cell DNAs that the NCF1 gene is located on chromosome 10; however, by Southern analysis of somatic cell hybrid lines and chromosomal in situ hybridization, Francke et al. (1990) assigned the NCF1 gene to 7q11.23. </p><p><strong><em>Pseudogenes</em></strong></p><p>
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|
Gorlach et al. (1997) identified a highly homologous p47-phox pseudogene which colocalized with the NCF1 gene to 7q11.23. The localization of the pseudogene was determined by analyzing DNA from a panel of human/hamster hybrid cell lines and of a YAC library highly enriched for chromosome 7. This was an unprocessed type of pseudogene, which presumably arose by gene duplication. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Chronic Granulomatous Disease, Autosomal Recessive, 1</em></strong></p><p>
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In 3 unrelated patients with autosomal recessive CGD1, Casimir et al. (1991) identified a homozygous 2-bp deletion in the NCF1 gene (608512.0001). Casimir et al. (1991) stated that about 30% of CGD cases are autosomal recessive and that more than 90% of the autosomal recessive cases have a defect in the 47-kD cytosolic protein. Gorlach et al. (1997) reported that the 2-bp mutation is carried in a closely linked pseudogene(s) and suggested that the gene mutation is caused by homologous recombination between the wildtype and pseudogene(s). </p><p>Unlike other CGD subtypes, in which there is great heterogeneity among mutations, 97% of affected alleles in patients with p47-phox deficiency carry the 2-bp deletion in the NCF1 gene (Noack et al., 2001). This unusually high incidence results from recombination events between NCF1 and its highly homologous pseudogenes which carry the deletion. Of 50 consecutive patients with CGD due to deficiency of NCF1, Noack et al. (2001) identified 4 who were heterozygous for the GT deletion as well as 2 whose DNA appeared normal at this position. In each of the 4 patients who were heterozygous for the GT deletion, an additional novel mutation in the NCF1 gene was identified (see, e.g., 608512.0003-608512.0004). </p><p>Roos et al. (2006) identified 7 different mutations and a large deletion in the NCF1 gene in affected individuals from 9 unrelated families with autosomal recessive CGD1. In 6 families, the patients were compound heterozygous for the common GT deletion and another pathogenic mutation. Patients from 2 families had a homozygous mutation, and a patient from 1 family was compound heterozygous for 2 mutations (see, e.g., 608512.0005-608512.0007). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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|
Williams-Beuren syndrome (WBS; 194050), caused by a heterozygous deletion at 7q11.23, represents a model for studying hypertension, a leading risk factor for mortality worldwide, in a genetically determined disorder. Haploinsufficiency of the elastin gene (130160) is known to lead to the vascular stenoses in WBS and is also thought to predispose to hypertension, which is present in approximately 50% of WBS patients. Del Campo et al. (2006) performed clinical and molecular characterization of 96 patients with WBS to explore clinical-molecular correlations. Deletion breakpoints were precisely defined and found to result in variability at 2 genes, NCF1 and GTF2IRD2 (608899). Hypertension was significantly less prevalent in patients with WBS who had a deletion that included NCF1 (p = 0.02), a gene encoding the p47(phox) subunit of NADPH oxidase. Decreased levels of the p47(phox) protein, decreased superoxide anion production, and lower protein nitrotyrosination were all observed in cell lines from patients hemizygous at NCF1. The results indicated that the loss of a functional copy of NCF1 protects a proportion of patients with WBS against hypertension, likely through a lifelong reduced angiotensin II (see 106150)-mediated oxidative stress. Del Campo et al. (2006) speculated that antioxidant therapy that reduces NADPH oxidase activity might have a benefit in identifiable patients with WBS in whom serious complications related to hypertension have been reported, as well as in forms of essential hypertension mediated by a similar pathogenic mechanism. </p><p>For discussion of a possible association between variation in the NCF1 gene and susceptibility to systemic lupus erythematosus, see 152700.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Clark et al. (1989) concluded that an autosomal recessive form of chronic granulomatous disease (CGD1; 233700) due to deficiency of NCF1 represents about 33% of all cases; the autosomal form due to deficiency of NCF2 (608515) represents about 5% of cases (CGD2; 233710). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Pristane-induced arthritis (PIA) in the highly susceptible DA strain of rat is characterized by sudden onset of arthritis 2 weeks after an intradermal injection of pristane followed by a chronic relapsing disease course with an erosive and symmetric destruction of peripheral joints and production of rheumatoid factors. Genetic segregation analyses of arthritis-susceptible and arthritis-resistant rats had shown linkage between arthritis and several different chromosomal regions. Different chromosome regions controlled different phases of the disease, such as the onset, severity during the acute phase, and severity of destruction in the chronic relapsing phase. Most of the loci were shared with other arthritis models and also with a chronic relapsing model of multiple sclerosis. One of these quantitative trait loci (QTLs), denoted Pia4, was found to be associated with arthritis severity and joint erosion during the entire disease course. In other strains of rats, the Pia4 region had been identified in models of multiple sclerosis and uveitis, indicating that Pia4 controls several inflammatory diseases and contains genes with a high degree of polymorphism. Pia4 may also correspond to the homologous locus on mouse chromosome 5 (Bbaa2) that was identified using a model of Borrelia-induced Lyme disease (Weis et al., 1999). Olofsson et al. (2003) used positional cloning to demonstrate that the Pia4 QTL is a naturally occurring polymorphism of the Ncf1 gene. The disease-related allele of Ncf1 had reduced oxidative burst response and promoted activation of arthritogenic T cells. Pharmacologic treatment with substances that activate the NADPH oxidase complex ameliorated arthritis. Hence, Ncf1 is associated with a novel autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans. </p><p>By examining a strain of mouse with a point mutation in the splice site for exon 8 of the Ncf1 gene, Hultqvist et al. (2004) found that the homozygous mutation led to reduced Ncf1 expression and undetectable reactive oxygen species (ROS) response. Mutated mice showed augmented severity of collagen-induced arthritis and chronic experimental autoimmune encephalomyelitis, and enhanced T cell-dependent autoimmunity. Female mice spontaneously developed severe arthritis in the postpartum period, a phase of life when both mice and humans are susceptible to developing certain autoimmune diseases. </p><p>Using mice with a naturally occurring Ncf1 mutation reported by Hultqvist et al. (2004) and rat type II collagen (CII), which, like human CII (COL2A1; 120140), differs from the mouse sequence only at residue 266, Hagenow et al. (2009) examined arthritis in a mouse model that did not require the use of adjuvant. Mutant mice produced lower levels of ROS, but increased levels of autoantibodies and greater numbers of T cells expressing Il33r (IL1RL1; 601203). With impaired T-cell tolerance of tissue-specific CII, the mice developed severe arthritis. Hagenow et al. (2009) concluded that insufficient ROS production promotes breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL5 (147850)- and IL33R-dependent T-cell activation pathway. </p><p>Deffert et al. (2014) conducted a literature search that found nearly 300 cases of mycobacterial infection in CGD, principally caused by M. bovis bacillus Calmette-Guerin (BCG). The authors then investigated BCG infection in 3 different mouse models of CGD: 2 strains of mice lacking Ncf1 and mice lacking Cybb. All 3 CGD mouse strains were highly susceptible to intravenous BCG infection, manifest as severe weight loss, hemorrhagic pneumonia with high numbers of neutrophils, and 50% mortality. These mice had only moderately increased bacterial load. Macrophage-specific rescue of Cybb restored BCG resistance. ROS was generated in granulomas of wildtype mice, but not CGD mice. Massive increases in the release of the cytokines Tnf (191160), Ifng, Il17, and Il12 (161561), as well as Cxcl1 (155730), a neutrophil chemoattractant, occurred early after infection in CGD mice, possibly explaining disease severity. Macrophages clustered in granulomas in wildtype mice, whereas macrophages were diffusely distributed in lungs of CGD mice. Deffert et al. (2014) concluded that lack of NADPH oxidase leads to markedly increased severity of BCG infection through increased cytokine production and reduced granuloma formation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>7 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0001 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</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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NCF1, 2-BP DEL, 75GT
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<br />
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SNP: rs4029402,
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ClinVar: RCV000002337, RCV001090891, RCV002283438
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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 3 unrelated cases of autosomal recessive chronic granulomatous disease-1 (CGD1; 233700), Casimir et al. (1991) identified a homozygous 2-bp deletion (c.75delGT) at a GTGT tandem repeat in the NCF1 gene, corresponding to the acceptor site of the first intron-exon junction (between IVS1 and exon 2). The authors suggested that slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene. </p><p>In 2 unrelated patients (KS and SR) with CGD, Volpp and Lin (1993) identified a c.75delGT mutation in the NCF1 gene, resulting in a frameshift and premature termination at base 165. Patient KS was homozygous for the GT deletion, which occurred within the sequence TATGTGTA (bases 70-78). The other patient (SR) was compound heterozygous for c.75delGT and a 1-bp deletion (c.502delG; 608512.0002), which results in a frameshift and premature termination at base 605. Patient SR had previously been reported by Clark and Klebanoff (1978). Volpp and Lin (1993) demonstrated that the transfection of NCF1 cDNA into p47-phox-deficient cell lines resulted in the generation of normal levels of superoxide and readily detectable cytosolic enzyme. </p><p>Gorlach et al. (1997) found that in each of 34 consecutive unrelated normal individuals, both the normal and mutant delta-GT sequences were present in genomic DNA. Further study revealed that this finding was due to the p47-phox pseudogene containing the delta-GT mutation. This close linkage, together with the presence within each gene of multiple recombination hotspots, suggested that the predominance of the delta-GT mutation in this autosomal recessive form of CGD is caused by recombination events between the wildtype gene and the pseudogene(s). Gene conversion events between homologous genes and their pseudogenes had been described in the pathogenesis of several genetic disorders, such as 21-hydroxylase deficiency (201910), von Willebrand disease (193400), and Gaucher disease (230800). </p><p>Roesler et al. (2000) performed sequence analysis of 28 unrelated, racially diverse patients with the p47-phox-deficient form of CGD and 37 healthy individuals. In 25 patients, the CGD deletion in exon 2 was present in all alleles. Three patients and all healthy individuals contained GTGT and delta-GT sequences, the latter being a characteristic of the NCF1 pseudogene. A total of 22 patients carried additional pseudogene-specific intronic sequences on all alleles, either only in intron 1 or in intron 1 and intron 2, which led to different types of chimeric DNA strands. Roesler et al. (2000) concluded that recombination events between the NCF1 gene and its highly homologous pseudogenes result in the incorporation of delta-GT into the NCF1 gene, thereby leading to the high frequency of GT deletion in CGD patients with the p47-phox-deficient form. </p><p>Unlike other CGD subtypes, in which there is great heterogeneity among mutations, 97% of affected alleles in patients with p47-phox deficiency carry the 2-bp deletion in the NCF1 gene (Noack et al., 2001). </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
NCF1, 1-BP DEL, 502G
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|
|
<br />
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|
|
SNP: rs1563003964,
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|
|
ClinVar: RCV000002338
|
|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (SR) with chronic granulomatous disease due to deficiency of p47-phox (CGD1; 233700), Volpp and Lin (1993) found compound heterozygosity for 2 frameshift mutations in the NCF1 gene: a GT deletion (608512.0001) and c.502delG. Both mutations resulted in an early stop codon. The patient had previously been reported by Clark and Klebanoff (1978). </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>.0003 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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|
NCF1, ARG42GLN
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<br />
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|
|
SNP: rs119103270,
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|
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gnomAD: rs119103270,
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|
|
ClinVar: RCV000002339, RCV001557272
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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 patient with autosomal recessive chronic granulomatous disease (CGD1; 233700) lacking the usual GT deletion (608512.0001), Noack et al. (2001) found compound heterozygosity for 2 other mutations in the NCF1 gene: a 125G-A transition exon 2 of the NCF1 gene on one allele, resulting in an arg42-to-gln (R42Q) substitution, and a deletion of G811 (608512.0004) on the other, causing a frameshift at residue 271 and leading to a premature stop codon at residue 375. In another patient with CGD who was heterozygous for delGT, they found that the other allele carried the 125G-A mutation, predicting arg42 to gln. </p><p>Using immunoprecipitation analysis, Kanai et al. (2001) showed that the R42Q mutation in the PX domain of p47-phox eliminated phosphoinositide binding. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
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|
</div>
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|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
NCF1, 1-BP DEL, NT811
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|
|
<br />
|
|
|
|
SNP: rs1307080411,
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|
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|
|
ClinVar: RCV000002340
|
|
|
|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the NCF1 gene that was found in compound heterozygous state in a patient with autosomal recessive chronic granulomatous disease (CGD1; 233700) by Noack et al. (2001), see 608512.0003. </p>
|
|
</span>
|
|
</div>
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|
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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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|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
NCF1, GLN91TER
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|
<br />
|
|
|
|
SNP: rs119103271,
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|
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|
|
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|
|
ClinVar: RCV000002341
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|
|
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with autosomal recessive chronic granulomatous disease (CGD1; 233700), Roos et al. (2006) identified compound heterozygosity for 2 mutations in the NCF1 gene: the common 2-bp deletion (608512.0001) and a 271C-T transition, resulting in a gln91-to-ter (Q91X) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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NCF1, CYS111TER
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<br />
|
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|
|
SNP: rs119103272,
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|
|
|
gnomAD: rs119103272,
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|
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ClinVar: RCV000002342
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal recessive chronic granulomatous disease (CGD1; 233700), Roos et al. (2006) identified compound heterozygosity for 2 mutations in the NCF1 gene: the common 2-bp deletion (608512.0001) and a 333T-A transversion, resulting in a cys111-to-ter (C111X) substitution. </p>
|
|
</span>
|
|
</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>.0007 GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 1</strong>
|
|
</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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NCF1, GLY192SER
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<br />
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|
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SNP: rs119103273,
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gnomAD: rs119103273,
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ClinVar: RCV000002343
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</span>
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<p>In a patient with autosomal recessive chronic granulomatous disease (CGD1; 233700), Noack et al. (2001) identified a 574G-A transition at the end of exon 6 of the NCF1 gene, predicted to result in a gly192-to-ser (G192S) substitution. PCR analysis suggested homozygosity, but allele-specific PCR was not possible due to insufficient DNA. Noack et al. (2001) suggested that aberrant splicing during processing of the RNA transcript is the primary cause of p47-phox deficiency in this patient rather than protein instability resulting from the G192S substitution. </p><p>In affected members of 2 presumably unrelated consanguineous Turkish families with autosomal recessive CGD, Roos et al. (2006) identified homozygosity for the 574G-A transition. Further analysis showed that the mutation resulted in aberrant splicing of exons 6 and 7. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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Cassandra L. Kniffin - updated : 07/23/2020<br>Paul J. Converse - updated : 10/1/2014<br>Paul J. Converse - updated : 8/14/2013<br>Paul J. Converse - updated : 11/3/2010<br>Ada Hamosh - updated : 1/23/2008<br>Cassandra L. Kniffin - updated : 12/29/2006<br>Victor A. McKusick - updated : 3/15/2006<br>Patricia A. Hartz - updated : 12/7/2005<br>Paul J. Converse - updated : 10/27/2005
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