3542 lines
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Entry
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- *604982 - HPS1 BIOGENESIS OF LYSOSOMAL ORGANELLES COMPLEX 3, SUBUNIT 1; HPS1
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- OMIM
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<p>
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<span class="h4">*604982</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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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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<li role="presentation">
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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/604982">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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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000107521;t=ENST00000361490" 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=3257" 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=604982" 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=ENSG00000107521;t=ENST00000361490" 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_000195,NM_001311345,NM_001322476,NM_001322477,NM_001322478,NM_001322479,NM_001322480,NM_001322481,NM_001322482,NM_001322483,NM_001322484,NM_001322485,NM_001322487,NM_001322489,NM_001322490,NM_001322491,NM_001322492,NM_182639,XM_005269757,XM_017016173,XM_047425146,XM_047425147,XM_047425148,XM_047425149,XM_047425150,XM_047425151,XM_047425152,XR_001747098,XR_007061961" 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_000195" 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=604982" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=05403&isoform_id=05403_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/HPS1" 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/1654351,2454273,12652845,17980675,33286414,33286416,52545818,68067891,119570262,119570263,119570264,119570265,119570266,119570267,119570268,194381368,530393540,914101166,957949540,957949543,957949546,957949549,957949552,957949555,957949558,957949561,957949565,1017029405,1017029419,1017029434,1017029436,1017029460,1017029475,1017029482,1017029509,1017029511,1017029517,1017029522,1017029529,1017029534,1017029536,1017029540,1034568028,1134667086,2217276960,2217276962,2217276964,2217276966,2217276968,2217276970,2217276972,2462518856,2462518858,2462518860,2462518862,2462518864,2462518866,2462518868,2462518870" 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/Q92902" 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=3257" 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=ENSG00000107521;t=ENST00000361490" 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=HPS1" 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=HPS1" 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+3257" 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/HPS1" 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:3257" 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/3257" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr10&hgg_gene=ENST00000699159.1&hgg_start=98413948&hgg_end=98446935&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:5163" 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://search.clinicalgenome.org/kb/genes/HGNC:5163" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/hps1" 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=604982[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=604982[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/HPS1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000107521" 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=HPS1" 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=HPS1" 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=HPS1" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://albinismdb.med.umn.edu/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Albinism Database</a></div><div style="margin-left: 0.5em;"><a href="http://www.retina-international.org/files/sci-news/epmut.htm" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the ep-Gene</a></div><div style="margin-left: 0.5em;"><a href="http://www.retina-international.org/files/sci-news/hpsmut.htm" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the HPS Gene</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HPS1&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/PA35101" 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:5163" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0033973.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2177763" 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/HPS1#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:2177763" 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/3257/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=3257" 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-051113-152" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:604982" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=HPS1&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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604982
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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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HPS1 BIOGENESIS OF LYSOSOMAL ORGANELLES COMPLEX 3, SUBUNIT 1; HPS1
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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>
|
|
<span class="mim-font">
|
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HPS1 GENE<br />
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PALE EAR, MOUSE, HOMOLOG OF
|
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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=HPS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HPS1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/10/461?start=-3&limit=10&highlight=461">10q24.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:98413948-98446935&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">10:98,413,948-98,446,935</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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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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<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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<p><a href="#8" class="mim-tip-reference" title="Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A. <strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong> Nature Genet. 14: 300-306, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>] [<a href="https://doi.org/10.1038/ng1196-300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896559">Oh et al. (1996)</a> identified the HPS1 gene by positional cloning. The HPS1 gene encodes a novel transmembrane protein that is thought to be a component of multiple cytoplasmic organelles and is apparently crucial for their normal development and function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896559" 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="#12" class="mim-tip-reference" title="Wildenberg, S. C., Fryer, J. P., Gardner, J. M., Oetting, W. S., Brilliant, M. H., King, R. A. <strong>Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.</strong> J. Invest. Derm. 110: 777-781, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9579545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9579545</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00183.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9579545">Wildenberg et al. (1998)</a> demonstrated an apparent alternative transcript of the HPS1 gene. By RT-PCR and Northern blot analysis, 2 polyadenylated transcripts were found in normal human melanocytes, human bone marrow cells, human melanoma cells, lymphoblastoid cell lines, and megakaryocytic leukemia cells. Thus, the HPS1 gene is complex and may have more than 1 biologically active transcript. <a href="#12" class="mim-tip-reference" title="Wildenberg, S. C., Fryer, J. P., Gardner, J. M., Oetting, W. S., Brilliant, M. H., King, R. A. <strong>Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.</strong> J. Invest. Derm. 110: 777-781, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9579545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9579545</a>] [<a href="https://doi.org/10.1046/j.1523-1747.1998.00183.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9579545">Wildenberg et al. (1998)</a> noted that the same type of alternative splicing occurs in the IGHM gene (<a href="/entry/147020">147020</a>), resulting in membrane-bound and secreted protein products. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9579545" 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="#7" class="mim-tip-reference" title="Martina, J. A., Moriyama, K., Bonifacino, J. S. <strong>BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4.</strong> J. Biol. Chem. 278: 29376-29384, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12756248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12756248</a>] [<a href="https://doi.org/10.1074/jbc.M301294200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12756248">Martina et al. (2003)</a> determined that HPS1 and HPS4 (<a href="/entry/606682">606682</a>) form a lysosomal complex that they termed BLOC3 (biogenesis of lysosome-related organelles complex-3). Coimmunoprecipitation experiments demonstrated that epitope-tagged and endogenous HPS1 and HPS4 proteins assembled with each other in vivo. The complex was predominantly cytosolic, with a small amount peripherally associated with membranes. Size exclusion chromatography and sedimentation velocity analysis of the cytosolic fraction indicated that HPS1 and HPS4 formed a moderately asymmetric complex with a molecular mass of about 175 kD. Hps4-deficient fibroblasts from light ear mice displayed normal distribution and trafficking of a lysosomal protein and an apparently normal accumulation of Zn(2+) in intracellular vesicles. In contrast, fibroblasts of AP3 (see AP3B1; <a href="/entry/603401">603401</a>)-deficient pearl mice showed deficits in both of these measures. <a href="#7" class="mim-tip-reference" title="Martina, J. A., Moriyama, K., Bonifacino, J. S. <strong>BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4.</strong> J. Biol. Chem. 278: 29376-29384, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12756248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12756248</a>] [<a href="https://doi.org/10.1074/jbc.M301294200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12756248">Martina et al. (2003)</a> concluded that HPS1 and HPS4 are components of a cytosolic complex that is involved in the biogenesis of lysosomal-related organelles through a mechanism distinct from that operated by the AP3 complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12756248" 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="#3" class="mim-tip-reference" title="Fukai, K., Oh, J., Frenk, E., Almodovar, C., Spritz, R. A. <strong>Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.</strong> Hum. Molec. Genet. 4: 1665-1669, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541858</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1665" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541858">Fukai et al. (1995)</a> used the linkage disequilibrium mapping approach to localize the HPS1 locus in 2 groups in whom the Hermansky-Pudlak syndrome (<a href="/entry/203300">203300</a>) is particularly frequent: a group in Puerto Rico and a group in an isolated village in the Swiss Alps. They localized the HPS1 locus in both groups to a 0.6-cM interval in chromosome segment 10q23.1-q23.2. <a href="#13" class="mim-tip-reference" title="Wildenberg, S. C., Oetting, W. S., Almodovar, C., Krumwiede, M., White, J. G., King, R. A. <strong>A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2.</strong> Am. J. Hum. Genet. 57: 755-765, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573033</a>]" pmid="7573033">Wildenberg et al. (1995)</a> likewise mapped the HPS1 locus to 10q. They collected blood samples from a relatively homogeneous population in Puerto Rico, where Hermansky-Pudlak syndrome has a frequency of about 1 in 1,800, giving a carrier frequency estimated to be 1 in 21. Analysis of pooled DNA samples allowed them to screen the genome rapidly for candidate loci and identify linkage with a marker on 10q. The result was verified with additional markers, and a maximum lod score of 5.07 at theta = 0.001 was calculated for marker D10S198. Haplotype analysis placed the HPS1 locus in a region of approximately 1 cM that contains the markers D10S198 and D10S1239. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7573033+8541858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A. <strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong> Nature Genet. 14: 300-306, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>] [<a href="https://doi.org/10.1038/ng1196-300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896559">Oh et al. (1996)</a> identified homozygous frameshifts in the HPS1 gene in Puerto Rican, Swiss, Irish, and Japanese patients with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A. <strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong> Am. J. Hum. Genet. 62: 593-598, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>] [<a href="https://doi.org/10.1086/301757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497254">Oh et al. (1998)</a> performed mutation analysis on 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication (<a href="#0001">604982.0001</a>), the result of an apparent founder effect, was nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. The mutation in these cases was a 1-bp insertion (or duplication) in a poly(C) tract at codons 322 to 324. <a href="#9" class="mim-tip-reference" title="Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A. <strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong> Am. J. Hum. Genet. 62: 593-598, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>] [<a href="https://doi.org/10.1086/301757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497254">Oh et al. (1998)</a> also described 6 novel HPS1 mutations: a 5-prime splice-junction mutation of IVS5, 3 frameshifts, a nonsense mutation, and a 1-codon in-frame deletion. These mutations defined an apparent frameshift hotspot at codons 321-322. Overall, however, they detected mutations in the HPS1 gene in only about half of non-Puerto Rican patients, and presented evidence suggesting locus heterogeneity for HPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497254" 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>The different clinical phenotypes in HPS1 associated with different frameshifts in the HPS1 gene suggested to <a href="#8" class="mim-tip-reference" title="Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A. <strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong> Nature Genet. 14: 300-306, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>] [<a href="https://doi.org/10.1038/ng1196-300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896559">Oh et al. (1996)</a> that differentially truncated HPS1 polypeptides may have somewhat different consequences for subcellular function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896559" 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>Two genetically distinct mouse loci, 'pale ear' (ep) and 'ruby-eye' (ru), both with mutant phenotypes similar to human Hermansky-Pudlak syndrome, map close together in the homologous region of murine chromosome 19, which suggested that one of these loci might be homologous to human HPS. <a href="#1" class="mim-tip-reference" title="Feng, G. H., Bailin, T., Oh, J., Spritz, R. A. <strong>Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.</strong> Hum. Molec. Genet. 6: 793-797, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158155</a>] [<a href="https://doi.org/10.1093/hmg/6.5.793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9158155">Feng et al. (1997)</a> characterized the mouse Hps cDNA and genomic locus, and identified pathologic Hps gene mutations in ep but not in ru mice, establishing mouse 'pale ear' as an animal model for human Hermansky-Pudlak syndrome. The phenotype of homozygous ep mutant mice encompasses those of both Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, suggesting that these disorders may be closely related. In addition, the mouse and human HPS genes both contain a rare 'AT-AC' intron (i.e., an intron with nonconsensus splice sites), and comparison of the sequences of this intron in the mouse and human genes identified conserved sequences that suggest a possible role for pre-mRNA secondary structure in excision of this rare class of introns. (See <a href="/entry/601428">601428</a> and <a href="/entry/601429">601429</a> for a discussion of small nuclear RNAs necessary for AT-AC intron splicing, and see <a href="#5" class="mim-tip-reference" title="Hall, S. L., Padgett, R. A. <strong>Conserved sequences in a class of rare eukaryotic nuclear introns with non-consensus splice sites.</strong> J. Molec. Biol. 239: 357-365, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8201617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8201617</a>] [<a href="https://doi.org/10.1006/jmbi.1994.1377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8201617">Hall and Padgett (1994)</a> for a discussion of introns with nonconsensus splice sites.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8201617+9158155" 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>To test for in vivo interactions between the HPS1 and HPS2 genes in the production and function of intracellular organelles, <a href="#2" class="mim-tip-reference" title="Feng, L., Novak, E. K., Hartnell, L. M., Bonifacino, J. S., Collinson, L. M., Swank, R. T. <strong>The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes.</strong> Blood 99: 1651-1658, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11861280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11861280</a>]" pmid="11861280">Feng et al. (2002)</a> created mice doubly heterozygous for the 2 mutant genes by appropriate breeding. Cooperation between the 2 genes in melanosome production was evident in increased hypopigmentation of the coat together with dramatic quantitative and qualitative alterations of melanosomes of the retinal pigment epithelium and choroid of double-mutant mice. Lysosomal and platelet dense granule abnormalities, including hyposecretion of lysosomal enzymes from kidneys and depression of serotonin concentrations of platelet dense granules were likewise more severe in double than in single mutants. Also, lysosomal enzyme concentrations were significantly increased in lungs of double-mutant mice. Interaction between the 2 genes was specific in that effects on organelles were confined to melanosomes, lysosomes, and platelet dense granules. Together, the evidence indicated that these 2 HPS genes function largely independently at the whole-organism level to affect the production and function of all 3 organelles. Furthermore, the increased lysosomal enzyme levels in lung of double-mutant mice suggested a cause of a major clinical problem of Hermansky-Pudlak syndrome, lung fibrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11861280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604982[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs281865163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865163;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/rs281865163?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=rs281865163" 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=rs281865163" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>By SSCP/heteroduplex analysis and DNA sequencing, <a href="#8" class="mim-tip-reference" title="Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A. <strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong> Nature Genet. 14: 300-306, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>] [<a href="https://doi.org/10.1038/ng1196-300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896559">Oh et al. (1996)</a> found that 22 Puerto Rican patients with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>) were homozygous for a 16-bp duplication within exon 15 of the HPS gene, resulting in a frameshift distal to codon pro496, with termination of the nonsense polypeptide at codon 586. Similarly, they found that all 11 obligate heterozygotes tested were heterozygous for the mutation. They did not observe this mutation in 5 Puerto Rican or 15 Asian controls, or in 11 non-Puerto Rican Hermansky-Pudlak syndrome patients. Although Hermansky-Pudlak syndrome is frequent on the island of Puerto Rico, it has not been reported elsewhere in the Caribbean. Apparent homogeneity of the 16-bp frameshift duplication among Puerto Rican Hermansky-Pudlak syndrome patients suggests that this mutation arose in Puerto Rico during its early population or colonization and that the frequency of the mutation was amplified as a founder effect due to occult inbreeding and genetic drift. The mutation was easily identified, even by simple agarose electrophoresis of the exon 15 PCR product, which appears abnormally large; furthermore, heterozygotes additionally exhibit a prominent aberrant heteroduplex band. Thus, diagnosis, prenatal diagnosis, and carrier testing for Hermansky-Pudlak syndrome in the Puerto Rican population, in which the expected frequency of heterozygote may be as high as 1 in 21 persons, is possible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896559" 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="Gahl, W. A., Brantly, M., Kaiser-Kupfer, M. I., Iwata, F., Hazelwood, S., Shotelersuk, V., Duffy, L. F., Kuehl, E. M., Troendle, J., Bernardini, I. <strong>Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).</strong> New Eng. J. Med. 338: 1258-1264, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9562579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9562579</a>] [<a href="https://doi.org/10.1056/NEJM199804303381803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9562579">Gahl et al. (1998)</a> stated that all identified patients with Hermansky-Pudlak syndrome in northwest Puerto Rico were found to be homozygous for the 16-bp duplication in exon 15 of the HPS gene. <a href="#4" class="mim-tip-reference" title="Gahl, W. A., Brantly, M., Kaiser-Kupfer, M. I., Iwata, F., Hazelwood, S., Shotelersuk, V., Duffy, L. F., Kuehl, E. M., Troendle, J., Bernardini, I. <strong>Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).</strong> New Eng. J. Med. 338: 1258-1264, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9562579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9562579</a>] [<a href="https://doi.org/10.1056/NEJM199804303381803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9562579">Gahl et al. (1998)</a> compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. They studied 49 patients: 27 Puerto Ricans and 22 patients from mainland United States who were not of Puerto Rican descent. The diagnosis was based on the presence of albinism and the absence of platelet dense bodies. Homozygosity for the 16-bp duplication was found in 25 of the 27 Puerto Rican patients, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80% of the predicted value. High-resolution computed tomography in all 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in 8 patients without the duplication revealed minimal fibrosis in 3 and no fibrosis in the rest. Inflammatory bowel disease developed in 8 patients (4 in each group) between 3 and 25 years of age. Thus, the 16-bp duplication in exon 15 of the HPS gene, which had been found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9562579" 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> rs281865082 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865082;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/rs281865082?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=rs281865082" 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=rs281865082" 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=RCV000005596 OR RCV000520943 OR RCV000612428 OR RCV004754245" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005596, RCV000520943, RCV000612428, RCV004754245" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005596...</a>
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<p>In a patient from the inbred Swiss kindred with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>) studied by <a href="#10" class="mim-tip-reference" title="Schallreuter, K. U., Frenk, E., Wolfe, L. S., Witkop, C. J., Wood, J. M. <strong>Hermansky-Pudlak syndrome in a Swiss population.</strong> Dermatology 187: 248-256, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8274781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8274781</a>] [<a href="https://doi.org/10.1159/000247258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8274781">Schallreuter et al. (1993)</a> and in an Irish-German HPS patient, <a href="#8" class="mim-tip-reference" title="Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A. <strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong> Nature Genet. 14: 300-306, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>] [<a href="https://doi.org/10.1038/ng1196-300" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896559">Oh et al. (1996)</a> identified homozygosity for a frameshift mutation due to an additional cytosine in a run of 8 cytosines in the HPS gene. <a href="#9" class="mim-tip-reference" title="Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A. <strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong> Am. J. Hum. Genet. 62: 593-598, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>] [<a href="https://doi.org/10.1086/301757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497254">Oh et al. (1998)</a> reported this mutation as T322insC and found that the 2 patients were divergent for intragenic polymorphisms that flank the mutation; the findings suggested that the frameshift arose independently in the 2 populations. A French patient was found to be homozygous for the frameshift mutation and for the polymorphic haplotype found in the patient of Irish-German origin, and a Scottish patient was found to be compound heterozygous for the frameshift mutation with the haplotype found in the Irish-German patient and a novel glu666-to-ter (E666X; <a href="#0003">604982.0003</a>) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8274781+9497254+8896559" 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> rs121908385 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908385;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/rs121908385?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=rs121908385" 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=rs121908385" 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=RCV000005597 OR RCV000851731" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005597, RCV000851731" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005597...</a>
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<p>In a Scottish patient with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>), <a href="#9" class="mim-tip-reference" title="Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A. <strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong> Am. J. Hum. Genet. 62: 593-598, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>] [<a href="https://doi.org/10.1086/301757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497254">Oh et al. (1998)</a> found compound heterozygosity for the T322insC frameshift mutation (<a href="#0002">604982.0002</a>) and a novel glu666-to-ter (E666X) nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497254" 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> rs281865082 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865082;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/rs281865082?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=rs281865082" 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=rs281865082" 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=RCV000005598 OR RCV001058424 OR RCV001273031 OR RCV004754246" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005598, RCV001058424, RCV001273031, RCV004754246" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005598...</a>
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<p>In a Japanese patient with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>), <a href="#9" class="mim-tip-reference" title="Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A. <strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong> Am. J. Hum. Genet. 62: 593-598, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>] [<a href="https://doi.org/10.1086/301757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497254">Oh et al. (1998)</a> identified homozygosity for a novel frameshift mutation in the HPS gene, T322delC, that involved the same poly(C) tract involved in the T322insC frameshift (<a href="#0002">604982.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497254" 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> rs121908386 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908386;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/rs121908386?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=rs121908386" 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=rs121908386" 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=RCV000005599 OR RCV005089181" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005599, RCV005089181" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005599...</a>
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<p><a href="#11" class="mim-tip-reference" title="Shotelersuk, V., Hazelwood, S., Larson, D., Iwata, F., Kaiser-Kupfer, M. I., Kuehl, E., Bernardini, I., Gahl, W. A. <strong>Three new mutations in a gene causing Hermansky-Pudlak syndrome: clinical correlations.</strong> Molec. Genet. Metab. 64: 99-107, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9705234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9705234</a>] [<a href="https://doi.org/10.1006/mgme.1998.2679" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9705234">Shotelersuk et al. (1998)</a> studied 18 non-Puerto Rican Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>) families and identified HPS mutations in 3 of them. In 1 patient, a novel glu133-to-ter (E133X) mutation was present in compound state with the previously described T322insC mutation (<a href="#0002">604982.0002</a>). The patient was a 6-year-old girl of Italian, German, and Ukrainian ancestry. Born with pale skin, she was noted to have nystagmus at 2 months of age and pale retinas at 3 months of age, when oculocutaneous albinism was diagnosed. Bruising began at 7 to 8 months of age, and Hermansky-Pudlak syndrome was diagnosed at 18 months of age based on abnormal platelet aggregation studies. Epistaxis occurred in the winter months, and prolonged bleeding accompanied a cut lip and placement of myringotomy tubes. Asthma was diagnosed at 1 year of age. There were no signs of colitis or pulmonary fibrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9705234" 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> rs281865081 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865081;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/rs281865081?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=rs281865081" 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=rs281865081" 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=RCV000005600 OR RCV000799915" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005600, RCV000799915" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005600...</a>
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<p>In a Japanese man with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>), who had oculocutaneous albinism and a bleeding diathesis, <a href="#6" class="mim-tip-reference" title="Horikawa, T., Araki, K., Fukai, K., Ueda, M., Ueda, T., Ito, S., Ichihashi, M. <strong>Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.</strong> Brit. J. Derm. 143: 635-640, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10971344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10971344</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2000.03725.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10971344">Horikawa et al. (2000)</a> identified compound heterozygous mutations in the HPS1 gene: a frameshift mutation (962_963insG) at codon 321 in exon 11, and a 5-prime splice site mutation (IVS5+5G-A; <a href="#0007">604982.0007</a>). The content of eumelanin in the patient's hairs was significantly reduced. Histologic analysis using light and electron microscopy revealed that melanocytes in the patient's epidermis contained giant melanosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10971344" 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> rs281865077 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865077;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/rs281865077?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=rs281865077" 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=rs281865077" 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=RCV000005601 OR RCV001851672 OR RCV003387717" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005601, RCV001851672, RCV003387717" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005601...</a>
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<p>For discussion of the splice site mutation in the HPS1 gene (IVS5+5G-A) that was found in compound heterozygous state in a patient with Hermansky-Pudlak syndrome (HPS1; <a href="/entry/203300">203300</a>) by <a href="#6" class="mim-tip-reference" title="Horikawa, T., Araki, K., Fukai, K., Ueda, M., Ueda, T., Ito, S., Ichihashi, M. <strong>Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.</strong> Brit. J. Derm. 143: 635-640, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10971344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10971344</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2000.03725.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10971344">Horikawa et al. (2000)</a>, see <a href="#0006">604982.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10971344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.</strong>
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Hum. Molec. Genet. 6: 793-797, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9158155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9158155</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9158155" 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/10.1093/hmg/6.5.793" target="_blank">Full Text</a>]
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Feng, L., Novak, E. K., Hartnell, L. M., Bonifacino, J. S., Collinson, L. M., Swank, R. T.
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<strong>The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes.</strong>
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Blood 99: 1651-1658, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11861280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11861280</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11861280" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Fukai1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Fukai, K., Oh, J., Frenk, E., Almodovar, C., Spritz, R. A.
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<strong>Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.</strong>
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Hum. Molec. Genet. 4: 1665-1669, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541858</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541858" 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/10.1093/hmg/4.9.1665" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Gahl1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gahl, W. A., Brantly, M., Kaiser-Kupfer, M. I., Iwata, F., Hazelwood, S., Shotelersuk, V., Duffy, L. F., Kuehl, E. M., Troendle, J., Bernardini, I.
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<strong>Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).</strong>
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New Eng. J. Med. 338: 1258-1264, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9562579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9562579</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9562579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJM199804303381803" target="_blank">Full Text</a>]
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</p>
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<a id="5" class="mim-anchor"></a>
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<a id="Hall1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hall, S. L., Padgett, R. A.
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<strong>Conserved sequences in a class of rare eukaryotic nuclear introns with non-consensus splice sites.</strong>
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J. Molec. Biol. 239: 357-365, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8201617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8201617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8201617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/jmbi.1994.1377" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Horikawa2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Horikawa, T., Araki, K., Fukai, K., Ueda, M., Ueda, T., Ito, S., Ichihashi, M.
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<strong>Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.</strong>
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Brit. J. Derm. 143: 635-640, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10971344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10971344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10971344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1365-2133.2000.03725.x" target="_blank">Full Text</a>]
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<a id="Martina2003" class="mim-anchor"></a>
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<p class="mim-text-font">
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Martina, J. A., Moriyama, K., Bonifacino, J. S.
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<strong>BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4.</strong>
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J. Biol. Chem. 278: 29376-29384, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12756248/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12756248</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12756248" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M301294200" target="_blank">Full Text</a>]
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<a id="Oh1996" class="mim-anchor"></a>
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Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A.
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<strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong>
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Nature Genet. 14: 300-306, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896559" 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/ng1196-300" target="_blank">Full Text</a>]
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<a id="Oh1998" class="mim-anchor"></a>
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Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A.
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<strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong>
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Am. J. Hum. Genet. 62: 593-598, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497254/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497254</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497254" 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/10.1086/301757" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Schallreuter1993" class="mim-anchor"></a>
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Schallreuter, K. U., Frenk, E., Wolfe, L. S., Witkop, C. J., Wood, J. M.
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<strong>Hermansky-Pudlak syndrome in a Swiss population.</strong>
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Dermatology 187: 248-256, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8274781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8274781</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8274781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000247258" target="_blank">Full Text</a>]
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Shotelersuk, V., Hazelwood, S., Larson, D., Iwata, F., Kaiser-Kupfer, M. I., Kuehl, E., Bernardini, I., Gahl, W. A.
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<strong>Three new mutations in a gene causing Hermansky-Pudlak syndrome: clinical correlations.</strong>
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Molec. Genet. Metab. 64: 99-107, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9705234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9705234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9705234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/mgme.1998.2679" target="_blank">Full Text</a>]
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Wildenberg, S. C., Fryer, J. P., Gardner, J. M., Oetting, W. S., Brilliant, M. H., King, R. A.
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<strong>Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.</strong>
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J. Invest. Derm. 110: 777-781, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9579545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9579545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9579545" 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/10.1046/j.1523-1747.1998.00183.x" target="_blank">Full Text</a>]
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<a id="Wildenberg1995" class="mim-anchor"></a>
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Wildenberg, S. C., Oetting, W. S., Almodovar, C., Krumwiede, M., White, J. G., King, R. A.
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<strong>A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2.</strong>
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Am. J. Hum. Genet. 57: 755-765, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 10/10/2003
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<span class="mim-text-font">
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Victor A. McKusick - updated : 4/23/2002<br>Victor A. McKusick - updated : 2/11/2002<br>Gary A. Bellus - updated : 4/5/2001
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Creation Date:
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<span class="mim-text-font">
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Ada Hamosh : 5/19/2000
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carol : 12/03/2020
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carol : 06/16/2020<br>carol : 09/16/2015<br>mcolton : 8/18/2015<br>carol : 11/26/2014<br>alopez : 7/1/2011<br>mgross : 11/7/2003<br>mgross : 10/10/2003<br>carol : 3/13/2003<br>carol : 3/13/2003<br>terry : 3/12/2003<br>alopez : 6/11/2002<br>ckniffin : 5/8/2002<br>alopez : 5/3/2002<br>alopez : 5/3/2002<br>terry : 4/23/2002<br>alopez : 2/11/2002<br>terry : 2/11/2002<br>carol : 1/16/2002<br>cwells : 4/13/2001<br>cwells : 4/11/2001<br>cwells : 4/5/2001<br>cwells : 4/5/2001<br>alopez : 2/27/2001<br>terry : 2/14/2001<br>alopez : 9/29/2000<br>alopez : 6/22/2000
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<strong>*</strong> 604982
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HPS1 BIOGENESIS OF LYSOSOMAL ORGANELLES COMPLEX 3, SUBUNIT 1; HPS1
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HPS1 GENE<br />
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PALE EAR, MOUSE, HOMOLOG OF
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<strong><em>HGNC Approved Gene Symbol: HPS1</em></strong>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 10q24.2
|
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:98,413,948-98,446,935 </span>
|
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</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
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</th>
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<th>
|
|
Phenotype
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</th>
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
10q24.2
|
|
</span>
|
|
</td>
|
|
|
|
|
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<td>
|
|
<span class="mim-font">
|
|
Hermansky-Pudlak syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
203300
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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|
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|
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|
<div>
|
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<br />
|
|
</div>
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|
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<div>
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|
|
|
<h4>
|
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<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
<span class="mim-text-font">
|
|
<p>Oh et al. (1996) identified the HPS1 gene by positional cloning. The HPS1 gene encodes a novel transmembrane protein that is thought to be a component of multiple cytoplasmic organelles and is apparently crucial for their normal development and function. </p><p>Wildenberg et al. (1998) demonstrated an apparent alternative transcript of the HPS1 gene. By RT-PCR and Northern blot analysis, 2 polyadenylated transcripts were found in normal human melanocytes, human bone marrow cells, human melanoma cells, lymphoblastoid cell lines, and megakaryocytic leukemia cells. Thus, the HPS1 gene is complex and may have more than 1 biologically active transcript. Wildenberg et al. (1998) noted that the same type of alternative splicing occurs in the IGHM gene (147020), resulting in membrane-bound and secreted protein products. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Martina et al. (2003) determined that HPS1 and HPS4 (606682) form a lysosomal complex that they termed BLOC3 (biogenesis of lysosome-related organelles complex-3). Coimmunoprecipitation experiments demonstrated that epitope-tagged and endogenous HPS1 and HPS4 proteins assembled with each other in vivo. The complex was predominantly cytosolic, with a small amount peripherally associated with membranes. Size exclusion chromatography and sedimentation velocity analysis of the cytosolic fraction indicated that HPS1 and HPS4 formed a moderately asymmetric complex with a molecular mass of about 175 kD. Hps4-deficient fibroblasts from light ear mice displayed normal distribution and trafficking of a lysosomal protein and an apparently normal accumulation of Zn(2+) in intracellular vesicles. In contrast, fibroblasts of AP3 (see AP3B1; 603401)-deficient pearl mice showed deficits in both of these measures. Martina et al. (2003) concluded that HPS1 and HPS4 are components of a cytosolic complex that is involved in the biogenesis of lysosomal-related organelles through a mechanism distinct from that operated by the AP3 complex. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Fukai et al. (1995) used the linkage disequilibrium mapping approach to localize the HPS1 locus in 2 groups in whom the Hermansky-Pudlak syndrome (203300) is particularly frequent: a group in Puerto Rico and a group in an isolated village in the Swiss Alps. They localized the HPS1 locus in both groups to a 0.6-cM interval in chromosome segment 10q23.1-q23.2. Wildenberg et al. (1995) likewise mapped the HPS1 locus to 10q. They collected blood samples from a relatively homogeneous population in Puerto Rico, where Hermansky-Pudlak syndrome has a frequency of about 1 in 1,800, giving a carrier frequency estimated to be 1 in 21. Analysis of pooled DNA samples allowed them to screen the genome rapidly for candidate loci and identify linkage with a marker on 10q. The result was verified with additional markers, and a maximum lod score of 5.07 at theta = 0.001 was calculated for marker D10S198. Haplotype analysis placed the HPS1 locus in a region of approximately 1 cM that contains the markers D10S198 and D10S1239. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
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</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Oh et al. (1996) identified homozygous frameshifts in the HPS1 gene in Puerto Rican, Swiss, Irish, and Japanese patients with Hermansky-Pudlak syndrome (HPS1; 203300). </p><p>Oh et al. (1998) performed mutation analysis on 44 unrelated Puerto Rican and 24 unrelated non-Puerto Rican HPS patients. A 16-bp frameshift duplication (604982.0001), the result of an apparent founder effect, was nearly ubiquitous among Puerto Rican patients. A frameshift at codon 322 may be the most frequent HPS mutation in Europeans. The mutation in these cases was a 1-bp insertion (or duplication) in a poly(C) tract at codons 322 to 324. Oh et al. (1998) also described 6 novel HPS1 mutations: a 5-prime splice-junction mutation of IVS5, 3 frameshifts, a nonsense mutation, and a 1-codon in-frame deletion. These mutations defined an apparent frameshift hotspot at codons 321-322. Overall, however, they detected mutations in the HPS1 gene in only about half of non-Puerto Rican patients, and presented evidence suggesting locus heterogeneity for HPS. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The different clinical phenotypes in HPS1 associated with different frameshifts in the HPS1 gene suggested to Oh et al. (1996) that differentially truncated HPS1 polypeptides may have somewhat different consequences for subcellular function. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Two genetically distinct mouse loci, 'pale ear' (ep) and 'ruby-eye' (ru), both with mutant phenotypes similar to human Hermansky-Pudlak syndrome, map close together in the homologous region of murine chromosome 19, which suggested that one of these loci might be homologous to human HPS. Feng et al. (1997) characterized the mouse Hps cDNA and genomic locus, and identified pathologic Hps gene mutations in ep but not in ru mice, establishing mouse 'pale ear' as an animal model for human Hermansky-Pudlak syndrome. The phenotype of homozygous ep mutant mice encompasses those of both Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, suggesting that these disorders may be closely related. In addition, the mouse and human HPS genes both contain a rare 'AT-AC' intron (i.e., an intron with nonconsensus splice sites), and comparison of the sequences of this intron in the mouse and human genes identified conserved sequences that suggest a possible role for pre-mRNA secondary structure in excision of this rare class of introns. (See 601428 and 601429 for a discussion of small nuclear RNAs necessary for AT-AC intron splicing, and see Hall and Padgett (1994) for a discussion of introns with nonconsensus splice sites.) </p><p>To test for in vivo interactions between the HPS1 and HPS2 genes in the production and function of intracellular organelles, Feng et al. (2002) created mice doubly heterozygous for the 2 mutant genes by appropriate breeding. Cooperation between the 2 genes in melanosome production was evident in increased hypopigmentation of the coat together with dramatic quantitative and qualitative alterations of melanosomes of the retinal pigment epithelium and choroid of double-mutant mice. Lysosomal and platelet dense granule abnormalities, including hyposecretion of lysosomal enzymes from kidneys and depression of serotonin concentrations of platelet dense granules were likewise more severe in double than in single mutants. Also, lysosomal enzyme concentrations were significantly increased in lungs of double-mutant mice. Interaction between the 2 genes was specific in that effects on organelles were confined to melanosomes, lysosomes, and platelet dense granules. Together, the evidence indicated that these 2 HPS genes function largely independently at the whole-organism level to affect the production and function of all 3 organelles. Furthermore, the increased lysosomal enzyme levels in lung of double-mutant mice suggested a cause of a major clinical problem of Hermansky-Pudlak syndrome, lung fibrosis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, 16-BP DUP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865163,
|
|
|
|
|
|
gnomAD: rs281865163,
|
|
|
|
|
|
ClinVar: RCV000005595, RCV000482079, RCV000614559, RCV001266458, RCV004754244
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By SSCP/heteroduplex analysis and DNA sequencing, Oh et al. (1996) found that 22 Puerto Rican patients with Hermansky-Pudlak syndrome (HPS1; 203300) were homozygous for a 16-bp duplication within exon 15 of the HPS gene, resulting in a frameshift distal to codon pro496, with termination of the nonsense polypeptide at codon 586. Similarly, they found that all 11 obligate heterozygotes tested were heterozygous for the mutation. They did not observe this mutation in 5 Puerto Rican or 15 Asian controls, or in 11 non-Puerto Rican Hermansky-Pudlak syndrome patients. Although Hermansky-Pudlak syndrome is frequent on the island of Puerto Rico, it has not been reported elsewhere in the Caribbean. Apparent homogeneity of the 16-bp frameshift duplication among Puerto Rican Hermansky-Pudlak syndrome patients suggests that this mutation arose in Puerto Rico during its early population or colonization and that the frequency of the mutation was amplified as a founder effect due to occult inbreeding and genetic drift. The mutation was easily identified, even by simple agarose electrophoresis of the exon 15 PCR product, which appears abnormally large; furthermore, heterozygotes additionally exhibit a prominent aberrant heteroduplex band. Thus, diagnosis, prenatal diagnosis, and carrier testing for Hermansky-Pudlak syndrome in the Puerto Rican population, in which the expected frequency of heterozygote may be as high as 1 in 21 persons, is possible. </p><p>Gahl et al. (1998) stated that all identified patients with Hermansky-Pudlak syndrome in northwest Puerto Rico were found to be homozygous for the 16-bp duplication in exon 15 of the HPS gene. Gahl et al. (1998) compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. They studied 49 patients: 27 Puerto Ricans and 22 patients from mainland United States who were not of Puerto Rican descent. The diagnosis was based on the presence of albinism and the absence of platelet dense bodies. Homozygosity for the 16-bp duplication was found in 25 of the 27 Puerto Rican patients, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80% of the predicted value. High-resolution computed tomography in all 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in 8 patients without the duplication revealed minimal fibrosis in 3 and no fibrosis in the rest. Inflammatory bowel disease developed in 8 patients (4 in each group) between 3 and 25 years of age. Thus, the 16-bp duplication in exon 15 of the HPS gene, which had been found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, 1-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865082,
|
|
|
|
|
|
gnomAD: rs281865082,
|
|
|
|
|
|
ClinVar: RCV000005596, RCV000520943, RCV000612428, RCV004754245
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient from the inbred Swiss kindred with Hermansky-Pudlak syndrome (HPS1; 203300) studied by Schallreuter et al. (1993) and in an Irish-German HPS patient, Oh et al. (1996) identified homozygosity for a frameshift mutation due to an additional cytosine in a run of 8 cytosines in the HPS gene. Oh et al. (1998) reported this mutation as T322insC and found that the 2 patients were divergent for intragenic polymorphisms that flank the mutation; the findings suggested that the frameshift arose independently in the 2 populations. A French patient was found to be homozygous for the frameshift mutation and for the polymorphic haplotype found in the patient of Irish-German origin, and a Scottish patient was found to be compound heterozygous for the frameshift mutation with the haplotype found in the Irish-German patient and a novel glu666-to-ter (E666X; 604982.0003) nonsense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, GLU666TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908385,
|
|
|
|
|
|
gnomAD: rs121908385,
|
|
|
|
|
|
ClinVar: RCV000005597, RCV000851731
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Scottish patient with Hermansky-Pudlak syndrome (HPS1; 203300), Oh et al. (1998) found compound heterozygosity for the T322insC frameshift mutation (604982.0002) and a novel glu666-to-ter (E666X) nonsense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, 1-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865082,
|
|
|
|
|
|
gnomAD: rs281865082,
|
|
|
|
|
|
ClinVar: RCV000005598, RCV001058424, RCV001273031, RCV004754246
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with Hermansky-Pudlak syndrome (HPS1; 203300), Oh et al. (1998) identified homozygosity for a novel frameshift mutation in the HPS gene, T322delC, that involved the same poly(C) tract involved in the T322insC frameshift (604982.0002). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, GLU133TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908386,
|
|
|
|
|
|
gnomAD: rs121908386,
|
|
|
|
|
|
ClinVar: RCV000005599, RCV005089181
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Shotelersuk et al. (1998) studied 18 non-Puerto Rican Hermansky-Pudlak syndrome (HPS1; 203300) families and identified HPS mutations in 3 of them. In 1 patient, a novel glu133-to-ter (E133X) mutation was present in compound state with the previously described T322insC mutation (604982.0002). The patient was a 6-year-old girl of Italian, German, and Ukrainian ancestry. Born with pale skin, she was noted to have nystagmus at 2 months of age and pale retinas at 3 months of age, when oculocutaneous albinism was diagnosed. Bruising began at 7 to 8 months of age, and Hermansky-Pudlak syndrome was diagnosed at 18 months of age based on abnormal platelet aggregation studies. Epistaxis occurred in the winter months, and prolonged bleeding accompanied a cut lip and placement of myringotomy tubes. Asthma was diagnosed at 1 year of age. There were no signs of colitis or pulmonary fibrosis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 HERMANSKY-PUDLAK SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HPS1, 1-BP INS, 962G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs281865081,
|
|
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gnomAD: rs281865081,
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ClinVar: RCV000005600, RCV000799915
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<p>In a Japanese man with Hermansky-Pudlak syndrome (HPS1; 203300), who had oculocutaneous albinism and a bleeding diathesis, Horikawa et al. (2000) identified compound heterozygous mutations in the HPS1 gene: a frameshift mutation (962_963insG) at codon 321 in exon 11, and a 5-prime splice site mutation (IVS5+5G-A; 604982.0007). The content of eumelanin in the patient's hairs was significantly reduced. Histologic analysis using light and electron microscopy revealed that melanocytes in the patient's epidermis contained giant melanosomes. </p>
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<span class="mim-font">
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<strong>.0007 HERMANSKY-PUDLAK SYNDROME 1</strong>
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<span class="mim-text-font">
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HPS1, IVS5DS, G-A, +5
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<br />
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SNP: rs281865077,
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gnomAD: rs281865077,
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ClinVar: RCV000005601, RCV001851672, RCV003387717
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<p>For discussion of the splice site mutation in the HPS1 gene (IVS5+5G-A) that was found in compound heterozygous state in a patient with Hermansky-Pudlak syndrome (HPS1; 203300) by Horikawa et al. (2000), see 604982.0006. </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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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Feng, G. H., Bailin, T., Oh, J., Spritz, R. A.
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<strong>Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.</strong>
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Hum. Molec. Genet. 6: 793-797, 1997.
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[PubMed: 9158155]
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[Full Text: https://doi.org/10.1093/hmg/6.5.793]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Feng, L., Novak, E. K., Hartnell, L. M., Bonifacino, J. S., Collinson, L. M., Swank, R. T.
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<strong>The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes.</strong>
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Blood 99: 1651-1658, 2002.
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[PubMed: 11861280]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fukai, K., Oh, J., Frenk, E., Almodovar, C., Spritz, R. A.
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<strong>Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.</strong>
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Hum. Molec. Genet. 4: 1665-1669, 1995.
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[PubMed: 8541858]
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[Full Text: https://doi.org/10.1093/hmg/4.9.1665]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gahl, W. A., Brantly, M., Kaiser-Kupfer, M. I., Iwata, F., Hazelwood, S., Shotelersuk, V., Duffy, L. F., Kuehl, E. M., Troendle, J., Bernardini, I.
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|
<strong>Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).</strong>
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New Eng. J. Med. 338: 1258-1264, 1998.
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[PubMed: 9562579]
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[Full Text: https://doi.org/10.1056/NEJM199804303381803]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hall, S. L., Padgett, R. A.
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<strong>Conserved sequences in a class of rare eukaryotic nuclear introns with non-consensus splice sites.</strong>
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J. Molec. Biol. 239: 357-365, 1994.
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[PubMed: 8201617]
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[Full Text: https://doi.org/10.1006/jmbi.1994.1377]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Horikawa, T., Araki, K., Fukai, K., Ueda, M., Ueda, T., Ito, S., Ichihashi, M.
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<strong>Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes.</strong>
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Brit. J. Derm. 143: 635-640, 2000.
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[PubMed: 10971344]
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[Full Text: https://doi.org/10.1111/j.1365-2133.2000.03725.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Martina, J. A., Moriyama, K., Bonifacino, J. S.
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<strong>BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4.</strong>
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J. Biol. Chem. 278: 29376-29384, 2003.
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[PubMed: 12756248]
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[Full Text: https://doi.org/10.1074/jbc.M301294200]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J., Frenk, E., Tamura, N., Spritz, R. A.
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<strong>Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.</strong>
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Nature Genet. 14: 300-306, 1996.
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[PubMed: 8896559]
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[Full Text: https://doi.org/10.1038/ng1196-300]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Oh, J., Ho, L., Ala-Mello, S., Amato, D., Armstrong, L., Bellucci, S., Carakushansky, G., Ellis, J. P., Fong, C.-T., Green, J. S., Heon, E., Legius, E., Levin, A. V., Nieuwenhuis, H. K., Pinckers, A., Tamura, N., Whiteford, M. L., Yamasaki, H., Spritz, R. A.
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|
<strong>Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity.</strong>
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Am. J. Hum. Genet. 62: 593-598, 1998.
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[PubMed: 9497254]
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[Full Text: https://doi.org/10.1086/301757]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Schallreuter, K. U., Frenk, E., Wolfe, L. S., Witkop, C. J., Wood, J. M.
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<strong>Hermansky-Pudlak syndrome in a Swiss population.</strong>
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Dermatology 187: 248-256, 1993.
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[PubMed: 8274781]
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[Full Text: https://doi.org/10.1159/000247258]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shotelersuk, V., Hazelwood, S., Larson, D., Iwata, F., Kaiser-Kupfer, M. I., Kuehl, E., Bernardini, I., Gahl, W. A.
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<strong>Three new mutations in a gene causing Hermansky-Pudlak syndrome: clinical correlations.</strong>
|
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Molec. Genet. Metab. 64: 99-107, 1998.
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[PubMed: 9705234]
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[Full Text: https://doi.org/10.1006/mgme.1998.2679]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Wildenberg, S. C., Fryer, J. P., Gardner, J. M., Oetting, W. S., Brilliant, M. H., King, R. A.
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<strong>Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.</strong>
|
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J. Invest. Derm. 110: 777-781, 1998.
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[PubMed: 9579545]
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[Full Text: https://doi.org/10.1046/j.1523-1747.1998.00183.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Wildenberg, S. C., Oetting, W. S., Almodovar, C., Krumwiede, M., White, J. G., King, R. A.
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<strong>A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2.</strong>
|
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Am. J. Hum. Genet. 57: 755-765, 1995.
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[PubMed: 7573033]
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</p>
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</li>
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</ol>
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<br />
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Patricia A. Hartz - updated : 10/10/2003<br>Victor A. McKusick - updated : 4/23/2002<br>Victor A. McKusick - updated : 2/11/2002<br>Gary A. Bellus - updated : 4/5/2001
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