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- *300535 - OCRL INOSITOL POLYPHOSPHATE-5-PHOSPHATASE; OCRL
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*300535</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/300535">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>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000122126;t=ENST00000371113" 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=4952" 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=300535" 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=ENSG00000122126;t=ENST00000371113" 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_000276,NM_001318784,NM_001587" 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_000276" 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=300535" 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=02395&isoform_id=02395_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/OCRL" 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/385337,4261633,13254464,13325070,13325072,17389991,34191133,63100298,67477390,119632235,119632236,119632237,120660444,158259675,219518136,974005362,1403730428" 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/Q01968" 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=4952" 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=ENSG00000122126;t=ENST00000371113" 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=OCRL" 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=OCRL" 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+4952" 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/OCRL" 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:4952" 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/4952" 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=chrX&hgg_gene=ENST00000371113.9&hgg_start=129540259&hgg_end=129592556&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:8108" 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:8108" 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/ocrl" 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=300535[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=300535[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/OCRL/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/ENSG00000122126" 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.gwascentral.org/search?q=OCRL" 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=OCRL" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://research.nhgri.nih.gov/lowe/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=OCRL&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/PA31896" 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:8108" 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/FBgn0023508.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:109589" 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/OCRL#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:109589" 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/4952/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=4952" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00007620;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-061110-61" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4952" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=OCRL&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 717790004, 79385002<br />
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<strong>ICD10CM:</strong> E72.03<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
|
|
300535
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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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OCRL INOSITOL POLYPHOSPHATE-5-PHOSPHATASE; OCRL
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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">
|
|
OCRL GENE<br />
|
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OCRL1
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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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=OCRL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">OCRL</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">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/X/667?start=-3&limit=10&highlight=667">Xq26.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:129540259-129592556&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'})">X:129,540,259-129,592,556</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>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=300555,309000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/667?start=-3&limit=10&highlight=667">
|
|
Xq26.1
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Dent disease 2
|
|
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<a href="/entry/300555"> 300555 </a>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Lowe syndrome
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/309000"> 309000 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
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</span>
|
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</td>
|
|
</tr>
|
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<p>The OCRL gene encodes a phosphatidylinositol 4,5-bisphosphate-5-phosphatase localized to the trans-Golgi network that is involved in actin polymerization (<a href="#22" class="mim-tip-reference" title="Suchy, S. F., Nussbaum, R. L. <strong>The deficiency of PIP(2) 5-phosphatase in Lowe syndrome affects actin polymerization.</strong> Am. J. Hum. Genet. 71: 1420-1427, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428211[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/344517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12428211">Suchy and Nussbaum, 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12428211" 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="#1" class="mim-tip-reference" title="Attree, O., Olivos, I. M., Okabe, I., Bailey, L. C., Nelson, D. L., Lewis, R. A., McInnes, R. R., Nussbaum, R. L. <strong>The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.</strong> Nature 358: 239-242, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1321346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1321346</a>] [<a href="https://doi.org/10.1038/358239a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1321346">Attree et al. (1992)</a> used YACs with inserts that span the X-chromosomal breakpoint from a female patient with Lowe oculocerebrorenal syndrome (OCRL; <a href="/entry/309000">309000</a>) as prepared by <a href="#17" class="mim-tip-reference" title="Nelson, D. L., Ballabio, A., Victoria, M. F., Pieretti, M., Bies, R. D., Gibbs, R. A., Maley, J. A., Chinault, A. C., Webster, T. D., Caskey, C. T. <strong>Alu-primed polymerase chain reaction for regional assignment of 110 yeast artificial chromosome clones from the human X chromosome: identification of clones associated with a disease locus.</strong> Proc. Nat. Acad. Sci. 88: 6157-6161, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2068096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2068096</a>] [<a href="https://doi.org/10.1073/pnas.88.14.6157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2068096">Nelson et al. (1991)</a> to screen cDNA libraries. They found that a transcript was absent in both female OCRL patients with X;autosome translocations and that it was absent or abnormal in size in 9 of 13 unrelated male OCRL patients who had no detectable genomic rearrangement. The open reading frame encodes a protein with 71% similarity to human inositol polyphosphate 5-phosphatase II (<a href="/entry/147264">147264</a>). The OCRL protein is 51% identical to inositol polyphosphate 5-phosphatase II from human platelets over a span of 744 amino acids (<a href="#24" class="mim-tip-reference" title="Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W. <strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong> Proc. Nat. Acad. Sci. 92: 4853-4856, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761412</a>] [<a href="https://doi.org/10.1073/pnas.92.11.4853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7761412">Zhang et al., 1995</a>). The results suggested that OCRL may be an inborn error of inositol phosphate metabolism. <a href="#2" class="mim-tip-reference" title="Bailey, L. C., Jr., Olivos, I. M., Leahey, A. M., Attree, O. F., Okabe, I., Lewis, R. A., MacInnes, R. R., Spinner, N. B., Nelson, D. L., Nussbaum, R. L. <strong>Characterization of a candidate gene for OCRL. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A4 only, 1992."None>Bailey et al. (1992)</a> found that the OCRL cDNA predicts a protein of 968 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7761412+1321346+2068096" 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 homology of the OCRL protein to inositol polyphosphate-5-phosphatase II suggested to <a href="#24" class="mim-tip-reference" title="Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W. <strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong> Proc. Nat. Acad. Sci. 92: 4853-4856, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761412</a>] [<a href="https://doi.org/10.1073/pnas.92.11.4853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7761412">Zhang et al. (1995)</a> that the OCRL protein may function as an isoenzyme of 5-phosphatase. <a href="#24" class="mim-tip-reference" title="Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W. <strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong> Proc. Nat. Acad. Sci. 92: 4853-4856, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761412</a>] [<a href="https://doi.org/10.1073/pnas.92.11.4853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7761412">Zhang et al. (1995)</a> engineered a construct of the OCRL cDNA that encodes amino acids homologous to the platelet 5-phosphatase for expression in baculovirus-infected Sf9 insect cells. This cDNA encoded amino acids 264 through 968 of the OCRL protein. The recombinant protein was found to catalyze the reactions also carried out by platelet 5-phosphatase II. Most important, the enzyme was found to convert phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 4-phosphate. Recombinant OCRL protein hydrolyzed phospholipid substrate 10- to 30-fold better than 5-phosphatase II, and 5-phosphatase I did not cleave the lipid at all. <a href="#24" class="mim-tip-reference" title="Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W. <strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong> Proc. Nat. Acad. Sci. 92: 4853-4856, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761412</a>] [<a href="https://doi.org/10.1073/pnas.92.11.4853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7761412">Zhang et al. (1995)</a> also showed that OCRL functions as a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in OCRL-expressing Sf9 cells. The results suggested that OCRL is mainly a lipid phosphatase that may control cellular levels of a critical metabolite, phosphatidylinositol 4,5-bisphosphate. Deficiency of this enzyme apparently causes the protean manifestations of Lowe syndrome (<a href="/entry/309000">309000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7761412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Olivos-Glander, I. M., Janne, P. A., Nussbaum, R. L. <strong>The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex.</strong> Am. J. Hum. Genet. 57: 817-823, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573041</a>]" pmid="7573041">Olivos-Glander et al. (1995)</a> used the predicted amino acid sequence of the OCRL gene to develop antibodies against the OCRL protein. Western blot analysis demonstrated a single protein of 105 kD in fibroblasts of a normal individual and absence of same in fibroblasts of an OCRL patient who lacked OCRL transcript. A single protein with the same electrophoretic mobility was found by Western analysis in various human cultured cell lines, and a protein of approximately the same size was found in all mouse tissues tested. Northern analysis of human and mouse tissues demonstrated that the mRNA is expressed in nearly all tissues examined. By immunofluorescence, the antibody stains a juxtanuclear region in normal fibroblasts, while no specific staining was evident in the OCRL patient who produced no transcript. Using a monoclonal antibody against a Golgi-specific coat protein, beta-COP (COPB; <a href="/entry/600959">600959</a>), <a href="#19" class="mim-tip-reference" title="Olivos-Glander, I. M., Janne, P. A., Nussbaum, R. L. <strong>The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex.</strong> Am. J. Hum. Genet. 57: 817-823, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573041</a>]" pmid="7573041">Olivos-Glander et al. (1995)</a> demonstrated that OCRL1 is localized to the Golgi complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573041" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In fibroblasts from patients with Lowe syndrome, <a href="#22" class="mim-tip-reference" title="Suchy, S. F., Nussbaum, R. L. <strong>The deficiency of PIP(2) 5-phosphatase in Lowe syndrome affects actin polymerization.</strong> Am. J. Hum. Genet. 71: 1420-1427, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428211[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/344517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12428211">Suchy and Nussbaum (2002)</a> identified a cellular abnormality of the actin cytoskeleton characterized by a decrease in long actin stress fibers, enhanced sensitivity to actin depolymerizing agents, and an increase in punctate F-actin staining in a distinctly anomalous distribution in the center of the cell. They also demonstrated an abnormal distribution of gelsolin (<a href="/entry/137350">137350</a>) and alpha-actinin (see <a href="/entry/102575">102575</a>), actin-binding proteins regulated by both phosphatidylinositol 4,5-bisphosphate and calcium that would be expected to be altered in Lowe cells. Actin polymerization plays a key role in the formation, maintenance, and proper function of tight junctions and adherens junctions, which are critical to renal proximal tubule function and the differentiation of the lens. The authors concluded that their findings pointed to a general mechanism to explain how this phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency might produce the Lowe syndrome phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12428211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Faucherre, A., Desbois, P., Satre, V., Lunardi, J., Dorseuil, O., Gacon, G. <strong>Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.</strong> Hum. Molec. Genet. 12: 2449-2456, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915445</a>] [<a href="https://doi.org/10.1093/hmg/ddg250" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12915445">Faucherre et al. (2003)</a> demonstrated interaction of the RhoGAP domain of OCRL1 with the Rho GTPase Rac (RAC1; <a href="/entry/602048">602048</a>). Activated Rac GTPase associated with the OCRL1 RhoGAP domain in vitro and coimmunoprecipitated with endogenous OCRL1. OCRL1 RhoGAP exhibited a significant interaction with GDP-bound Rac in vitro. Immunofluorescence studies and Golgi perturbation assays demonstrated that a fraction of endogenous Rac colocalized with OCRL1 and gamma-adaptin (<a href="/entry/603533">603533</a>) in the trans-Golgi network. The authors concluded that OCRL1 is a bifunctional protein which, in addition to its PIP2 5-phosphatase activity, binds to Rac GTPase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915445" 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="#6" class="mim-tip-reference" title="Faucherre, A., Desbois, P., Nagano, F., Satre, V., Lunardi, J., Gacon, G., Dorseuil, O. <strong>Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology.</strong> Hum. Molec. Genet. 1441-1448, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829501</a>] [<a href="https://doi.org/10.1093/hmg/ddi153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829501">Faucherre et al. (2005)</a> showed that the C-terminal RhoGAP domain of Ocrl1 formed a stable complex with activated Rac within the cell. Upon Egf (<a href="/entry/131530">131530</a>)-induced Rac activation in COS-7 cells, a fraction of Ocrl1 translocated from the trans-Golgi network to plasma membrane and was concentrated in membrane ruffles. Immunofluorescence analysis showed that PIP2 accumulated in PDGF (see <a href="/entry/173430">173430</a>)-induced ruffles in fibroblasts from patients with Lowe syndrome compared to control fibroblasts. <a href="#6" class="mim-tip-reference" title="Faucherre, A., Desbois, P., Nagano, F., Satre, V., Lunardi, J., Gacon, G., Dorseuil, O. <strong>Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology.</strong> Hum. Molec. Genet. 1441-1448, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829501</a>] [<a href="https://doi.org/10.1093/hmg/ddi153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829501">Faucherre et al. (2005)</a> suggested that Ocrl1 may be a PIP2 5-phosphatase in Rac-induced membrane ruffles, which in turn may affect cell migration and establishment of cell-cell contacts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829501" 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="Coon, B. G., Mukherjee, D., Hanna, C. B., Riese, D. J., II, Lowe, M., Aguilar, R. C. <strong>Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.</strong> Hum. Molec. Genet. 18: 4478-4491, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19700499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19700499</a>] [<a href="https://doi.org/10.1093/hmg/ddp407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19700499">Coon et al. (2009)</a> showed that OCRL1 was required for proper cell migration, spreading, and fluid-phase uptake in both established cell lines and human dermal fibroblasts. Primary fibroblasts from 2 patients with Lowe syndrome displayed defects in these cellular processes. These abnormalities were suppressed by expressing wildtype OCRL1 but not by a phosphatase-deficient mutant. The homologous human PI5-phosphatase, INPP5B (<a href="/entry/147264">147264</a>), was unable to complement the OCRL1-dependent cell migration defect. The OCRL1 variants that could not bind the endocytic adaptor AP2 (AP2A1; <a href="/entry/601026">601026</a>) or clathrin (see <a href="/entry/118955">118955</a>), like INPP5B, were less apt to rescue the migration phenotype. However, no defect in membrane recruitment of AP2/clathrin or in transferrin endocytosis by patient cells was detected. <a href="#4" class="mim-tip-reference" title="Coon, B. G., Mukherjee, D., Hanna, C. B., Riese, D. J., II, Lowe, M., Aguilar, R. C. <strong>Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.</strong> Hum. Molec. Genet. 18: 4478-4491, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19700499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19700499</a>] [<a href="https://doi.org/10.1093/hmg/ddp407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19700499">Coon et al. (2009)</a> suggested that OCRL1, but not INPP5B, may be involved in ruffle-mediated membrane remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19700499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using coimmunoprecipitation and pull-down experiments in COS-7 cells and rat brain extracts, <a href="#23" class="mim-tip-reference" title="Swan, L. E., Tomasini, L., Pirruccello, M., Lunardi, J., De Camilli, P. <strong>Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.</strong> Proc. Nat. Acad. Sci. 107: 3511-3516, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20133602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20133602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20133602[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0914658107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20133602">Swan et al. (2010)</a> found that the C termini of human FAM109A (<a href="/entry/614239">614239</a>) and FAM109B (<a href="/entry/614240">614240</a>), which they called SES1 and SES2, interacted with the ASH-RhoGAP-like domains of OCRL and INPP5B. Mutation analysis showed that SES proteins interacted with OCRL via a conserved C-terminal motif, termed the F&H motif, similar to that of another OCRL-binding protein, APPL1 (<a href="/entry/604299">604299</a>). Pull-down experiments in mouse brain extracts and transfected COS-7 cells showed that missense mutations in OPRL that disrupted binding to APPL1 in patients with Lowe syndrome or Dent disease-2 (<a href="/entry/300555">300555</a>) also abolished binding of OCRL to SES1 and SES2. In addition, APPL1 and the SES proteins could not simultaneously bind to OCRL. Immunofluorescence microscopy of transfected COS-7 cells demonstrated colocalization of human SES1 and SES2 with human OCRL in endosomes and in larger vesicles expressing EEA1 (<a href="/entry/605070">605070</a>) and WDFY2 (<a href="/entry/610418">610418</a>). Confocal microscopy suggested that APPL1 and the SES proteins associated sequentially with endosomes and that the SES proteins localized to phosphatidylinositol 3-phosphate-positive vesicles. <a href="#23" class="mim-tip-reference" title="Swan, L. E., Tomasini, L., Pirruccello, M., Lunardi, J., De Camilli, P. <strong>Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.</strong> Proc. Nat. Acad. Sci. 107: 3511-3516, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20133602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20133602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20133602[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0914658107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20133602">Swan et al. (2010)</a> proposed that Lowe syndrome and Dent disease-2 result from perturbations at multiples sites within the endocytic pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20133602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By yeast 2-hybrid analysis, pull-down assays, and native coimmunoprecipitation experiments in HeLa cells, <a href="#18" class="mim-tip-reference" title="Noakes, C. J., Lee, G., Lowe, M. <strong>The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.</strong> Molec. Biol. Cell 22: 606-623, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21233288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21233288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21233288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E10-08-0730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21233288">Noakes et al. (2011)</a> confirmed that the C termini of FAM109A and FAM109B, which they called IPIP27A and IPIP27B, bound the C-terminal ASH and RhoGAP-like domains of OCRL1 and INPP5B. Similar to the results of <a href="#23" class="mim-tip-reference" title="Swan, L. E., Tomasini, L., Pirruccello, M., Lunardi, J., De Camilli, P. <strong>Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.</strong> Proc. Nat. Acad. Sci. 107: 3511-3516, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20133602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20133602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20133602[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0914658107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20133602">Swan et al. (2010)</a>, <a href="#18" class="mim-tip-reference" title="Noakes, C. J., Lee, G., Lowe, M. <strong>The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.</strong> Molec. Biol. Cell 22: 606-623, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21233288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21233288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21233288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E10-08-0730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21233288">Noakes et al. (2011)</a> found that mutations in OCRL1 associated with Lowe syndrome abolished interaction with IPIP27A and IPIP27B. Depletion of IPIP27A and/or IPIP27B via RNA interference in HeLa cells caused enlargement of early endosomes, disrupted recycling of transferrin receptor (TFRC; <a href="/entry/190010">190010</a>), impaired the transfer of CIMPR (IGF2R; <a href="/entry/147280">147280</a>) from endosomes to the TGN, and caused missorting of lysosomal hydrolases. <a href="#18" class="mim-tip-reference" title="Noakes, C. J., Lee, G., Lowe, M. <strong>The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.</strong> Molec. Biol. Cell 22: 606-623, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21233288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21233288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21233288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1091/mbc.E10-08-0730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21233288">Noakes et al. (2011)</a> proposed that IPIP27A and IPIP27B are key players in endocytic trafficking and that defects in this process are responsible for the pathology of Lowe syndrome and Dent disease-2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20133602+21233288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Lowe Oculocerebrorenal Syndrome</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Bailey, L. C., Jr., Olivos, I. M., Leahey, A. M., Attree, O. F., Okabe, I., Lewis, R. A., MacInnes, R. R., Spinner, N. B., Nelson, D. L., Nussbaum, R. L. <strong>Characterization of a candidate gene for OCRL. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A4 only, 1992."None>Bailey et al. (1992)</a> found point mutations in the OCRL gene, including a splice mutation resulting in the deletion of 178 amino acids of 1 exon, in patients with Lowe syndrome (OCRL; <a href="/entry/309000">309000</a>).</p><p><a href="#14" class="mim-tip-reference" title="Lin, T., Orrison, B. M., Leahey, A.-M., Suchy, S. F., Bernard, D. J., Lewis, R. A., Nussbaum, R. L. <strong>Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome.</strong> Am. J. Hum. Genet. 60: 1384-1388, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199559</a>] [<a href="https://doi.org/10.1086/515471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199559">Lin et al. (1997)</a> found 11 different mutations in 12 unrelated patients with OCRL. Six were nonsense mutations and 1 was a frameshifting deletion that led to premature termination. A 1.2-kb genomic deletion of exon 14 was identified in 1. In 4 others, missense mutations or deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with phosphatidylinositol bisphosphate 5-phosphatase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I. <strong>Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.</strong> Am. J. Med. Genet. 77: 348-355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632163</a>]" pmid="9632163">Kawano et al. (1998)</a> stated that at least 13 distinct mutations had been identified in the OCRL gene. They described 1 splice site mutation and 2 missense mutations in OCRL from patients with severe or moderate phenotypes in terms of degree of mental retardation and musculoskeletal abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632163" 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>Reviewing a total of 21 mutations in 25 patients or families with Lowe syndrome, <a href="#15" class="mim-tip-reference" title="Lin, T., Orrison, B. M., Suchy, S. F., Lewis, R. A., Nussbaum, R. L. <strong>Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients.</strong> Molec. Genet. Metab. 64: 58-61, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9682219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9682219</a>] [<a href="https://doi.org/10.1006/mgme.1998.2687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9682219">Lin et al. (1998)</a> pointed out that these had occurred in only 9 of the 24 exons of the OCRL gene. Missense mutations had occurred in only exons 12 to 15 in residues highly conserved among the phosphatidylinositol 4,5-bisphosphates. These observations suggested useful strategies for mutation screening in Lowe syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9682219" 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="#21" class="mim-tip-reference" title="Satre, V., Monnier, N., Berthoin, F., Ayuso, C., Joannard, A., Jouk, P.-S., Lopez-Pajares, I., Megabarne, A., Philippe, H. J., Plauchu, H., Torres, M. L., Lunardi, J. <strong>Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.</strong> Am. J. Hum. Genet. 65: 68-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364518</a>] [<a href="https://doi.org/10.1086/302443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364518">Satre et al. (1999)</a> examined the OCRL gene in 8 unrelated patients with OCRL and found 7 new mutations and 1 recurrent in-frame deletion. Altogether, 70% of missense mutations were located in exon 15, and 52% of all mutations clustered in exons 11 to 15. They identified 2 new microsatellite markers for the OCRL locus, and observed germline mosaicism in 1 family. With the microsatellite markers, they demonstrated that the HPRT1 locus (<a href="/entry/308000">308000</a>) is located 4 cM telomeric to the OCRL locus. The French family with apparent gonadal mosaicism in the maternal grandmother consisted of a deceased affected uncle and the grandson. The grandmother appeared to transmit 3 types of the X chromosome to her offspring. <a href="#21" class="mim-tip-reference" title="Satre, V., Monnier, N., Berthoin, F., Ayuso, C., Joannard, A., Jouk, P.-S., Lopez-Pajares, I., Megabarne, A., Philippe, H. J., Plauchu, H., Torres, M. L., Lunardi, J. <strong>Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.</strong> Am. J. Hum. Genet. 65: 68-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364518</a>] [<a href="https://doi.org/10.1086/302443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10364518">Satre et al. (1999)</a> showed that it was not purely a germline mosaicism; mutation-carrying cells were found in urinary cells but not in buccal swabs or hair roots of the grandmother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By haplotyping, <a href="#16" class="mim-tip-reference" title="Monnier, N., Satre, V., Lerouge, E., Berthoin, F., Lunardi, J. <strong>OCRL1 mutation analysis in French Lowe syndrome patients: implications for molecular diagnosis strategy and genetic counseling.</strong> Hum. Mutat. 16: 157-165, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10923037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10923037</a>] [<a href="https://doi.org/10.1002/1098-1004(200008)16:2<157::AID-HUMU8>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10923037">Monnier et al. (2000)</a> identified another instance of mosaicism in a female carrier. In a total panel of 44 unrelated families affected by Lowe syndrome, they found 2 cases of germinal mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10923037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 6 unrelated patients with Lowe syndrome and their families, <a href="#20" class="mim-tip-reference" title="Roschinger, W., Muntau, A. C., Rudolph, G., Roscher, A. A., Kammerer, S. <strong>Carrier assessment in families with Lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination.</strong> Molec. Genet. Metab. 69: 213-222, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767176</a>] [<a href="https://doi.org/10.1006/mgme.1999.2955" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10767176">Roschinger et al. (2000)</a> found 6 mutations in the OCRL gene, 4 of which were novel. An ophthalmologic examination was performed in all patients and in 14 female relatives. All genotypically proven carrier females showed characteristic lenticular opacities, whereas all proven noncarriers lacked this phenotypic finding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 4.5-year-old boy with Lowe syndrome, <a href="#5" class="mim-tip-reference" title="Dumic, K. K., Anticevic, D., Petrinovic-Doresic, J., Zigman, T., Zarkovic, K., Rokic, F., Vugrek, O. <strong>Lowe syndrome--old and new evidence of secondary mitochondrial dysfunction.</strong> Europ. J. Med. Genet. 63: 104022, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712215</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32712215">Dumic et al. (2020)</a> identified a nonsense mutation in the OCRL gene (Q215X; <a href="#0010">300535.0010</a>). The mutation was identified by whole-exome sequencing. The patient's mother and sister were shown to be mutation carriers. An ophthalmologic examination in the mother was normal, but the sister had bilateral congenital cataracts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Dent Disease 2</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J. <strong>Dent disease with mutations in OCRL1.</strong> Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15627218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15627218</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15627218[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/427887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15627218">Hoopes et al. (2005)</a> reported affected members of 13 families with Dent disease-2 (DENT2; <a href="/entry/300555">300555</a>) in whom mutations in CLCN5 (<a href="/entry/300008">300008</a>) were excluded, indicating genetic heterogeneity. In 5 of these 13 families, they identified mutations in the OCRL gene (see, e.g., <a href="#0005">300535.0005</a> and <a href="#0006">300535.0006</a>). Slit-lamp examinations performed in childhood or adulthood for all 5 probands showed normal results. Unlike patients with typical Lowe syndrome, none had metabolic acidosis. Three of the 5 had mild mental retardation, whereas 2 had no developmental delay or behavioral disturbance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15627218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> identified 6 different mutations in the OCRL gene (see, e.g., <a href="#0006">300535.0006</a>-<a href="#0009">300535.0009</a>) in 8 boys from 6 of 12 families with a phenotype resembling Dent disease who did not have mutations in the CLCN5 gene. Combined with other reports, the authors stated that OCRL mutations had been found in 43 (59.7%) of 72 families with a Dent disease phenotype. All patients reported by <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> had low molecular weight proteinuria and hypercalciuria, but none had renal tubular acidosis. About half had nephrocalcinosis. Two of the 8 patients had impaired cognitive function, 1 of whom also had early ocular nuclear densities. Other more variable extrarenal features included increased lactate dehydrogenase, increased creatine kinase, short stature, and umbilical hernia, some of which were reminiscent of Lowe syndrome. <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> concluded that there is a broad phenotypic spectrum of OCRL mutations, suggesting that Dent disease-2 may be a mild variant of Lowe syndrome (<a href="#13" class="mim-tip-reference" title="Levin-Iaina, N., Dinour, D. <strong>Renal disease with OCRL1 mutations: Dent-2 or Lowe syndrome? (Editorial)</strong> J. Pediat. Genet. 1: 3-5, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625794</a>] [<a href="https://doi.org/10.3233/PGE-2012-002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625794">Levin-Iaina and Dinour, 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27625794+27625797" 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="Festa, B. P., Berquez, M., Gassama, A., Amrein, I., Ismail, H. M., Samardzija, M., Staiano, L., Luciani, A., Grimm, C., Nussbaum, R. L., De Matteis, M. A., Dorchies, O. M., Scapozza, L., Wolfer, D. P., Devuyst, O. <strong>OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease.</strong> Hum. Molec. Genet. 28: 1931-1946, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30590522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30590522</a>] [<a href="https://doi.org/10.1093/hmg/ddy449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30590522">Festa et al. (2019)</a> studied a humanized mouse model for Lowe syndrome and Dent disease-2 in which Ocrl Y/- Inpp5b -/- mice expressed human INPP5B to avoid lethality resulting from deletion of Inpp5b, an Ocrl paralog that can compensate for Ocrl loss in mice. These mice, termed Ocrl Y/- mice, were born at the expected mendelian ratio and were viable and fertile. However, they displayed growth retardation and renal Fanconi syndrome, as seen in Dent disease and Lowe syndrome. The renal Fanconi syndrome in Ocrl Y/- mice was partial, with kidney proximal tubule (PT) dysfunction characterized by albuminuria and low molecular weight (LMW) proteinuria only, with no other kidney defects. Examination of the loss of LMW proteins revealed defective receptor-mediated endocytosis caused by decreased protein level of Lrp2 (<a href="/entry/600073">600073</a>) and increased level and altered subcellular distribution of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Rearrangement of PI(4,5)P2 at lysosomal membranes altered lysosomal dynamics and function and led to accumulation of PI(4,5)P2 in endolysosomes. Lysosomal accumulation of PI(4,5)P2 resulted in aberrant F-actin polymerization, which in turn impaired Lrp2 recycling and lowered its levels in kidney PT cells. Behavioral studies showed that Ocrl Y/- mice had dysfunctional locomotricity associated with muscular defects, but no other behavioral defects seen in Lowe syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30590522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with Lowe syndrome (<a href="/entry/309000">309000</a>), Leahey et al. (<a href="#11" class="mim-tip-reference" title="Leahey, A. M., Olivos, I. M., Bailey, L. C., Nussbaum, R. L. <strong>Characterization of the molecular defects in Lowe's syndrome. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A220 only, 1992."None>1992</a>, <a href="#12" class="mim-tip-reference" title="Leahey, A.-M., Charnas, L. R., Nussbaum, R. L. <strong>Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe.</strong> Hum. Molec. Genet. 2: 461-463, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8504307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8504307</a>] [<a href="https://doi.org/10.1093/hmg/2.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8504307">1993</a>) demonstrated an 112-bp deletion (nucleotides 2686-2797) in the OCRL cDNA, resulting in a frameshift and a premature termination 9 codons downstream, where CGA (arg) was converted to UGA (ter). They used single-strand conformation polymorphism (SSCP) analysis followed by sequencing to identify the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8504307" 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">rs387906484 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906484;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906484" 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=rs387906484" 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=RCV000011604 OR RCV001588808 OR RCV002496327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011604, RCV001588808, RCV002496327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011604...</a>
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<p>In 2 unrelated patients with Lowe syndrome (<a href="/entry/309000">309000</a>), Leahey et al. (<a href="#11" class="mim-tip-reference" title="Leahey, A. M., Olivos, I. M., Bailey, L. C., Nussbaum, R. L. <strong>Characterization of the molecular defects in Lowe's syndrome. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A220 only, 1992."None>1992</a>, <a href="#12" class="mim-tip-reference" title="Leahey, A.-M., Charnas, L. R., Nussbaum, R. L. <strong>Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe.</strong> Hum. Molec. Genet. 2: 461-463, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8504307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8504307</a>] [<a href="https://doi.org/10.1093/hmg/2.4.461" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8504307">1993</a>) identified a C-to-T transition at nucleotide 2746 of their sequence resulting in a conversion of an arginine codon to a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8504307" 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">rs137853260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853260;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853260" 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=rs137853260" 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=RCV000011605 OR RCV000724256" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011605, RCV000724256" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011605...</a>
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<p>In a patient with a severe phenotype of Lowe syndrome (<a href="/entry/309000">309000</a>), <a href="#10" class="mim-tip-reference" title="Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I. <strong>Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.</strong> Am. J. Med. Genet. 77: 348-355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632163</a>]" pmid="9632163">Kawano et al. (1998)</a> described a G-to-A transition at nucleotide 1739, causing an arg577-to-gln (R577Q) amino acid substitution. The patient was a 16-year-old Japanese boy who at birth was hospitalized for 2 weeks because of failure to thrive. At age 28 days, he was treated for dehydration; bilateral cataract, proteinuria, and mild metabolic acidosis were evident. The cataracts were extracted. A family study showed punctate cataract in his mother and 2 elder sisters. The patient had proximal renal tubular acidosis, generalized amino aciduria, and hyperphosphaturia. Metabolic acidosis and rickets were treated with sodium bicarbonate and vitamin D. He had several fractures. Brain CT scan showed mild ventricular dilatation. His development was delayed, and he could not lift his head until age 16 months; his developmental quotient was estimated to be 21 at 4 years of age. He had at least 8 generalized tonic-clonic convulsions. At age 16 he could not stand, walk, eat by himself, or communicate with others. He was of short stature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632163" 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">rs137853261 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853261;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853261" 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=rs137853261" 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=RCV000011606" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011606" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011606</a>
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<p>In a patient with a moderately severe phenotype of Lowe syndrome (<a href="/entry/309000">309000</a>), <a href="#10" class="mim-tip-reference" title="Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I. <strong>Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.</strong> Am. J. Med. Genet. 77: 348-355, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632163</a>]" pmid="9632163">Kawano et al. (1998)</a> found homozygosity for a his601-to-gln (H601Q) missense mutation resulting from a C-to-G transversion at nucleotide 1812 in the OCRL gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632163" 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">rs137853262 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853262;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853262" 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=rs137853262" 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=RCV000011607" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011607" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011607</a>
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<p>In a 9-year-old boy with Dent disease (DENT2; <a href="/entry/300555">300555</a>), <a href="#9" class="mim-tip-reference" title="Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J. <strong>Dent disease with mutations in OCRL1.</strong> Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15627218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15627218</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15627218[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/427887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15627218">Hoopes et al. (2005)</a> identified a 1385A-G transition in exon 14 of the OCRL gene, resulting in a tyr462-to-cys (Y462C) amino acid change. Slit-lamp examination showed no abnormalities and metabolic acidosis was not present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15627218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 DENT DISEASE 2</strong>
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OCRL, ARG301CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853263 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853263;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853263" 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=rs137853263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011608 OR RCV000059607 OR RCV000727111 OR RCV004752699" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011608, RCV000059607, RCV000727111, RCV004752699" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011608...</a>
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<p>In their family 24 in which multiple males had Dent disease (DENT2; <a href="/entry/300555">300555</a>) that mapped to Xq25-q27.1, <a href="#9" class="mim-tip-reference" title="Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J. <strong>Dent disease with mutations in OCRL1.</strong> Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15627218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15627218</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15627218[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/427887" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15627218">Hoopes et al. (2005)</a> identified a 901C-T transition in exon 11 of the OCRL gene that resulted in an arg301-to-cys (R301C) amino acid substitution. The probands studied in the mutation analysis were 2 brothers aged 22 and 27. The pedigree contained 7 affected individuals in 4 sibships in 3 generations connected through carrier females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15627218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> identified the R301C mutation in 2 brothers with Dent disease-2. Both had low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, but no renal tubular acidosis or stones. They had normal cognition and lack of ocular abnormalities, but both had increased creatine kinase and lactate dehydrogenase. One had an umbilical hernia and the other had short stature, features reminiscent of Lowe syndrome (<a href="/entry/309000">309000</a>). The unaffected mother was a mutation carrier. <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> noted that the R301C substitution occurs in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27625797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 DENT DISEASE 2</strong>
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OCRL, ARG476TRP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853846 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853846;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853846" 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=rs137853846" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000059593" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000059593" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000059593</a>
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<span class="mim-text-font">
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<p>In 2 brothers with Dent disease-2 (DENT2; <a href="/entry/300555">300555</a>), <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> identified a 1426C-T transition in exon 15 of the OCRL gene, resulting in an arg476-to-trp (R476W) substitution in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. The unaffected mother was a mutation carrier. The patients had low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, but no renal tubular acidosis or stones. One had mild aminoaciduria. One patient had some extrarenal findings, including impaired intelligence, increased creatine kinase, short stature, and mild unilateral hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27625797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<strong>.0008 DENT DISEASE 2</strong>
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OCRL, ILE526THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124412922 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124412922;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124412922" 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=rs2124412922" 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=RCV000022864" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022864" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022864</a>
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<p>In a boy with Dent disease-2 (DENT2; <a href="/entry/300555">300555</a>), <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> identified a 1547T-C transition in exon 15 of the OCRL gene, resulting in an ile526-to-thr (I526T) substitution in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. The unaffected mother was a mutation carrier. The patient had low molecular weight proteinuria and hypercalciuria, but no renal tubular acidosis. Extrarenal findings included short stature, obesity, umbilical hernia, elevated lactate dehydrogenase, and increased creatine kinase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27625797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<strong>.0009 DENT DISEASE 2</strong>
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OCRL, 2-BP DEL, 166TT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2124388022 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2124388022;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2124388022" 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=rs2124388022" 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=RCV000022865" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022865" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022865</a>
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<p>In a boy with Dent disease-2 (DENT2; <a href="/entry/300555">300555</a>), <a href="#3" class="mim-tip-reference" title="Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M. <strong>Novel OCRL mutations in patients with Dent-2 disease.</strong> J. Pediat. Genet. 1: 15-23, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>] [<a href="https://doi.org/10.3233/PGE-2012-005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27625797">Bockenhauer et al. (2012)</a> identified a 2-bp deletion (166delTT) in exon 4 of the OCRL gene, resulting in a frameshift. The patient had low molecular weight proteinuria, hypercalciuria, and mild aminoaciduria, but no other extrarenal abnormalities. His unaffected mother carried the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27625797" 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>.0010 LOWE OCULOCEREBRORENAL SYNDROME</strong>
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OCRL, GLN215TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1936103770 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1936103770;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1936103770" 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=rs1936103770" 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=RCV001172281" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001172281" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001172281</a>
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<p>In a boy with Lowe oculocerebrorenal syndrome (OCRL; <a href="/entry/309000">309000</a>), <a href="#5" class="mim-tip-reference" title="Dumic, K. K., Anticevic, D., Petrinovic-Doresic, J., Zigman, T., Zarkovic, K., Rokic, F., Vugrek, O. <strong>Lowe syndrome--old and new evidence of secondary mitochondrial dysfunction.</strong> Europ. J. Med. Genet. 63: 104022, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712215</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32712215">Dumic et al. (2020)</a> identified a c.643C-T transition (c.643C-T, NM_000276.4) in exon 10 of the OCRL gene, resulting in a gln215-to-ter (Q215X) substitution. The mutation was found by whole-exome sequencing. The patient's mother and sister were shown to be mutation carriers. The mutation was not present in the 1000 Genomes Project, ExAC, gnomAD, or dbSNP databases. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Attree1992" class="mim-anchor"></a>
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<div class="">
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Attree, O., Olivos, I. M., Okabe, I., Bailey, L. C., Nelson, D. L., Lewis, R. A., McInnes, R. R., Nussbaum, R. L.
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<strong>The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.</strong>
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Nature 358: 239-242, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1321346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1321346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1321346" 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/10.1038/358239a0" target="_blank">Full Text</a>]
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<a id="Bailey1992" class="mim-anchor"></a>
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Bailey, L. C., Jr., Olivos, I. M., Leahey, A. M., Attree, O. F., Okabe, I., Lewis, R. A., MacInnes, R. R., Spinner, N. B., Nelson, D. L., Nussbaum, R. L.
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<strong>Characterization of a candidate gene for OCRL. (Abstract)</strong>
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Am. J. Hum. Genet. 51 (suppl.): A4 only, 1992.
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<a id="Bockenhauer2012" class="mim-anchor"></a>
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Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M.
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<strong>Novel OCRL mutations in patients with Dent-2 disease.</strong>
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J. Pediat. Genet. 1: 15-23, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27625797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27625797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27625797" 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/10.3233/PGE-2012-005" target="_blank">Full Text</a>]
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<a id="Coon2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Coon, B. G., Mukherjee, D., Hanna, C. B., Riese, D. J., II, Lowe, M., Aguilar, R. C.
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<strong>Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.</strong>
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Hum. Molec. Genet. 18: 4478-4491, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19700499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19700499</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19700499" 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/ddp407" target="_blank">Full Text</a>]
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<a id="Dumic2020" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Dumic, K. K., Anticevic, D., Petrinovic-Doresic, J., Zigman, T., Zarkovic, K., Rokic, F., Vugrek, O.
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<strong>Lowe syndrome--old and new evidence of secondary mitochondrial dysfunction.</strong>
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Europ. J. Med. Genet. 63: 104022, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32712215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32712215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32712215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.104022" target="_blank">Full Text</a>]
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<a id="Faucherre2005" class="mim-anchor"></a>
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<p class="mim-text-font">
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Faucherre, A., Desbois, P., Nagano, F., Satre, V., Lunardi, J., Gacon, G., Dorseuil, O.
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<strong>Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology.</strong>
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Hum. Molec. Genet. 1441-1448, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829501</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829501" 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/ddi153" target="_blank">Full Text</a>]
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<a id="Faucherre2003" class="mim-anchor"></a>
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<div class="">
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Faucherre, A., Desbois, P., Satre, V., Lunardi, J., Dorseuil, O., Gacon, G.
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<strong>Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.</strong>
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Hum. Molec. Genet. 12: 2449-2456, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12915445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12915445</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12915445" 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/ddg250" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Festa2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Festa, B. P., Berquez, M., Gassama, A., Amrein, I., Ismail, H. M., Samardzija, M., Staiano, L., Luciani, A., Grimm, C., Nussbaum, R. L., De Matteis, M. A., Dorchies, O. M., Scapozza, L., Wolfer, D. P., Devuyst, O.
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<strong>OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease.</strong>
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Hum. Molec. Genet. 28: 1931-1946, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30590522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30590522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30590522" 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/ddy449" target="_blank">Full Text</a>]
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<a id="Hoopes2005" class="mim-anchor"></a>
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Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J.
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<strong>Dent disease with mutations in OCRL1.</strong>
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Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15627218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15627218</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15627218[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15627218" 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/10.1086/427887" target="_blank">Full Text</a>]
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<a id="Kawano1998" class="mim-anchor"></a>
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<div class="">
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Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I.
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<strong>Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.</strong>
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Am. J. Med. Genet. 77: 348-355, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9632163/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9632163</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9632163" 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="Leahey1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Leahey, A. M., Olivos, I. M., Bailey, L. C., Nussbaum, R. L.
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<strong>Characterization of the molecular defects in Lowe's syndrome. (Abstract)</strong>
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Am. J. Hum. Genet. 51 (suppl.): A220 only, 1992.
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<a id="Leahey1993" class="mim-anchor"></a>
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<div class="">
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Leahey, A.-M., Charnas, L. R., Nussbaum, R. L.
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<strong>Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe.</strong>
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Hum. Molec. Genet. 2: 461-463, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8504307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8504307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8504307" 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/2.4.461" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.3233/PGE-2012-002" target="_blank">Full Text</a>]
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<a id="Lin1997" class="mim-anchor"></a>
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<strong>Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome.</strong>
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[<a href="https://doi.org/10.1086/515471" target="_blank">Full Text</a>]
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Lin, T., Orrison, B. M., Suchy, S. F., Lewis, R. A., Nussbaum, R. L.
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<strong>Mutations are not uniformly distributed throughout the OCRL1 gene in Lowe syndrome patients.</strong>
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Molec. Genet. Metab. 64: 58-61, 1998.
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[<a href="https://doi.org/10.1006/mgme.1998.2687" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/1098-1004(200008)16:2<157::AID-HUMU8>3.0.CO;2-9" target="_blank">Full Text</a>]
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Nelson, D. L., Ballabio, A., Victoria, M. F., Pieretti, M., Bies, R. D., Gibbs, R. A., Maley, J. A., Chinault, A. C., Webster, T. D., Caskey, C. T.
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[<a href="https://doi.org/10.1073/pnas.88.14.6157" target="_blank">Full Text</a>]
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<strong>The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21233288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21233288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21233288[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21233288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1091/mbc.E10-08-0730" target="_blank">Full Text</a>]
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Olivos-Glander, I. M., Janne, P. A., Nussbaum, R. L.
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<strong>The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex.</strong>
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Am. J. Hum. Genet. 57: 817-823, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7573041/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7573041</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7573041" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Roschinger, W., Muntau, A. C., Rudolph, G., Roscher, A. A., Kammerer, S.
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<strong>Carrier assessment in families with Lowe oculocerebrorenal syndrome: novel mutations in the OCRL1 gene and correlation of direct DNA diagnosis with ocular examination.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767176" 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.1999.2955" target="_blank">Full Text</a>]
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Satre, V., Monnier, N., Berthoin, F., Ayuso, C., Joannard, A., Jouk, P.-S., Lopez-Pajares, I., Megabarne, A., Philippe, H. J., Plauchu, H., Torres, M. L., Lunardi, J.
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<strong>Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.</strong>
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Am. J. Hum. Genet. 65: 68-76, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10364518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10364518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10364518" 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/10.1086/302443" target="_blank">Full Text</a>]
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Suchy, S. F., Nussbaum, R. L.
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<strong>The deficiency of PIP(2) 5-phosphatase in Lowe syndrome affects actin polymerization.</strong>
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Am. J. Hum. Genet. 71: 1420-1427, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12428211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12428211</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12428211[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12428211" 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/10.1086/344517" target="_blank">Full Text</a>]
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<strong>Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20133602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20133602</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20133602[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20133602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0914658107" target="_blank">Full Text</a>]
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Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W.
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<strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong>
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Proc. Nat. Acad. Sci. 92: 4853-4856, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761412</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7761412" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 06/22/2021
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Bao Lige - updated : 03/09/2020<br>Cassandra L. Kniffin - updated : 4/24/2012<br>Paul J. Converse - updated : 9/21/2011<br>George E. Tiller - updated : 10/26/2010<br>George E. Tiller - updated : 6/5/2008<br>George E. Tiller - updated : 10/20/2005<br>Anne M. Stumpf - updated : 4/19/2005
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carol : 06/22/2021<br>mgross : 03/09/2020<br>carol : 02/28/2020<br>carol : 06/26/2015<br>carol : 12/19/2013<br>terry : 4/30/2012<br>carol : 4/30/2012<br>ckniffin : 4/24/2012<br>mgross : 9/21/2011<br>wwang : 11/8/2010<br>terry : 10/26/2010<br>joanna : 10/9/2008<br>wwang : 6/10/2008<br>terry : 6/5/2008<br>carol : 8/15/2007<br>alopez : 10/20/2005<br>carol : 9/19/2005<br>ckniffin : 9/7/2005<br>alopez : 4/25/2005<br>alopez : 4/19/2005<br>alopez : 4/18/2005<br>alopez : 4/18/2005
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OCRL INOSITOL POLYPHOSPHATE-5-PHOSPHATASE; OCRL
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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OCRL GENE<br />
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OCRL1
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: OCRL</em></strong>
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<strong>SNOMEDCT:</strong> 717790004, 79385002;
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<strong>ICD10CM:</strong> E72.03;
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<strong>
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<em>
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Cytogenetic location: Xq26.1
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Genomic coordinates <span class="small">(GRCh38)</span> : X:129,540,259-129,592,556 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<tbody>
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<span class="mim-font">
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Xq26.1
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Dent disease 2
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300555
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X-linked recessive
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<span class="mim-font">
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3
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Lowe syndrome
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309000
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X-linked recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>The OCRL gene encodes a phosphatidylinositol 4,5-bisphosphate-5-phosphatase localized to the trans-Golgi network that is involved in actin polymerization (Suchy and Nussbaum, 2002). </p>
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<strong>Cloning and Expression</strong>
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<p>Attree et al. (1992) used YACs with inserts that span the X-chromosomal breakpoint from a female patient with Lowe oculocerebrorenal syndrome (OCRL; 309000) as prepared by Nelson et al. (1991) to screen cDNA libraries. They found that a transcript was absent in both female OCRL patients with X;autosome translocations and that it was absent or abnormal in size in 9 of 13 unrelated male OCRL patients who had no detectable genomic rearrangement. The open reading frame encodes a protein with 71% similarity to human inositol polyphosphate 5-phosphatase II (147264). The OCRL protein is 51% identical to inositol polyphosphate 5-phosphatase II from human platelets over a span of 744 amino acids (Zhang et al., 1995). The results suggested that OCRL may be an inborn error of inositol phosphate metabolism. Bailey et al. (1992) found that the OCRL cDNA predicts a protein of 968 amino acids. </p>
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<strong>Gene Function</strong>
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<p>The homology of the OCRL protein to inositol polyphosphate-5-phosphatase II suggested to Zhang et al. (1995) that the OCRL protein may function as an isoenzyme of 5-phosphatase. Zhang et al. (1995) engineered a construct of the OCRL cDNA that encodes amino acids homologous to the platelet 5-phosphatase for expression in baculovirus-infected Sf9 insect cells. This cDNA encoded amino acids 264 through 968 of the OCRL protein. The recombinant protein was found to catalyze the reactions also carried out by platelet 5-phosphatase II. Most important, the enzyme was found to convert phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 4-phosphate. Recombinant OCRL protein hydrolyzed phospholipid substrate 10- to 30-fold better than 5-phosphatase II, and 5-phosphatase I did not cleave the lipid at all. Zhang et al. (1995) also showed that OCRL functions as a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in OCRL-expressing Sf9 cells. The results suggested that OCRL is mainly a lipid phosphatase that may control cellular levels of a critical metabolite, phosphatidylinositol 4,5-bisphosphate. Deficiency of this enzyme apparently causes the protean manifestations of Lowe syndrome (309000). </p><p>Olivos-Glander et al. (1995) used the predicted amino acid sequence of the OCRL gene to develop antibodies against the OCRL protein. Western blot analysis demonstrated a single protein of 105 kD in fibroblasts of a normal individual and absence of same in fibroblasts of an OCRL patient who lacked OCRL transcript. A single protein with the same electrophoretic mobility was found by Western analysis in various human cultured cell lines, and a protein of approximately the same size was found in all mouse tissues tested. Northern analysis of human and mouse tissues demonstrated that the mRNA is expressed in nearly all tissues examined. By immunofluorescence, the antibody stains a juxtanuclear region in normal fibroblasts, while no specific staining was evident in the OCRL patient who produced no transcript. Using a monoclonal antibody against a Golgi-specific coat protein, beta-COP (COPB; 600959), Olivos-Glander et al. (1995) demonstrated that OCRL1 is localized to the Golgi complex. </p><p>In fibroblasts from patients with Lowe syndrome, Suchy and Nussbaum (2002) identified a cellular abnormality of the actin cytoskeleton characterized by a decrease in long actin stress fibers, enhanced sensitivity to actin depolymerizing agents, and an increase in punctate F-actin staining in a distinctly anomalous distribution in the center of the cell. They also demonstrated an abnormal distribution of gelsolin (137350) and alpha-actinin (see 102575), actin-binding proteins regulated by both phosphatidylinositol 4,5-bisphosphate and calcium that would be expected to be altered in Lowe cells. Actin polymerization plays a key role in the formation, maintenance, and proper function of tight junctions and adherens junctions, which are critical to renal proximal tubule function and the differentiation of the lens. The authors concluded that their findings pointed to a general mechanism to explain how this phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency might produce the Lowe syndrome phenotype. </p><p>Faucherre et al. (2003) demonstrated interaction of the RhoGAP domain of OCRL1 with the Rho GTPase Rac (RAC1; 602048). Activated Rac GTPase associated with the OCRL1 RhoGAP domain in vitro and coimmunoprecipitated with endogenous OCRL1. OCRL1 RhoGAP exhibited a significant interaction with GDP-bound Rac in vitro. Immunofluorescence studies and Golgi perturbation assays demonstrated that a fraction of endogenous Rac colocalized with OCRL1 and gamma-adaptin (603533) in the trans-Golgi network. The authors concluded that OCRL1 is a bifunctional protein which, in addition to its PIP2 5-phosphatase activity, binds to Rac GTPase. </p><p>Faucherre et al. (2005) showed that the C-terminal RhoGAP domain of Ocrl1 formed a stable complex with activated Rac within the cell. Upon Egf (131530)-induced Rac activation in COS-7 cells, a fraction of Ocrl1 translocated from the trans-Golgi network to plasma membrane and was concentrated in membrane ruffles. Immunofluorescence analysis showed that PIP2 accumulated in PDGF (see 173430)-induced ruffles in fibroblasts from patients with Lowe syndrome compared to control fibroblasts. Faucherre et al. (2005) suggested that Ocrl1 may be a PIP2 5-phosphatase in Rac-induced membrane ruffles, which in turn may affect cell migration and establishment of cell-cell contacts. </p><p>Coon et al. (2009) showed that OCRL1 was required for proper cell migration, spreading, and fluid-phase uptake in both established cell lines and human dermal fibroblasts. Primary fibroblasts from 2 patients with Lowe syndrome displayed defects in these cellular processes. These abnormalities were suppressed by expressing wildtype OCRL1 but not by a phosphatase-deficient mutant. The homologous human PI5-phosphatase, INPP5B (147264), was unable to complement the OCRL1-dependent cell migration defect. The OCRL1 variants that could not bind the endocytic adaptor AP2 (AP2A1; 601026) or clathrin (see 118955), like INPP5B, were less apt to rescue the migration phenotype. However, no defect in membrane recruitment of AP2/clathrin or in transferrin endocytosis by patient cells was detected. Coon et al. (2009) suggested that OCRL1, but not INPP5B, may be involved in ruffle-mediated membrane remodeling. </p><p>Using coimmunoprecipitation and pull-down experiments in COS-7 cells and rat brain extracts, Swan et al. (2010) found that the C termini of human FAM109A (614239) and FAM109B (614240), which they called SES1 and SES2, interacted with the ASH-RhoGAP-like domains of OCRL and INPP5B. Mutation analysis showed that SES proteins interacted with OCRL via a conserved C-terminal motif, termed the F&H motif, similar to that of another OCRL-binding protein, APPL1 (604299). Pull-down experiments in mouse brain extracts and transfected COS-7 cells showed that missense mutations in OPRL that disrupted binding to APPL1 in patients with Lowe syndrome or Dent disease-2 (300555) also abolished binding of OCRL to SES1 and SES2. In addition, APPL1 and the SES proteins could not simultaneously bind to OCRL. Immunofluorescence microscopy of transfected COS-7 cells demonstrated colocalization of human SES1 and SES2 with human OCRL in endosomes and in larger vesicles expressing EEA1 (605070) and WDFY2 (610418). Confocal microscopy suggested that APPL1 and the SES proteins associated sequentially with endosomes and that the SES proteins localized to phosphatidylinositol 3-phosphate-positive vesicles. Swan et al. (2010) proposed that Lowe syndrome and Dent disease-2 result from perturbations at multiples sites within the endocytic pathway. </p><p>By yeast 2-hybrid analysis, pull-down assays, and native coimmunoprecipitation experiments in HeLa cells, Noakes et al. (2011) confirmed that the C termini of FAM109A and FAM109B, which they called IPIP27A and IPIP27B, bound the C-terminal ASH and RhoGAP-like domains of OCRL1 and INPP5B. Similar to the results of Swan et al. (2010), Noakes et al. (2011) found that mutations in OCRL1 associated with Lowe syndrome abolished interaction with IPIP27A and IPIP27B. Depletion of IPIP27A and/or IPIP27B via RNA interference in HeLa cells caused enlargement of early endosomes, disrupted recycling of transferrin receptor (TFRC; 190010), impaired the transfer of CIMPR (IGF2R; 147280) from endosomes to the TGN, and caused missorting of lysosomal hydrolases. Noakes et al. (2011) proposed that IPIP27A and IPIP27B are key players in endocytic trafficking and that defects in this process are responsible for the pathology of Lowe syndrome and Dent disease-2. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p><strong><em>Lowe Oculocerebrorenal Syndrome</em></strong></p><p>
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Bailey et al. (1992) found point mutations in the OCRL gene, including a splice mutation resulting in the deletion of 178 amino acids of 1 exon, in patients with Lowe syndrome (OCRL; 309000).</p><p>Lin et al. (1997) found 11 different mutations in 12 unrelated patients with OCRL. Six were nonsense mutations and 1 was a frameshifting deletion that led to premature termination. A 1.2-kb genomic deletion of exon 14 was identified in 1. In 4 others, missense mutations or deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with phosphatidylinositol bisphosphate 5-phosphatase activity. </p><p>Kawano et al. (1998) stated that at least 13 distinct mutations had been identified in the OCRL gene. They described 1 splice site mutation and 2 missense mutations in OCRL from patients with severe or moderate phenotypes in terms of degree of mental retardation and musculoskeletal abnormalities. </p><p>Reviewing a total of 21 mutations in 25 patients or families with Lowe syndrome, Lin et al. (1998) pointed out that these had occurred in only 9 of the 24 exons of the OCRL gene. Missense mutations had occurred in only exons 12 to 15 in residues highly conserved among the phosphatidylinositol 4,5-bisphosphates. These observations suggested useful strategies for mutation screening in Lowe syndrome. </p><p>Satre et al. (1999) examined the OCRL gene in 8 unrelated patients with OCRL and found 7 new mutations and 1 recurrent in-frame deletion. Altogether, 70% of missense mutations were located in exon 15, and 52% of all mutations clustered in exons 11 to 15. They identified 2 new microsatellite markers for the OCRL locus, and observed germline mosaicism in 1 family. With the microsatellite markers, they demonstrated that the HPRT1 locus (308000) is located 4 cM telomeric to the OCRL locus. The French family with apparent gonadal mosaicism in the maternal grandmother consisted of a deceased affected uncle and the grandson. The grandmother appeared to transmit 3 types of the X chromosome to her offspring. Satre et al. (1999) showed that it was not purely a germline mosaicism; mutation-carrying cells were found in urinary cells but not in buccal swabs or hair roots of the grandmother. </p><p>By haplotyping, Monnier et al. (2000) identified another instance of mosaicism in a female carrier. In a total panel of 44 unrelated families affected by Lowe syndrome, they found 2 cases of germinal mosaicism. </p><p>In a study of 6 unrelated patients with Lowe syndrome and their families, Roschinger et al. (2000) found 6 mutations in the OCRL gene, 4 of which were novel. An ophthalmologic examination was performed in all patients and in 14 female relatives. All genotypically proven carrier females showed characteristic lenticular opacities, whereas all proven noncarriers lacked this phenotypic finding. </p><p>In a 4.5-year-old boy with Lowe syndrome, Dumic et al. (2020) identified a nonsense mutation in the OCRL gene (Q215X; 300535.0010). The mutation was identified by whole-exome sequencing. The patient's mother and sister were shown to be mutation carriers. An ophthalmologic examination in the mother was normal, but the sister had bilateral congenital cataracts. </p><p><strong><em>Dent Disease 2</em></strong></p><p>
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Hoopes et al. (2005) reported affected members of 13 families with Dent disease-2 (DENT2; 300555) in whom mutations in CLCN5 (300008) were excluded, indicating genetic heterogeneity. In 5 of these 13 families, they identified mutations in the OCRL gene (see, e.g., 300535.0005 and 300535.0006). Slit-lamp examinations performed in childhood or adulthood for all 5 probands showed normal results. Unlike patients with typical Lowe syndrome, none had metabolic acidosis. Three of the 5 had mild mental retardation, whereas 2 had no developmental delay or behavioral disturbance. </p><p>Bockenhauer et al. (2012) identified 6 different mutations in the OCRL gene (see, e.g., 300535.0006-300535.0009) in 8 boys from 6 of 12 families with a phenotype resembling Dent disease who did not have mutations in the CLCN5 gene. Combined with other reports, the authors stated that OCRL mutations had been found in 43 (59.7%) of 72 families with a Dent disease phenotype. All patients reported by Bockenhauer et al. (2012) had low molecular weight proteinuria and hypercalciuria, but none had renal tubular acidosis. About half had nephrocalcinosis. Two of the 8 patients had impaired cognitive function, 1 of whom also had early ocular nuclear densities. Other more variable extrarenal features included increased lactate dehydrogenase, increased creatine kinase, short stature, and umbilical hernia, some of which were reminiscent of Lowe syndrome. Bockenhauer et al. (2012) concluded that there is a broad phenotypic spectrum of OCRL mutations, suggesting that Dent disease-2 may be a mild variant of Lowe syndrome (Levin-Iaina and Dinour, 2012). </p>
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<span class="mim-font">
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<strong>Animal Model</strong>
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<p>Festa et al. (2019) studied a humanized mouse model for Lowe syndrome and Dent disease-2 in which Ocrl Y/- Inpp5b -/- mice expressed human INPP5B to avoid lethality resulting from deletion of Inpp5b, an Ocrl paralog that can compensate for Ocrl loss in mice. These mice, termed Ocrl Y/- mice, were born at the expected mendelian ratio and were viable and fertile. However, they displayed growth retardation and renal Fanconi syndrome, as seen in Dent disease and Lowe syndrome. The renal Fanconi syndrome in Ocrl Y/- mice was partial, with kidney proximal tubule (PT) dysfunction characterized by albuminuria and low molecular weight (LMW) proteinuria only, with no other kidney defects. Examination of the loss of LMW proteins revealed defective receptor-mediated endocytosis caused by decreased protein level of Lrp2 (600073) and increased level and altered subcellular distribution of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Rearrangement of PI(4,5)P2 at lysosomal membranes altered lysosomal dynamics and function and led to accumulation of PI(4,5)P2 in endolysosomes. Lysosomal accumulation of PI(4,5)P2 resulted in aberrant F-actin polymerization, which in turn impaired Lrp2 recycling and lowered its levels in kidney PT cells. Behavioral studies showed that Ocrl Y/- mice had dysfunctional locomotricity associated with muscular defects, but no other behavioral defects seen in Lowe syndrome. </p>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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<strong>10 Selected Examples):</strong>
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<h4>
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<span class="mim-font">
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<strong>.0001 LOWE OCULOCEREBRORENAL SYNDROME</strong>
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OCRL, 112-BP DEL
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<br />
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SNP: rs2124430398,
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ClinVar: RCV000011603
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<span class="mim-text-font">
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<p>In a patient with Lowe syndrome (309000), Leahey et al. (1992, 1993) demonstrated an 112-bp deletion (nucleotides 2686-2797) in the OCRL cDNA, resulting in a frameshift and a premature termination 9 codons downstream, where CGA (arg) was converted to UGA (ter). They used single-strand conformation polymorphism (SSCP) analysis followed by sequencing to identify the mutation. </p>
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<span class="mim-font">
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<strong>.0002 LOWE OCULOCEREBRORENAL SYNDROME</strong>
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<span class="mim-text-font">
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OCRL, ARG-TER
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<br />
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SNP: rs387906484,
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ClinVar: RCV000011604, RCV001588808, RCV002496327
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<span class="mim-text-font">
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<p>In 2 unrelated patients with Lowe syndrome (309000), Leahey et al. (1992, 1993) identified a C-to-T transition at nucleotide 2746 of their sequence resulting in a conversion of an arginine codon to a stop codon. </p>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 LOWE OCULOCEREBRORENAL SYNDROME</strong>
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</span>
|
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</h4>
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</div>
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<div>
|
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<span class="mim-text-font">
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OCRL, ARG577GLN
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<br />
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SNP: rs137853260,
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ClinVar: RCV000011605, RCV000724256
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with a severe phenotype of Lowe syndrome (309000), Kawano et al. (1998) described a G-to-A transition at nucleotide 1739, causing an arg577-to-gln (R577Q) amino acid substitution. The patient was a 16-year-old Japanese boy who at birth was hospitalized for 2 weeks because of failure to thrive. At age 28 days, he was treated for dehydration; bilateral cataract, proteinuria, and mild metabolic acidosis were evident. The cataracts were extracted. A family study showed punctate cataract in his mother and 2 elder sisters. The patient had proximal renal tubular acidosis, generalized amino aciduria, and hyperphosphaturia. Metabolic acidosis and rickets were treated with sodium bicarbonate and vitamin D. He had several fractures. Brain CT scan showed mild ventricular dilatation. His development was delayed, and he could not lift his head until age 16 months; his developmental quotient was estimated to be 21 at 4 years of age. He had at least 8 generalized tonic-clonic convulsions. At age 16 he could not stand, walk, eat by himself, or communicate with others. He was of short stature. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0004 LOWE OCULOCEREBRORENAL SYNDROME</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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OCRL, HIS601GLN
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<br />
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SNP: rs137853261,
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ClinVar: RCV000011606
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with a moderately severe phenotype of Lowe syndrome (309000), Kawano et al. (1998) found homozygosity for a his601-to-gln (H601Q) missense mutation resulting from a C-to-G transversion at nucleotide 1812 in the OCRL gene. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
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|
<span class="mim-font">
|
|
<strong>.0005 DENT DISEASE 2</strong>
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|
</span>
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|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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OCRL, TYR462CYS
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<br />
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SNP: rs137853262,
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ClinVar: RCV000011607
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy with Dent disease (DENT2; 300555), Hoopes et al. (2005) identified a 1385A-G transition in exon 14 of the OCRL gene, resulting in a tyr462-to-cys (Y462C) amino acid change. Slit-lamp examination showed no abnormalities and metabolic acidosis was not present. </p>
|
|
</span>
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|
</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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<div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DENT DISEASE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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OCRL, ARG301CYS
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<br />
|
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|
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SNP: rs137853263,
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ClinVar: RCV000011608, RCV000059607, RCV000727111, RCV004752699
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|
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</span>
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|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In their family 24 in which multiple males had Dent disease (DENT2; 300555) that mapped to Xq25-q27.1, Hoopes et al. (2005) identified a 901C-T transition in exon 11 of the OCRL gene that resulted in an arg301-to-cys (R301C) amino acid substitution. The probands studied in the mutation analysis were 2 brothers aged 22 and 27. The pedigree contained 7 affected individuals in 4 sibships in 3 generations connected through carrier females. </p><p>Bockenhauer et al. (2012) identified the R301C mutation in 2 brothers with Dent disease-2. Both had low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, but no renal tubular acidosis or stones. They had normal cognition and lack of ocular abnormalities, but both had increased creatine kinase and lactate dehydrogenase. One had an umbilical hernia and the other had short stature, features reminiscent of Lowe syndrome (309000). The unaffected mother was a mutation carrier. Bockenhauer et al. (2012) noted that the R301C substitution occurs in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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|
|
</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DENT DISEASE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
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|
|
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OCRL, ARG476TRP
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|
<br />
|
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|
|
SNP: rs137853846,
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|
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|
|
|
ClinVar: RCV000059593
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with Dent disease-2 (DENT2; 300555), Bockenhauer et al. (2012) identified a 1426C-T transition in exon 15 of the OCRL gene, resulting in an arg476-to-trp (R476W) substitution in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. The unaffected mother was a mutation carrier. The patients had low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, but no renal tubular acidosis or stones. One had mild aminoaciduria. One patient had some extrarenal findings, including impaired intelligence, increased creatine kinase, short stature, and mild unilateral hearing loss. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DENT DISEASE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OCRL, ILE526THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124412922,
|
|
|
|
|
|
|
|
ClinVar: RCV000022864
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with Dent disease-2 (DENT2; 300555), Bockenhauer et al. (2012) identified a 1547T-C transition in exon 15 of the OCRL gene, resulting in an ile526-to-thr (I526T) substitution in a highly conserved residue in the exonuclease-endonuclease-phosphatase domain. The unaffected mother was a mutation carrier. The patient had low molecular weight proteinuria and hypercalciuria, but no renal tubular acidosis. Extrarenal findings included short stature, obesity, umbilical hernia, elevated lactate dehydrogenase, and increased creatine kinase. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DENT DISEASE 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OCRL, 2-BP DEL, 166TT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2124388022,
|
|
|
|
|
|
|
|
ClinVar: RCV000022865
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with Dent disease-2 (DENT2; 300555), Bockenhauer et al. (2012) identified a 2-bp deletion (166delTT) in exon 4 of the OCRL gene, resulting in a frameshift. The patient had low molecular weight proteinuria, hypercalciuria, and mild aminoaciduria, but no other extrarenal abnormalities. His unaffected mother carried the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 LOWE OCULOCEREBRORENAL SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
OCRL, GLN215TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1936103770,
|
|
|
|
|
|
|
|
ClinVar: RCV001172281
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with Lowe oculocerebrorenal syndrome (OCRL; 309000), Dumic et al. (2020) identified a c.643C-T transition (c.643C-T, NM_000276.4) in exon 10 of the OCRL gene, resulting in a gln215-to-ter (Q215X) substitution. The mutation was found by whole-exome sequencing. The patient's mother and sister were shown to be mutation carriers. The mutation was not present in the 1000 Genomes Project, ExAC, gnomAD, or dbSNP databases. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
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|
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|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Attree, O., Olivos, I. M., Okabe, I., Bailey, L. C., Nelson, D. L., Lewis, R. A., McInnes, R. R., Nussbaum, R. L.
|
|
<strong>The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.</strong>
|
|
Nature 358: 239-242, 1992.
|
|
|
|
|
|
[PubMed: 1321346]
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|
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|
|
[Full Text: https://doi.org/10.1038/358239a0]
|
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bailey, L. C., Jr., Olivos, I. M., Leahey, A. M., Attree, O. F., Okabe, I., Lewis, R. A., MacInnes, R. R., Spinner, N. B., Nelson, D. L., Nussbaum, R. L.
|
|
<strong>Characterization of a candidate gene for OCRL. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A4 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bockenhauer, D., Bokenkamp, A., Nuutinen, M., Unwin, R., van't Hoff, W., Sirimanna, T., Vrljicak, K., Ludwig, M.
|
|
<strong>Novel OCRL mutations in patients with Dent-2 disease.</strong>
|
|
J. Pediat. Genet. 1: 15-23, 2012.
|
|
|
|
|
|
[PubMed: 27625797]
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|
|
[Full Text: https://doi.org/10.3233/PGE-2012-005]
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</p>
|
|
</li>
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|
<li>
|
|
<p class="mim-text-font">
|
|
Coon, B. G., Mukherjee, D., Hanna, C. B., Riese, D. J., II, Lowe, M., Aguilar, R. C.
|
|
<strong>Lowe syndrome patient fibroblasts display Ocrl1-specific cell migration defects that cannot be rescued by the homologous Inpp5b phosphatase.</strong>
|
|
Hum. Molec. Genet. 18: 4478-4491, 2009.
|
|
|
|
|
|
[PubMed: 19700499]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddp407]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dumic, K. K., Anticevic, D., Petrinovic-Doresic, J., Zigman, T., Zarkovic, K., Rokic, F., Vugrek, O.
|
|
<strong>Lowe syndrome--old and new evidence of secondary mitochondrial dysfunction.</strong>
|
|
Europ. J. Med. Genet. 63: 104022, 2020.
|
|
|
|
|
|
[PubMed: 32712215]
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|
[Full Text: https://doi.org/10.1016/j.ejmg.2020.104022]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faucherre, A., Desbois, P., Nagano, F., Satre, V., Lunardi, J., Gacon, G., Dorseuil, O.
|
|
<strong>Lowe syndrome protein Ocrl1 is translocated to membrane ruffles upon Rac GTPase activation: a new perspective on Lowe syndrome pathophysiology.</strong>
|
|
Hum. Molec. Genet. 1441-1448, 2005.
|
|
|
|
|
|
[PubMed: 15829501]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddi153]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faucherre, A., Desbois, P., Satre, V., Lunardi, J., Dorseuil, O., Gacon, G.
|
|
<strong>Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network.</strong>
|
|
Hum. Molec. Genet. 12: 2449-2456, 2003.
|
|
|
|
|
|
[PubMed: 12915445]
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|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg250]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Festa, B. P., Berquez, M., Gassama, A., Amrein, I., Ismail, H. M., Samardzija, M., Staiano, L., Luciani, A., Grimm, C., Nussbaum, R. L., De Matteis, M. A., Dorchies, O. M., Scapozza, L., Wolfer, D. P., Devuyst, O.
|
|
<strong>OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease.</strong>
|
|
Hum. Molec. Genet. 28: 1931-1946, 2019.
|
|
|
|
|
|
[PubMed: 30590522]
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|
|
[Full Text: https://doi.org/10.1093/hmg/ddy449]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoopes, R. R., Shrimpton, A. E., Knohl, S. J., Hueber, P., Hoppe, B., Matyus, J., Simckes, A., Tasic, V., Toenshoff, B., Suchy, S. F., Nussbaum, R. L., Scheinman, S. J.
|
|
<strong>Dent disease with mutations in OCRL1.</strong>
|
|
Am. J. Hum. Genet. 76: 260-267, 2005. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.
|
|
|
|
|
|
[PubMed: 15627218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/427887]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawano, T., Indo, Y., Nakazato, H., Shimadzu, M., Matsuda, I.
|
|
<strong>Oculocerebrorenal syndrome of Lowe: three mutations in the OCRL1 gene derived from three patients with different phenotypes.</strong>
|
|
Am. J. Med. Genet. 77: 348-355, 1998.
|
|
|
|
|
|
[PubMed: 9632163]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leahey, A. M., Olivos, I. M., Bailey, L. C., Nussbaum, R. L.
|
|
<strong>Characterization of the molecular defects in Lowe's syndrome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A220 only, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leahey, A.-M., Charnas, L. R., Nussbaum, R. L.
|
|
<strong>Nonsense mutations in the OCRL-1 gene in patients with the oculocerebrorenal syndrome of Lowe.</strong>
|
|
Hum. Molec. Genet. 2: 461-463, 1993.
|
|
|
|
|
|
[PubMed: 8504307]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/2.4.461]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Levin-Iaina, N., Dinour, D.
|
|
<strong>Renal disease with OCRL1 mutations: Dent-2 or Lowe syndrome? (Editorial)</strong>
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<strong>The oculocerebrorenal syndrome gene product is a 105-kD protein localized to the Golgi complex.</strong>
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Suchy, S. F., Nussbaum, R. L.
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<strong>The deficiency of PIP(2) 5-phosphatase in Lowe syndrome affects actin polymerization.</strong>
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Zhang, X., Jefferson, A. B., Auethavekiat, V., Majerus, P. W.
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<strong>The protein deficient in Lowe syndrome is a phosphatidylinositol-4,5-bisphosphate 5-phosphatase.</strong>
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