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Entry
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- *107777 - AQUAPORIN 2; AQP2
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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">*107777</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/107777">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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</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 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=ENSG00000167580;t=ENST00000199280" 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=359" 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=107777" 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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<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=ENSG00000167580;t=ENST00000199280" 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_000486" 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_000486" 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=107777" 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=00141&isoform_id=00141_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/AQP2" 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/474059,567250,684999,685001,728874,4262709,4502179,5052748,21103957,27769002,49457001,119578513" 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/P41181" 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=359" 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=ENSG00000167580;t=ENST00000199280" 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=AQP2" 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=AQP2" 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+359" 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/AQP2" 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:359" 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/359" 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=chr12&hgg_gene=ENST00000199280.4&hgg_start=49950737&hgg_end=49958878&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://medlineplus.gov/genetics/gene/aqp2" 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=107777[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=107777[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/AQP2/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/ENSG00000167580" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=AQP2" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=AQP2" 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=AQP2" 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://www.medicine.mcgill.ca/nephros/" 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=AQP2&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/PA24920" 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:634" 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/FBgn0015872.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:1096865" 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/AQP2#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:1096865" 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/359/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=359" 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>
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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:359" 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=AQP2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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107777
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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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AQUAPORIN 2; AQP2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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AQUAPORIN-CD
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=AQP2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AQP2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/12/365?start=-3&limit=10&highlight=365">12q13.12</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:49950737-49958878&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'})">12:49,950,737-49,958,878</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/12/365?start=-3&limit=10&highlight=365">
|
|
12q13.12
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Diabetes insipidus, nephrogenic, 2
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<a href="/entry/125800"> 125800 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/107777" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/107777" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The AQP2 gene encodes an aquaporin-2 water channel located in the renal collecting tubules. Aquaporin-CHIP (AQP1; <a href="/entry/107776">107776</a>) is located in the proximal renal tubule (<a href="#8" class="mim-tip-reference" title="Fushimi, K., Uchida, S., Hara, Y., Hirata, Y., Marumo, F., Sasaki, S. <strong>Cloning and expression of apical membrane water channel of rat kidney collecting tubule.</strong> Nature 361: 549-552, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429910</a>] [<a href="https://doi.org/10.1038/361549a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8429910">Fushimi et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8429910" 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="Fushimi, K., Uchida, S., Hara, Y., Hirata, Y., Marumo, F., Sasaki, S. <strong>Cloning and expression of apical membrane water channel of rat kidney collecting tubule.</strong> Nature 361: 549-552, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429910</a>] [<a href="https://doi.org/10.1038/361549a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8429910">Fushimi et al. (1993)</a> cloned the cDNA for the water channel of the apical membrane of the kidney collecting tubule in the rat. The gene shows 42% identity in amino acid sequence to AQP1. Expression in Xenopus oocytes markedly increased osmotic water permeability (Pf). The functional expression and the limited localization suggested that AQP2 is the vasopressin-regulated water channel. <a href="#8" class="mim-tip-reference" title="Fushimi, K., Uchida, S., Hara, Y., Hirata, Y., Marumo, F., Sasaki, S. <strong>Cloning and expression of apical membrane water channel of rat kidney collecting tubule.</strong> Nature 361: 549-552, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8429910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8429910</a>] [<a href="https://doi.org/10.1038/361549a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8429910">Fushimi et al. (1993)</a> referred to AQP2 as WCH-CD, for 'water channel-collecting duct.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8429910" 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>Sasaki et al. (<a href="#23" class="mim-tip-reference" title="Sasaki, S., Saito, H., Saito, F., Fushimi, K., Uchida, S., Rai, Y., Ikeuchi, T., Inui, K., Marumo, F. <strong>Cloning, expression and chromosomal mapping of human collecting duct water channel (hWCH-CD). (Abstract)</strong> J. Am. Soc. Nephrol. 4: 858 only, 1993."None>1993</a>, <a href="#22" class="mim-tip-reference" title="Sasaki, S., Fushimi, K., Saito, H., Saito, F., Uchida, S., Ishibashi, K., Kuwahara, M., Ikeuchi, T., Inui, K., Nakajima, K., Watanabe, T. X., Marumo, F. <strong>Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.</strong> J. Clin. Invest. 93: 1250-1256, 1994. Note: Erratum: J. Clin. Invest. 94: following 216, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7510718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7510718</a>] [<a href="https://doi.org/10.1172/JCI117079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7510718">1994</a>) cloned a cDNA for human AQP2 and found that it encodes a deduced protein with 91% amino acid identity to the rat protein. By screening kidney cDNA in cosmid libraries with a rat AQP2 cDNA probe, <a href="#7" class="mim-tip-reference" title="Deen, P. M. T., Weghuis, D. O., Sinke, R. J., Geurts van Kessel, A., Wieringa, B., van Os, C. H. <strong>Assignment of the human gene for the water channel of renal collecting duct aquaporin 2 (AQP2) to chromosome 12 region q12-q13.</strong> Cytogenet. Cell Genet. 66: 260-262, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7512890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7512890</a>] [<a href="https://doi.org/10.1159/000133707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7512890">Deen et al. (1994)</a> isolated human AQP2. They found that the predicted amino acid sequence shares 89.7% identity with the rat protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7510718+7512890" 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="#18" class="mim-tip-reference" title="Nielsen, S., Chou, C.-L., Marples, D., Christensen, E. I., Kishore, B. K., Knepper, M. A. <strong>Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.</strong> Proc. Nat. Acad. Sci. 92: 1013-1017, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7532304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7532304</a>] [<a href="https://doi.org/10.1073/pnas.92.4.1013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7532304">Nielsen et al. (1995)</a> showed that arginine vasopressin (AVP; <a href="/entry/192340">192340</a>) increases cellular water permeability by inducing exocytosis of AQP2-laden vesicles, transferring water channels from intracellular vesicles to the apical plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7532304" 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 rat kidney slices and porcine kidney cells stably expressing rat Aqp2, <a href="#1" class="mim-tip-reference" title="Bouley, R., Breton, S., Sun, T., McLaughlin, M., Nsumu, N. N., Lin, H. Y., Ausiello, D. A., Brown, D. <strong>Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells.</strong> J. Clin. Invest. 106: 1115-1126, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11067864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11067864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11067864[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/10.1172/JCI9594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11067864">Bouley et al. (2000)</a> demonstrated that AQP2 trafficking can be stimulated by cAMP-independent pathways that utilize nitric oxide (NO). The NO donors sodium nitroprusside (SNP) and NONOate and the NO synthase (see <a href="/entry/163731">163731</a>) substrate L-arginine mimicked the effect of vasopressin (VP), stimulating relocation of Aqp2 from cytoplasmic vesicles to the apical plasma membrane. SNP increased intracellular cGMP rather than cAMP, and exogenous cGMP stimulated AQP2 membrane insertion. Atrial natriuretic factor (<a href="/entry/108780">108780</a>), which signals via cGMP, also stimulated AQP2 translocation. Both the VP and SNP effects were blocked by a kinase inhibitor, and membrane insertion was blocked in cells expressing the phosphorylation-deficient mutant ser256 to ala, indicating that ser256 is required for signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11067864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Kanno, K., Sasaki, S., Hirata, Y., Ishikawa, S., Fushimi, K., Nakanishi, S., Bichet, D. G., Marumo, F. <strong>Urinary excretion of aquaporin-2 in patients with diabetes insipidus.</strong> New Eng. J. Med. 332: 1540-1545, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7537863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7537863</a>] [<a href="https://doi.org/10.1056/NEJM199506083322303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7537863">Kanno et al. (1995)</a> reported that aquaporin-2 is detectable in the urine in both soluble and membrane-bound forms. In normal subjects, an infusion of desmopressin increased the urinary excretion of aquaporin-2. In 5 patients with central diabetes insipidus (CDI; <a href="/entry/125700">125700</a>), administration of desmopressin increased urinary excretion of aquaporin-2; however, this response was not seen in 4 patients with X-linked (NDI1; <a href="/entry/304800">304800</a>) or autosomal recessive nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>). <a href="#21" class="mim-tip-reference" title="Saito, T., Ishikawa, S.-E., Sasaki, S., Nakamura, T., Rokkaku, K., Kawakami, A., Honda, K., Marumo, F., Saito, T. <strong>Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.</strong> J. Clin. Endocr. Metab. 82: 1823-1827, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9177390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9177390</a>] [<a href="https://doi.org/10.1210/jcem.82.6.3984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9177390">Saito et al. (1997)</a> determined that measuring urinary excretion of AQP2 is of value in diagnosing central diabetes insipidus. In normal subjects under ad libitum water drinking, urinary AQP2 was positively correlated with plasma arginine vasopressin levels, but not with urinary osmolality. <a href="#21" class="mim-tip-reference" title="Saito, T., Ishikawa, S.-E., Sasaki, S., Nakamura, T., Rokkaku, K., Kawakami, A., Honda, K., Marumo, F., Saito, T. <strong>Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.</strong> J. Clin. Endocr. Metab. 82: 1823-1827, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9177390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9177390</a>] [<a href="https://doi.org/10.1210/jcem.82.6.3984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9177390">Saito et al. (1997)</a> found that measurement of AQP2 was also helpful when using a hypertonic saline infusion to diagnose CDI. <a href="#20" class="mim-tip-reference" title="Saito, T., Ishikawa, S.-E., Ito, T., Oda, H., Ando, F., Higashiyama, M., Nagasaka, S., Hieda, M., Saito, T. <strong>Urinary excretion of aquaporin-2 water channel differentiates psychogenic polydipsia from central diabetes insipidus.</strong> J. Clin. Endocr. Metab. 84: 2235-2237, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10372737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10372737</a>] [<a href="https://doi.org/10.1210/jcem.84.6.5715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10372737">Saito et al. (1999)</a> investigated whether urinary excretion of AQP2 under ad libitum water intake was of value in the differentiation between psychogenic polydipsia and CDI. A 30-minute urine collection was made at 0900 hours in 3 groups: 11 patients with CDI (22 to 68 years old), 10 patients with psychogenic polydipsia (28 to 60 years old), and 15 normal subjects (21 to 38 years old). In the patients with CDI, the plasma arginine vasopressin level was low despite hyperosmolality, resulting in hypotonic urine. Urinary excretion of AQP2 was 37 +/- 15 fmol/mg creatinine, a value one-fifth less than that in the normal subjects. In the patients with psychogenic polydipsia, plasma arginine vasopressin and urinary osmolality were as low as those in the patients with CDI. However, urinary excretion of AQP2 of 187 +/- 45 fmol/mg creatinine was not decreased, and its excretion was equal to that in the normal subjects. The results indicated that urinary excretion of AQP2, under ad libitum water drinking, participates in the differentiation of psychogenic polydipsia from CDI. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7537863+9177390+10372737" 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="Ishikawa, S., Saito, T., Fukagawa, A., Higashiyama, M., Nakamura, T., Kusaka, I., Nagasaka, S., Honda, K., Saito, T. <strong>Close association of urinary excretion of aquaporin-2 with appropriate and inappropriate arginine vasopressin-dependent antidiuresis in hyponatremia in elderly subjects.</strong> J. Clin. Endocr. Metab. 86: 1665-1671, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11297601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11297601</a>] [<a href="https://doi.org/10.1210/jcem.86.4.7426" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11297601">Ishikawa et al. (2001)</a> undertook to determine whether urinary excretion of AQP2 participates in the involvement of arginine vasopressin in hyponatremia less than 130 mmol/L in 33 elderly subjects more than 64 years of age during the last 5-year period. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP2 and antidiuresis. Plasma AVP and urinary excretion of AQP2 were not reduced after an acute water load test. The inappropriate secretion of AVP was evident in the patients with the syndrome of inappropriate secretion of diuretic hormone (SIADH) and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP2 and renal water excretion in those with hypopituitarism. The authors concluded that urinary excretion of AQP2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11297601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in situ hybridization, Sasaki et al. (<a href="#23" class="mim-tip-reference" title="Sasaki, S., Saito, H., Saito, F., Fushimi, K., Uchida, S., Rai, Y., Ikeuchi, T., Inui, K., Marumo, F. <strong>Cloning, expression and chromosomal mapping of human collecting duct water channel (hWCH-CD). (Abstract)</strong> J. Am. Soc. Nephrol. 4: 858 only, 1993."None>1993</a>, <a href="#22" class="mim-tip-reference" title="Sasaki, S., Fushimi, K., Saito, H., Saito, F., Uchida, S., Ishibashi, K., Kuwahara, M., Ikeuchi, T., Inui, K., Nakajima, K., Watanabe, T. X., Marumo, F. <strong>Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.</strong> J. Clin. Invest. 93: 1250-1256, 1994. Note: Erratum: J. Clin. Invest. 94: following 216, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7510718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7510718</a>] [<a href="https://doi.org/10.1172/JCI117079" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7510718">1994</a>) mapped the AQP2 gene to chromosome 12q13, very close to the site of major intrinsic protein (MIP; <a href="/entry/154050">154050</a>). The investigators suggested that a defect in the AQP2 gene is the basis of the autosomal form of nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7510718" 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="Deen, P. M. T., Weghuis, D. O., Sinke, R. J., Geurts van Kessel, A., Wieringa, B., van Os, C. H. <strong>Assignment of the human gene for the water channel of renal collecting duct aquaporin 2 (AQP2) to chromosome 12 region q12-q13.</strong> Cytogenet. Cell Genet. 66: 260-262, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7512890/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7512890</a>] [<a href="https://doi.org/10.1159/000133707" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7512890">Deen et al. (1994)</a> used fluorescence in situ hybridization to map the AQP2 gene to chromosome 12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7512890" 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 male patient with autosomal recessive nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#6" class="mim-tip-reference" title="Deen, P. M. T., Verdijk, M. A. J., Knoers, N. V. A. M., Wieringa, B., Monnens, L. A. H., van Os, C. H., van Oost, B. A. <strong>Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.</strong> Science 264: 92-94, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8140421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8140421</a>] [<a href="https://doi.org/10.1126/science.8140421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8140421">Deen et al. (1994)</a> identified compound heterozygosity for 2 mutations in the AQP2 gene (R187C, <a href="#0001">107777.0001</a> and S216P, <a href="#0002">107777.0002</a>). Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. <a href="#5" class="mim-tip-reference" title="Deen, P. M. T., Croes, H., van Aubel, R. A. M. H., Ginsel, L. A., van Os, C. H. <strong>Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing.</strong> J. Clin. Invest. 95: 2291-2296, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7537761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7537761</a>] [<a href="https://doi.org/10.1172/JCI117920" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7537761">Deen et al. (1995)</a> found that expression of 3 mutant AQP2 proteins, R187C, S216P, and G64R (<a href="#0004">107777.0004</a>), in Xenopus oocytes resulted in nonfunctional water channels. The transcripts encoding the missense AQPs were translated as efficiently as wildtype transcript and were equally stable. Immunocytochemistry demonstrated that the mutant AQP2 did not label in the plasma membrane. The authors proposed that the inability of the AQP2 proteins to facilitate water transport was caused by an impaired routing to the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8140421+7537761" 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>Missense mutations and a single-nucleotide deletion in the AQP2 gene were found by <a href="#24" class="mim-tip-reference" title="van Lieburg, A. F., Verdijk, M. A. J., Knoers, V. V. A. M., van Essen, A. J., Proesmans, W., Mallmann, R., Monnens, L. A. H., van Oost, B. A., van Os, C. H., Deen, P. M. T. <strong>Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.</strong> Am. J. Hum. Genet. 55: 648-652, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7524315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7524315</a>]" pmid="7524315">van Lieburg et al. (1994)</a> in 3 NDI patients from consanguineous families (<a href="#0001">107777.0001</a>; <a href="#0004">107777.0004</a>-<a href="#0005">107777.0005</a>). Expression studies in Xenopus oocytes showed that the mutated AQP2 proteins were nonfunctional. <a href="#17" class="mim-tip-reference" title="Mulders, S. M., Knoers, N. V. A. M., van Lieburg, A. F., Monnens, L. A. H., Leumann, E., Wuhl, E., Schober, E., Rijss, J. P. L., van Os, C. H., Deen, P. M. T. <strong>New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.</strong> J. Am. Soc. Nephrol. 8: 242-248, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048343</a>] [<a href="https://doi.org/10.1681/ASN.V82242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9048343">Mulders et al. (1997)</a> reported 3 additional NDI patients who were homozygous for mutations in the AQP2 gene. Functional expression studies showed that 2 of the mutations (<a href="#0006">107777.0006</a> and <a href="#0007">107777.0007</a>) resulted in functional proteins that were apparently retained in the endoplasmic reticulum and impaired in their routing to the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9048343+7524315" 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 a Dutch family with autosomal dominant NDI, <a href="#16" class="mim-tip-reference" title="Mulders, S. M., Bichet, D. G., Rijss, J. P. L., Kamsteeg, E.-J., Arthus, M.-F., Lonergan, M., Fujiwara, M., Morgan, K., Leijendekker, R., van der Sluijs, P., van Os, C. H., Deen, P. M. T. <strong>An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.</strong> J. Clin. Invest. 102: 57-66, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9649557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9649557</a>] [<a href="https://doi.org/10.1172/JCI2605" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9649557">Mulders et al. (1998)</a> identified a mutation (<a href="#0009">107777.0009</a>) in the AQP2 gene that exhibited a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9649557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 3 unrelated families with autosomal dominant NDI, <a href="#12" class="mim-tip-reference" title="Kuwahara, M., Iwai, K., Ooeda, T., Igarashi, T., Ogawa, E., Katsushima, Y., Shinbo, I., Uchida, S., Terada, Y., Arthus, M.-F., Lonergan, M., Fujiwara, T. M., Bichet, D. G., Marumo, F., Sasaki, S. <strong>Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.</strong> Am. J. Hum. Genet. 69: 738-748, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11536078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11536078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11536078[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/10.1086/323643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11536078">Kuwahara et al. (2001)</a> identified 3 different deletion mutations in exon 4 of the AQP2 gene (see, e.g., <a href="#0014">107777.0014</a>), all of which resulted in an elongated protein with a C-terminal tail of 61 amino acids. The predicted wildtype AQP2 protein contains 271 amino acids, whereas the predicted mutant proteins contained 330 to 333 amino acids because of the frameshift. In Xenopus oocytes injected with mutant AQP2 cRNAs, the osmotic water permeability was much smaller than that of oocytes with the AQP2 wildtype (14 to 17%). The results suggested that the trafficking of mutant AQP2 was impaired due to elongation of the C-terminal tail. The dominant-negative effect was attributed to oligomerization of the wildtype and mutant AQP2s. <a href="#14" class="mim-tip-reference" title="Marr, N., Bichet, D. G., Lonergan, M., Arthus, M.-F., Jeck, N., Seyberth, H. W., Rosenthal, W., van Os, C. H., Oksche, A., Deen, P. M. T. <strong>Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.</strong> Hum. Molec. Genet. 11: 779-789, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929850</a>] [<a href="https://doi.org/10.1093/hmg/11.7.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11929850">Marr et al. (2002)</a> reported similar findings (see <a href="#0015">107777.0015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11536078+11929850" 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="Carroll, P., Al-Mojalli, H., Al-Abbad, A., Al-Hassoun, I., Al-Hamed, M., Al-Amr, R., Butt, A. I., Meyer, B. F. <strong>Novel mutations underlying nephrogenic diabetes insipidus in Arab families.</strong> Genet. Med. 8: 443-447, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16845277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16845277</a>] [<a href="https://doi.org/10.1097/01.gim.0000223554.46981.7a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16845277">Carroll et al. (2006)</a> identified the molecular basis of NDI in Arab families. Two novel missense mutations were identified in AQP2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16845277" 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="#25" class="mim-tip-reference" title="Yang, B., Gillespie, A., Carlson, E. J., Epstein, C. J., Verkman, A. S. <strong>Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus.</strong> J. Biol. Chem. 276: 2775-2779, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11035038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11035038</a>] [<a href="https://doi.org/10.1074/jbc.M008216200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11035038">Yang et al. (2001)</a> generated a mouse knockin model of NDI generated by targeted gene replacement with the thr126-to-met mutation (T126M; <a href="#0007">107777.0007</a>) along with mutations to preserve the consensus sequence for N-linked glycosylation found in human AQP2. The mutant mice died within 6 days after birth unless given supplemental fluid. Urine/serum analysis showed a urinary concentrating defect with serum hyperosmolality and low urine osmolality that could not be corrected by a V2 vasopressin agonist. Northern blot analysis revealed upregulated Aqp2-T126M transcripts identical in size to wildtype Aqp2. Immunoblot analysis indicated complex glycosylation of wildtype Aqp2 but endoglycosidase H-sensitive core glycosylation of the mutant, suggesting ER retention. Immunohistologic and histologic analyses revealed kidney collecting duct dilatation, papillary atrophy, and some plasma membrane Aqp2 expression. <a href="#25" class="mim-tip-reference" title="Yang, B., Gillespie, A., Carlson, E. J., Epstein, C. J., Verkman, A. S. <strong>Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus.</strong> J. Biol. Chem. 276: 2775-2779, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11035038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11035038</a>] [<a href="https://doi.org/10.1074/jbc.M008216200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11035038">Yang et al. (2001)</a> concluded that the Aqp2-T126M mutant creates a more severe phenotype than those observed in mice lacking water channels Aqp1, Aqp3 (<a href="/entry/600170">600170</a>), or Aqp4 (<a href="/entry/600308">600308</a>), and establishes a mouse model of human autosomal NDI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11035038" 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="Rojek, A., Fuchtbauer, E.-M., Kwon, T.-H., Frokiaer, J., Nielsen, S. <strong>Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice.</strong> Proc. Nat. Acad. Sci. 103: 6037-6042, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16581908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16581908</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16581908[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.0511324103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16581908">Rojek et al. (2006)</a> found that Aqp2-null mice appeared normal at birth but failed to thrive and died within 2 weeks of age. Kidneys from Aqp2-null pups showed papillary atrophy and signs of hydronephrosis. Mice with Aqp2 knockout targeted to the renal collecting ducts survived to adulthood, but they showed decreased body weight, 10-fold increased urine production, and decreased urinary osmolality and were unable to adapt to water deprivation. <a href="#19" class="mim-tip-reference" title="Rojek, A., Fuchtbauer, E.-M., Kwon, T.-H., Frokiaer, J., Nielsen, S. <strong>Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice.</strong> Proc. Nat. Acad. Sci. 103: 6037-6042, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16581908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16581908</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16581908[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.0511324103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16581908">Rojek et al. (2006)</a> concluded that AQP2 expression in kidney connecting tubules is sufficient for survival and that AQP2 expression in collecting ducts is required to regulate body water balance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16581908" 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>Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation that causes severe hydronephrosis and obstructive nephropathy in mice. <a href="#15" class="mim-tip-reference" title="McDill, B. W., Li, S.-Z., Kovach, P. A., Ding, L., Chen, F. <strong>Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation.</strong> Proc. Nat. Acad. Sci. 103: 6952-6957, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16641094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16641094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16641094[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.0602087103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16641094">McDill et al. (2006)</a> found that homozygous cph mice were born at mendelian ratios and appeared grossly normal at birth, but they grew slowly and showed significant size and weight differences from postnatal day 8 onward. About 90% of cph mice died between 2 and 4 weeks of age. By 2 weeks, most had visibly enlarged abdomens and appeared lethargic. <a href="#15" class="mim-tip-reference" title="McDill, B. W., Li, S.-Z., Kovach, P. A., Ding, L., Chen, F. <strong>Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation.</strong> Proc. Nat. Acad. Sci. 103: 6952-6957, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16641094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16641094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16641094[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.0602087103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16641094">McDill et al. (2006)</a> identified a ser256-to-leu (S256L) mutation in the Aqp2 gene as the cause of cph. The S256L substitution in the cytoplasmic tail of the Aqp2 protein prevented phosphorylation at S256 and the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct principal cells. The interference with normal trafficking of Aqp2 by the S256L mutation resulted in a severe urine concentration defect. The NDI symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery before the onset of hydronephrosis suggested that the congenital obstructive nephropathy was likely the result of the polyuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16641094" 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>.0001 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894328 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894328;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894328?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894328" 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=rs104894328" 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=RCV000019406 OR RCV000029344 OR RCV000808569" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019406, RCV000029344, RCV000808569" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019406...</a>
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<p>In a male patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#6" class="mim-tip-reference" title="Deen, P. M. T., Verdijk, M. A. J., Knoers, N. V. A. M., Wieringa, B., Monnens, L. A. H., van Os, C. H., van Oost, B. A. <strong>Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.</strong> Science 264: 92-94, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8140421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8140421</a>] [<a href="https://doi.org/10.1126/science.8140421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8140421">Deen et al. (1994)</a> identified compound heterozygosity for 2 mutations in the AQP2 gene: a 559C-T transition in exon 3, resulting in an arg187-to-cys (R187C) substitution, and a 646T-C transition in exon 4, resulting in a ser216-to-pro (S216P; <a href="#0002">107777.0002</a>) substitution. The former mutation was inherited from the father and the latter from the mother. Functional expression studies in Xenopus oocytes showed that both mutations resulted in a nonfunctional protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8140421" 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="#24" class="mim-tip-reference" title="van Lieburg, A. F., Verdijk, M. A. J., Knoers, V. V. A. M., van Essen, A. J., Proesmans, W., Mallmann, R., Monnens, L. A. H., van Oost, B. A., van Os, C. H., Deen, P. M. T. <strong>Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.</strong> Am. J. Hum. Genet. 55: 648-652, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7524315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7524315</a>]" pmid="7524315">Van Lieburg et al. (1994)</a> identified homozygosity for the R187C mutation in a Dutch patient with NDI. He was born of consanguineous parents; 3 other children in the family had died of severe dehydration and hypernatremia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7524315" 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>.0002 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894329 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894329;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894329?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894329" 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=rs104894329" 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=RCV000019407" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019407" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019407</a>
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<p>For discussion of the ser216-to-pro (S216) mutation in the AQP2 gene that was found in compound heterozygous state in a patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) by <a href="#6" class="mim-tip-reference" title="Deen, P. M. T., Verdijk, M. A. J., Knoers, N. V. A. M., Wieringa, B., Monnens, L. A. H., van Os, C. H., van Oost, B. A. <strong>Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.</strong> Science 264: 92-94, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8140421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8140421</a>] [<a href="https://doi.org/10.1126/science.8140421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8140421">Deen et al. (1994)</a>, see <a href="#0001">107777.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8140421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MOVED TO <a href="/entry/107777#0001">107777.0001</a></strong>
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<strong>.0004 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, GLY64ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894326 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894326;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894326?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894326" 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=rs104894326" 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=RCV000518067 OR RCV001274488 OR RCV001375962" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000518067, RCV001274488, RCV001375962" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000518067...</a>
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<p>In an Italian patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) whose parents were consanguineous, <a href="#24" class="mim-tip-reference" title="van Lieburg, A. F., Verdijk, M. A. J., Knoers, V. V. A. M., van Essen, A. J., Proesmans, W., Mallmann, R., Monnens, L. A. H., van Oost, B. A., van Os, C. H., Deen, P. M. T. <strong>Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.</strong> Am. J. Hum. Genet. 55: 648-652, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7524315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7524315</a>]" pmid="7524315">van Lieburg et al. (1994)</a> identified a homozygous 190G-A transition in exon 1 of the AQP2 gene, resulting in a gly64-to-arg (G64R) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7524315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, 1-BP DEL, 369C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1565636541 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565636541;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=rs1565636541" 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=rs1565636541" 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=RCV000019409 OR RCV001851943" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019409, RCV001851943" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019409...</a>
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<p>In a Palestinian patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) whose parents were consanguineous, <a href="#24" class="mim-tip-reference" title="van Lieburg, A. F., Verdijk, M. A. J., Knoers, V. V. A. M., van Essen, A. J., Proesmans, W., Mallmann, R., Monnens, L. A. H., van Oost, B. A., van Os, C. H., Deen, P. M. T. <strong>Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.</strong> Am. J. Hum. Genet. 55: 648-652, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7524315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7524315</a>]" pmid="7524315">van Lieburg et al. (1994)</a> identified homozygosity for a 1-bp deletion (369delC) in the AQP2 gene, resulting in a frameshift and premature termination after amino acid 131. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7524315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, ALA147THR
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894334 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894334;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894334?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894334" 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=rs104894334" 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=RCV000019410 OR RCV000029343 OR RCV000803130" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019410, RCV000029343, RCV000803130" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019410...</a>
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<p>In affected members of a consanguineous Austrian family with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#17" class="mim-tip-reference" title="Mulders, S. M., Knoers, N. V. A. M., van Lieburg, A. F., Monnens, L. A. H., Leumann, E., Wuhl, E., Schober, E., Rijss, J. P. L., van Os, C. H., Deen, P. M. T. <strong>New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.</strong> J. Am. Soc. Nephrol. 8: 242-248, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048343</a>] [<a href="https://doi.org/10.1681/ASN.V82242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9048343">Mulders et al. (1997)</a> identified a 533G-A transition in exon 2 of the AQP2 gene, resulting in an ala147-to-thr (A147T) substitution. The mutant AQP2 protein was functional when expressed in Xenopus oocytes, but was apparently impaired in its routing to the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9048343" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, THR126MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894330 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894330;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894330?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894330" 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=rs104894330" 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=RCV000019411 OR RCV001851944 OR RCV004798738" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019411, RCV001851944, RCV004798738" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019411...</a>
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<p>In affected members of a consanguineous family from Sri Lanka with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#17" class="mim-tip-reference" title="Mulders, S. M., Knoers, N. V. A. M., van Lieburg, A. F., Monnens, L. A. H., Leumann, E., Wuhl, E., Schober, E., Rijss, J. P. L., van Os, C. H., Deen, P. M. T. <strong>New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.</strong> J. Am. Soc. Nephrol. 8: 242-248, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048343</a>] [<a href="https://doi.org/10.1681/ASN.V82242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9048343">Mulders et al. (1997)</a> identified a 471C-T transition in exon 2 of the AQP2 gene, resulting in a thr126-to-met (T126M) substitution. The mutant AQP2 protein was functional when expressed in Xenopus oocytes, but was apparently impaired in its routing to the plasma membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9048343" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894331 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894331;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894331?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894331" 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=rs104894331" 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=RCV000019412" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019412" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019412</a>
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<p>In affected members of a consanguineous Turkish family with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#17" class="mim-tip-reference" title="Mulders, S. M., Knoers, N. V. A. M., van Lieburg, A. F., Monnens, L. A. H., Leumann, E., Wuhl, E., Schober, E., Rijss, J. P. L., van Os, C. H., Deen, P. M. T. <strong>New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.</strong> J. Am. Soc. Nephrol. 8: 242-248, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048343</a>] [<a href="https://doi.org/10.1681/ASN.V82242" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9048343">Mulders et al. (1997)</a> identified a 297A-G transition in exon 1 of the AQP2 gene, resulting in an asn68-to-ser (N68S) substitution. When expressed in oocytes, this mutant AQP2 was not functional because the substituted amino acid is part of the NPA box in loop B, which forms, together with a second NPA box in loop E, the most conserved amino acid sequence of the MIP-family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9048343" 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>.0009 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
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AQP2, GLU258LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894332 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894332;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=rs104894332" 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=rs104894332" 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=RCV000019414" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019414" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019414</a>
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<p><a href="#16" class="mim-tip-reference" title="Mulders, S. M., Bichet, D. G., Rijss, J. P. L., Kamsteeg, E.-J., Arthus, M.-F., Lonergan, M., Fujiwara, M., Morgan, K., Leijendekker, R., van der Sluijs, P., van Os, C. H., Deen, P. M. T. <strong>An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.</strong> J. Clin. Invest. 102: 57-66, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9649557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9649557</a>] [<a href="https://doi.org/10.1172/JCI2605" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9649557">Mulders et al. (1998)</a> reported the first family in which nephrogenic diabetes insipidus segregated as an autosomal dominant trait (NDI2; <a href="/entry/125800">125800</a>). An affected mother and daughter had a glu258-to-lys (E258K) mutation in the AQP2 gene. Functional expression studies showed that the mutant protein conferred only a small increase in water permeability, as a result of reduced expression at the plasma membrane. Coexpression of wildtype AQP2 with the E258K mutant revealed a dominant-negative effect on the water permeability conferred by wildtype AQP2. This effect was not seen when the wildtype protein was coexpressed with the AQP2 R187C mutant (<a href="#0001">107777.0001</a>) in recessive NDI. The physiologically important phosphorylation of ser256 by protein kinase A was not affected by the E258K mutation. Immunoblot and microscopic analyses revealed that the E258K mutant was retained in the Golgi compartment. Since AQPs are thought to tetramerize, the retention of AQP2-E258K together with wildtype AQP2 in mixed tetramers in the Golgi compartment was a likely explanation for the dominant inheritance of NDI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9649557" 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="0010" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0010 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, THR125MET
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894333 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894333;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894333?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894333" 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=rs104894333" 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=RCV000019415 OR RCV001230668" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019415, RCV001230668" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019415...</a>
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<p>In Japanese female sibs with autosomal recessive nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#9" class="mim-tip-reference" title="Goji, K., Kuwahara, M., Gu, Y., Matsuo, M., Marumo, F., Sasaki, S. <strong>Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.</strong> J. Clin. Endocr. Metab. 83: 3205-3209, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745427</a>] [<a href="https://doi.org/10.1210/jcem.83.9.5074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9745427">Goji et al. (1998)</a> identified compound heterozygosity for 2 mutations in the AQP2 gene: a 374C-T transition in exon 2, resulting in a thr125-to-met (T125M) substitution, and a 523G-A transition, resulting in a gly175-to-arg (G175R; <a href="#0011">107777.0011</a>) substitution. The water permeability of oocytes injected with wildtype complementary RNA increased 9.0-fold compared with the Pf of water-injected oocytes, whereas the increases in the Pf of oocytes injected with T125M and G175R RNA were only 1.7-fold and 1.5-fold, respectively. Immunoblot and immunocytochemistry indicated that the plasma membrane expressions of T125M and G175R AQP2 proteins were comparable to that of the wildtype, suggesting that although neither the T125M nor G175R mutation had a significant effect on plasma membrane expression, they distorted both the structure and function of the aqueous pore of AQP2. These results provided evidence that the NDI in patients with T125M and G175R mutations is attributable not to the misrouting of AQP2, but to the disrupted water channel function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745427" 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>.0011 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894335 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894335;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=rs104894335" 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=rs104894335" 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=RCV000019413" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019413" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019413</a>
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<p>For discussion of the gly175-to-arg (G175R) mutation in the AQP2 gene that was found in compound heterozygous state in 2 sibs with autosomal recessive nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) by <a href="#9" class="mim-tip-reference" title="Goji, K., Kuwahara, M., Gu, Y., Matsuo, M., Marumo, F., Sasaki, S. <strong>Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function.</strong> J. Clin. Endocr. Metab. 83: 3205-3209, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9745427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9745427</a>] [<a href="https://doi.org/10.1210/jcem.83.9.5074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9745427">Goji et al. (1998)</a>, see <a href="#0010">107777.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9745427" 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>.0012 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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AQP2, LEU22VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894336 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894336;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894336?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894336" 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=rs104894336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a female patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#2" class="mim-tip-reference" title="Canfield, M. C., Tamarappoo, B. K., Moses, A. M., Verkman, A. S., Holtzman, E. J. <strong>Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.</strong> Hum. Molec. Genet. 6: 1865-1871, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302264</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302264">Canfield et al. (1997)</a> identified compound heterozygosity for 2 mutations in the AQP2 gene: a leu22-to-val (L22V) substitution in exon 1, and a cys181-to-trp (C181W; <a href="#0013">107777.0013</a>) substitution in exon 3. The patient had symptoms dating from infancy. She responded to large doses of desmopressin, which decreased urine volume from 10 to 4 liters per day. Neither her parents nor her 3 sisters were polyuric. Residue cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near the NPA motif conserved in all aquaporins. Osmotic water permeability in Xenopus oocytes injected with cRNA encoding the mutant C181W AQP2 protein was not increased over water control, while expression of L22V cRNA increased the osmotic water permeability to approximately 60% of that for wildtype AQP2. Coinjection of the mutant cRNAs with the wildtype cRNA did not affect the function of the wildtype AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wildtype AQP2 showed endosome and plasma membrane staining. <a href="#2" class="mim-tip-reference" title="Canfield, M. C., Tamarappoo, B. K., Moses, A. M., Verkman, A. S., Holtzman, E. J. <strong>Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.</strong> Hum. Molec. Genet. 6: 1865-1871, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302264</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302264">Canfield et al. (1997)</a> concluded that AQP2 mutations can confer partially responsive nephrogenic diabetes insipidus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302264" 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>.0013 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894337 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894337;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894337?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894337" 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=rs104894337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the cys181-to-trp (C181W) mutation in the AQP2 gene that was found in compound heterozygous state in a patient with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) by <a href="#2" class="mim-tip-reference" title="Canfield, M. C., Tamarappoo, B. K., Moses, A. M., Verkman, A. S., Holtzman, E. J. <strong>Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.</strong> Hum. Molec. Genet. 6: 1865-1871, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302264</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302264">Canfield et al. (1997)</a>, see <a href="#0012">107777.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302264" 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>.0014 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1565637179 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565637179;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=rs1565637179" 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=rs1565637179" 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=RCV000019418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019418</a>
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<p><a href="#12" class="mim-tip-reference" title="Kuwahara, M., Iwai, K., Ooeda, T., Igarashi, T., Ogawa, E., Katsushima, Y., Shinbo, I., Uchida, S., Terada, Y., Arthus, M.-F., Lonergan, M., Fujiwara, T. M., Bichet, D. G., Marumo, F., Sasaki, S. <strong>Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.</strong> Am. J. Hum. Genet. 69: 738-748, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11536078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11536078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11536078[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/10.1086/323643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11536078">Kuwahara et al. (2001)</a> identified a 1-bp deletion (721delG) in the AQP2 gene as a cause of autosomal dominant nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>). The mutation resulted in a frameshift and an elongated protein with a C-terminal tail of 61 additional amino acids. Elongation of the C-terminal tail resulted in impaired trafficking of the mutant AQP2, and a dominant-negative effect was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11536078" 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>.0015 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1565637189 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1565637189;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=rs1565637189" 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=rs1565637189" 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=RCV000019419" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019419" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019419</a>
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<p>In a 3-generation family with autosomal dominant inheritance of nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#14" class="mim-tip-reference" title="Marr, N., Bichet, D. G., Lonergan, M., Arthus, M.-F., Jeck, N., Seyberth, H. W., Rosenthal, W., van Os, C. H., Oksche, A., Deen, P. M. T. <strong>Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.</strong> Hum. Molec. Genet. 11: 779-789, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929850</a>] [<a href="https://doi.org/10.1093/hmg/11.7.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11929850">Marr et al. (2002)</a> identified a 1-bp deletion (727delG) in the AQP2 gene. The predicted mutant protein had an altered and extended C-terminal tail. When expressed in renal epithelial cells, the mutant protein predominantly localized to the basolateral membrane and late endosomes/lysosomes, whereas wildtype AQP2 was expressed in the apical membrane. When coexpressed, wildtype AQP2 and AQP2-727G formed heterooligomers that mainly colocalized to late endosomes/lysosomes. The cells showed reduced water permeability due to reduced plasma membrane expression of wildtype AQP2. On the basis of their own data and the data of <a href="#12" class="mim-tip-reference" title="Kuwahara, M., Iwai, K., Ooeda, T., Igarashi, T., Ogawa, E., Katsushima, Y., Shinbo, I., Uchida, S., Terada, Y., Arthus, M.-F., Lonergan, M., Fujiwara, T. M., Bichet, D. G., Marumo, F., Sasaki, S. <strong>Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.</strong> Am. J. Hum. Genet. 69: 738-748, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11536078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11536078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11536078[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/10.1086/323643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11536078">Kuwahara et al. (2001)</a> (see <a href="#0014">107777.0014</a>), <a href="#14" class="mim-tip-reference" title="Marr, N., Bichet, D. G., Lonergan, M., Arthus, M.-F., Jeck, N., Seyberth, H. W., Rosenthal, W., van Os, C. H., Oksche, A., Deen, P. M. T. <strong>Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.</strong> Hum. Molec. Genet. 11: 779-789, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929850</a>] [<a href="https://doi.org/10.1093/hmg/11.7.779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11929850">Marr et al. (2002)</a> hypothesized that misrouting, rather than lack of function, may be a general mechanism for the 'loss of function' phenotype in dominant NDI. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11536078+11929850" 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>.0016 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28931580 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931580;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28931580?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28931580" 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=rs28931580" 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=RCV000019420 OR RCV001039718" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019420, RCV001039718" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019420...</a>
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<p>In affected members from 2 Chinese families with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>), <a href="#13" class="mim-tip-reference" title="Lin, S.-H., Bichet, D.G., Sasaki, S., Kuwahara, M., Arthus, M.-F., Lonergan, M., Lin, Y.-F. <strong>Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families.</strong> J. Clin. Endocr. Metab. 87: 2694-2700, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050236</a>] [<a href="https://doi.org/10.1210/jcem.87.6.8617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12050236">Lin et al. (2002)</a> identified compound heterozygosity for 2 mutations in exon 1 of the AQP2 gene: a 170A-C transversion, resulting in a gln57-to-pro (Q57P) substitution, and a 299G-T transversion, resulting in a gly100-to-val (G100V; <a href="#0017">107777.0017</a>) substitution. Expression of the Q57P and G100V AQP2 proteins showed an only 1.3-fold and 1.2-fold increase, respectively, in the water permeability in contrast to an 8.0-fold increase in oocytes injected with wildtype cRNA. The results provided evidence that the Q57P and G100V mutations in congenital nephrogenic diabetes insipidus are attributable to the misrouting of AQP2. The patients showed normal hypotensive and coagulation responses following the administration of desamino-8-D-arginine AVP, a clinical suggestion of normal vasopressin-2 receptors (V2R; <a href="/entry/300538">300538</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894338;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894338?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894338" 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=rs104894338" 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=RCV000019421 OR RCV001851945" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019421, RCV001851945" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019421...</a>
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<p>For discussion of the gly100-to-val (G100V) mutation in the AQP2 gene that was found in compound heterozygous state in affected individuals from 2 families with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) by <a href="#13" class="mim-tip-reference" title="Lin, S.-H., Bichet, D.G., Sasaki, S., Kuwahara, M., Arthus, M.-F., Lonergan, M., Lin, Y.-F. <strong>Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families.</strong> J. Clin. Endocr. Metab. 87: 2694-2700, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050236</a>] [<a href="https://doi.org/10.1210/jcem.87.6.8617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12050236">Lin et al. (2002)</a>, see <a href="#0016">107777.0016</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs104894339 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894339;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs104894339?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894339" 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=rs104894339" 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=RCV000019422 OR RCV000799304" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019422, RCV000799304" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019422...</a>
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<p><a href="#4" class="mim-tip-reference" title="de Mattia, F., Savelkoul, P. J. M., Bichet, D. G., Kamsteeg, E.-J., Konings, I. B. M., Marr, N., Arthus, M.-F., Lonergan, M., van Os, C. H., van der Sluijs, P., Robertson, G., Deen, P. M. T. <strong>A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.</strong> Hum. Molec. Genet. 13: 3045-3056, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509592</a>] [<a href="https://doi.org/10.1093/hmg/ddh339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509592">De Mattia et al. (2004)</a> described 2 families with autosomal recessive nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) in which affected individuals were compound heterozygous for a 785C-T transition in the AQP2 gene, resulting in a pro262-to-leu (P262L) substitution in the C-terminal tail, and either a 568G-A transition in the AQP2 gene, resulting in an ala190-to-thr (A190T; <a href="#0019">107777.0019</a>) substitution, or an R187C (<a href="#0001">107777.0001</a>) substitution, respectively. Upon expression in oocytes, P262L AQP2 protein properly folded and was functional in contrast to the R187C and A190T proteins. In polarized epithelial cells, P262L protein was retained in intracellular vesicles and did not localize to the ER. Upon coexpression with wildtype AQP2, P262L protein interacted with wildtype AQP2, and the resulting heterotetramer properly localized to the apical membrane. <a href="#4" class="mim-tip-reference" title="de Mattia, F., Savelkoul, P. J. M., Bichet, D. G., Kamsteeg, E.-J., Konings, I. B. M., Marr, N., Arthus, M.-F., Lonergan, M., van Os, C. H., van der Sluijs, P., Robertson, G., Deen, P. M. T. <strong>A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.</strong> Hum. Molec. Genet. 13: 3045-3056, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509592</a>] [<a href="https://doi.org/10.1093/hmg/ddh339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509592">De Mattia et al. (2004)</a> concluded that P262L would act as a mutant in autosomal dominant NDI, except that its missorting is overruled by apical sorting of wildtype AQP2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15509592" 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>.0019 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894341 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894341;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=rs104894341" 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=rs104894341" 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=RCV000019423 OR RCV004782019" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019423, RCV004782019" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019423...</a>
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<p>For discussion of the ala190-to-thr (A190T) mutation in the AQP2 gene that was found in compound heterozygous state in affected individuals from 2 families with nephrogenic diabetes insipidus (NDI2; <a href="/entry/125800">125800</a>) by <a href="#4" class="mim-tip-reference" title="de Mattia, F., Savelkoul, P. J. M., Bichet, D. G., Kamsteeg, E.-J., Konings, I. B. M., Marr, N., Arthus, M.-F., Lonergan, M., van Os, C. H., van der Sluijs, P., Robertson, G., Deen, P. M. T. <strong>A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.</strong> Hum. Molec. Genet. 13: 3045-3056, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509592</a>] [<a href="https://doi.org/10.1093/hmg/ddh339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509592">De Mattia et al. (2004)</a>, see <a href="#0018">107777.0018</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15509592" 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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Bouley, R., Breton, S., Sun, T., McLaughlin, M., Nsumu, N. N., Lin, H. Y., Ausiello, D. A., Brown, D.
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<strong>Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells.</strong>
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J. Clin. Invest. 106: 1115-1126, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11067864/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11067864</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11067864[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=11067864" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI9594" target="_blank">Full Text</a>]
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Canfield, M. C., Tamarappoo, B. K., Moses, A. M., Verkman, A. S., Holtzman, E. J.
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<strong>Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.</strong>
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Hum. Molec. Genet. 6: 1865-1871, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302264</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.11.1865" target="_blank">Full Text</a>]
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Carroll, P., Al-Mojalli, H., Al-Abbad, A., Al-Hassoun, I., Al-Hamed, M., Al-Amr, R., Butt, A. I., Meyer, B. F.
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<strong>Novel mutations underlying nephrogenic diabetes insipidus in Arab families.</strong>
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Genet. Med. 8: 443-447, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16845277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16845277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16845277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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de Mattia, F., Savelkoul, P. J. M., Bichet, D. G., Kamsteeg, E.-J., Konings, I. B. M., Marr, N., Arthus, M.-F., Lonergan, M., van Os, C. H., van der Sluijs, P., Robertson, G., Deen, P. M. T.
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<strong>A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.</strong>
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Hum. Molec. Genet. 13: 3045-3056, 2004.
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[<a href="https://doi.org/10.1093/hmg/ddh339" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.8140421" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/11.7.779" target="_blank">Full Text</a>]
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<strong>Urinary excretion of aquaporin-2 water channel differentiates psychogenic polydipsia from central diabetes insipidus.</strong>
|
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J. Clin. Endocr. Metab. 84: 2235-2237, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10372737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10372737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10372737" 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/10.1210/jcem.84.6.5715" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Saito1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saito, T., Ishikawa, S.-E., Sasaki, S., Nakamura, T., Rokkaku, K., Kawakami, A., Honda, K., Marumo, F., Saito, T.
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<strong>Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.</strong>
|
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J. Clin. Endocr. Metab. 82: 1823-1827, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9177390/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9177390</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9177390" 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/10.1210/jcem.82.6.3984" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Sasaki1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sasaki, S., Fushimi, K., Saito, H., Saito, F., Uchida, S., Ishibashi, K., Kuwahara, M., Ikeuchi, T., Inui, K., Nakajima, K., Watanabe, T. X., Marumo, F.
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<strong>Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.</strong>
|
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J. Clin. Invest. 93: 1250-1256, 1994. Note: Erratum: J. Clin. Invest. 94: following 216, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7510718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7510718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7510718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI117079" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Sasaki1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sasaki, S., Saito, H., Saito, F., Fushimi, K., Uchida, S., Rai, Y., Ikeuchi, T., Inui, K., Marumo, F.
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<strong>Cloning, expression and chromosomal mapping of human collecting duct water channel (hWCH-CD). (Abstract)</strong>
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J. Am. Soc. Nephrol. 4: 858 only, 1993.
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</p>
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="van Lieburg1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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van Lieburg, A. F., Verdijk, M. A. J., Knoers, V. V. A. M., van Essen, A. J., Proesmans, W., Mallmann, R., Monnens, L. A. H., van Oost, B. A., van Os, C. H., Deen, P. M. T.
|
|
<strong>Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.</strong>
|
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Am. J. Hum. Genet. 55: 648-652, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7524315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7524315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7524315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Yang2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, B., Gillespie, A., Carlson, E. J., Epstein, C. J., Verkman, A. S.
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<strong>Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus.</strong>
|
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J. Biol. Chem. 276: 2775-2779, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11035038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11035038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11035038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M008216200" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 7/25/2007
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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George E. Tiller - updated : 5/21/2007<br>Patricia A. Hartz - updated : 6/14/2006<br>Patricia A. Hartz - updated : 6/2/2006<br>Cassandra L. Kniffin - reorganized : 8/5/2005<br>Patricia A. Hartz - updated : 6/13/2003<br>John A. Phillips, III - updated : 1/9/2003<br>George E. Tiller - updated : 10/28/2002<br>Victor A. McKusick - updated : 10/17/2001<br>John A. Phillips, III - updated : 9/20/2001<br>Paul J. Converse - updated : 4/9/2001<br>Ada Hamosh - updated : 3/14/2000<br>John A. Phillips, III - updated : 3/7/2000<br>John A. Phillips, III - updated : 3/2/1999<br>Victor A. McKusick - updated : 9/3/1998<br>John A. Phillips, III - updated : 8/5/1997<br>Beat Steinmann - updated : 4/28/1997
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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="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 11/5/1993
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</span>
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</div>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/24/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/23/2021<br>carol : 08/05/2016<br>carol : 07/22/2015<br>carol : 7/22/2015<br>mcolton : 7/21/2015<br>carol : 9/18/2013<br>carol : 9/18/2013<br>terry : 11/27/2012<br>alopez : 8/2/2007<br>alopez : 8/2/2007<br>terry : 7/25/2007<br>wwang : 6/1/2007<br>terry : 5/21/2007<br>mgross : 6/15/2006<br>terry : 6/14/2006<br>mgross : 6/6/2006<br>terry : 6/2/2006<br>carol : 8/24/2005<br>carol : 8/5/2005<br>ckniffin : 5/23/2005<br>mgross : 6/13/2003<br>alopez : 1/9/2003<br>cwells : 10/28/2002<br>carol : 11/5/2001<br>mcapotos : 10/25/2001<br>mcapotos : 10/24/2001<br>terry : 10/17/2001<br>cwells : 9/28/2001<br>cwells : 9/20/2001<br>mgross : 4/9/2001<br>alopez : 3/20/2000<br>alopez : 3/15/2000<br>terry : 3/14/2000<br>mgross : 3/7/2000<br>mgross : 3/11/1999<br>mgross : 3/2/1999<br>mgross : 3/2/1999<br>alopez : 9/14/1998<br>carol : 9/3/1998<br>dkim : 6/30/1998<br>mark : 9/1/1997<br>jenny : 8/5/1997<br>jenny : 7/9/1997<br>joanna : 4/28/1997<br>joanna : 4/28/1997<br>terry : 10/25/1995<br>mark : 8/21/1995<br>carol : 3/3/1995<br>jason : 6/28/1994<br>carol : 11/5/1993
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</span>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 107777
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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AQUAPORIN 2; AQP2
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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AQUAPORIN-CD
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: AQP2</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 12q13.12
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:49,950,737-49,958,878 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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12q13.12
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</span>
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</td>
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<td>
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<span class="mim-font">
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Diabetes insipidus, nephrogenic, 2
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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125800
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The AQP2 gene encodes an aquaporin-2 water channel located in the renal collecting tubules. Aquaporin-CHIP (AQP1; 107776) is located in the proximal renal tubule (Fushimi et al., 1993). </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Fushimi et al. (1993) cloned the cDNA for the water channel of the apical membrane of the kidney collecting tubule in the rat. The gene shows 42% identity in amino acid sequence to AQP1. Expression in Xenopus oocytes markedly increased osmotic water permeability (Pf). The functional expression and the limited localization suggested that AQP2 is the vasopressin-regulated water channel. Fushimi et al. (1993) referred to AQP2 as WCH-CD, for 'water channel-collecting duct.' </p><p>Sasaki et al. (1993, 1994) cloned a cDNA for human AQP2 and found that it encodes a deduced protein with 91% amino acid identity to the rat protein. By screening kidney cDNA in cosmid libraries with a rat AQP2 cDNA probe, Deen et al. (1994) isolated human AQP2. They found that the predicted amino acid sequence shares 89.7% identity with the rat protein. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nielsen et al. (1995) showed that arginine vasopressin (AVP; 192340) increases cellular water permeability by inducing exocytosis of AQP2-laden vesicles, transferring water channels from intracellular vesicles to the apical plasma membrane. </p><p>Using rat kidney slices and porcine kidney cells stably expressing rat Aqp2, Bouley et al. (2000) demonstrated that AQP2 trafficking can be stimulated by cAMP-independent pathways that utilize nitric oxide (NO). The NO donors sodium nitroprusside (SNP) and NONOate and the NO synthase (see 163731) substrate L-arginine mimicked the effect of vasopressin (VP), stimulating relocation of Aqp2 from cytoplasmic vesicles to the apical plasma membrane. SNP increased intracellular cGMP rather than cAMP, and exogenous cGMP stimulated AQP2 membrane insertion. Atrial natriuretic factor (108780), which signals via cGMP, also stimulated AQP2 translocation. Both the VP and SNP effects were blocked by a kinase inhibitor, and membrane insertion was blocked in cells expressing the phosphorylation-deficient mutant ser256 to ala, indicating that ser256 is required for signaling. </p><p>Kanno et al. (1995) reported that aquaporin-2 is detectable in the urine in both soluble and membrane-bound forms. In normal subjects, an infusion of desmopressin increased the urinary excretion of aquaporin-2. In 5 patients with central diabetes insipidus (CDI; 125700), administration of desmopressin increased urinary excretion of aquaporin-2; however, this response was not seen in 4 patients with X-linked (NDI1; 304800) or autosomal recessive nephrogenic diabetes insipidus (NDI2; 125800). Saito et al. (1997) determined that measuring urinary excretion of AQP2 is of value in diagnosing central diabetes insipidus. In normal subjects under ad libitum water drinking, urinary AQP2 was positively correlated with plasma arginine vasopressin levels, but not with urinary osmolality. Saito et al. (1997) found that measurement of AQP2 was also helpful when using a hypertonic saline infusion to diagnose CDI. Saito et al. (1999) investigated whether urinary excretion of AQP2 under ad libitum water intake was of value in the differentiation between psychogenic polydipsia and CDI. A 30-minute urine collection was made at 0900 hours in 3 groups: 11 patients with CDI (22 to 68 years old), 10 patients with psychogenic polydipsia (28 to 60 years old), and 15 normal subjects (21 to 38 years old). In the patients with CDI, the plasma arginine vasopressin level was low despite hyperosmolality, resulting in hypotonic urine. Urinary excretion of AQP2 was 37 +/- 15 fmol/mg creatinine, a value one-fifth less than that in the normal subjects. In the patients with psychogenic polydipsia, plasma arginine vasopressin and urinary osmolality were as low as those in the patients with CDI. However, urinary excretion of AQP2 of 187 +/- 45 fmol/mg creatinine was not decreased, and its excretion was equal to that in the normal subjects. The results indicated that urinary excretion of AQP2, under ad libitum water drinking, participates in the differentiation of psychogenic polydipsia from CDI. </p><p>Ishikawa et al. (2001) undertook to determine whether urinary excretion of AQP2 participates in the involvement of arginine vasopressin in hyponatremia less than 130 mmol/L in 33 elderly subjects more than 64 years of age during the last 5-year period. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP2 and antidiuresis. Plasma AVP and urinary excretion of AQP2 were not reduced after an acute water load test. The inappropriate secretion of AVP was evident in the patients with the syndrome of inappropriate secretion of diuretic hormone (SIADH) and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP2 and renal water excretion in those with hypopituitarism. The authors concluded that urinary excretion of AQP2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects. </p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By in situ hybridization, Sasaki et al. (1993, 1994) mapped the AQP2 gene to chromosome 12q13, very close to the site of major intrinsic protein (MIP; 154050). The investigators suggested that a defect in the AQP2 gene is the basis of the autosomal form of nephrogenic diabetes insipidus (NDI2; 125800). </p><p>Deen et al. (1994) used fluorescence in situ hybridization to map the AQP2 gene to chromosome 12. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a male patient with autosomal recessive nephrogenic diabetes insipidus (NDI2; 125800), Deen et al. (1994) identified compound heterozygosity for 2 mutations in the AQP2 gene (R187C, 107777.0001 and S216P, 107777.0002). Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Deen et al. (1995) found that expression of 3 mutant AQP2 proteins, R187C, S216P, and G64R (107777.0004), in Xenopus oocytes resulted in nonfunctional water channels. The transcripts encoding the missense AQPs were translated as efficiently as wildtype transcript and were equally stable. Immunocytochemistry demonstrated that the mutant AQP2 did not label in the plasma membrane. The authors proposed that the inability of the AQP2 proteins to facilitate water transport was caused by an impaired routing to the plasma membrane. </p><p>Missense mutations and a single-nucleotide deletion in the AQP2 gene were found by van Lieburg et al. (1994) in 3 NDI patients from consanguineous families (107777.0001; 107777.0004-107777.0005). Expression studies in Xenopus oocytes showed that the mutated AQP2 proteins were nonfunctional. Mulders et al. (1997) reported 3 additional NDI patients who were homozygous for mutations in the AQP2 gene. Functional expression studies showed that 2 of the mutations (107777.0006 and 107777.0007) resulted in functional proteins that were apparently retained in the endoplasmic reticulum and impaired in their routing to the plasma membrane. </p><p>In a study of a Dutch family with autosomal dominant NDI, Mulders et al. (1998) identified a mutation (107777.0009) in the AQP2 gene that exhibited a dominant-negative effect. </p><p>In affected members of 3 unrelated families with autosomal dominant NDI, Kuwahara et al. (2001) identified 3 different deletion mutations in exon 4 of the AQP2 gene (see, e.g., 107777.0014), all of which resulted in an elongated protein with a C-terminal tail of 61 amino acids. The predicted wildtype AQP2 protein contains 271 amino acids, whereas the predicted mutant proteins contained 330 to 333 amino acids because of the frameshift. In Xenopus oocytes injected with mutant AQP2 cRNAs, the osmotic water permeability was much smaller than that of oocytes with the AQP2 wildtype (14 to 17%). The results suggested that the trafficking of mutant AQP2 was impaired due to elongation of the C-terminal tail. The dominant-negative effect was attributed to oligomerization of the wildtype and mutant AQP2s. Marr et al. (2002) reported similar findings (see 107777.0015). </p><p>Carroll et al. (2006) identified the molecular basis of NDI in Arab families. Two novel missense mutations were identified in AQP2. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Yang et al. (2001) generated a mouse knockin model of NDI generated by targeted gene replacement with the thr126-to-met mutation (T126M; 107777.0007) along with mutations to preserve the consensus sequence for N-linked glycosylation found in human AQP2. The mutant mice died within 6 days after birth unless given supplemental fluid. Urine/serum analysis showed a urinary concentrating defect with serum hyperosmolality and low urine osmolality that could not be corrected by a V2 vasopressin agonist. Northern blot analysis revealed upregulated Aqp2-T126M transcripts identical in size to wildtype Aqp2. Immunoblot analysis indicated complex glycosylation of wildtype Aqp2 but endoglycosidase H-sensitive core glycosylation of the mutant, suggesting ER retention. Immunohistologic and histologic analyses revealed kidney collecting duct dilatation, papillary atrophy, and some plasma membrane Aqp2 expression. Yang et al. (2001) concluded that the Aqp2-T126M mutant creates a more severe phenotype than those observed in mice lacking water channels Aqp1, Aqp3 (600170), or Aqp4 (600308), and establishes a mouse model of human autosomal NDI. </p><p>Rojek et al. (2006) found that Aqp2-null mice appeared normal at birth but failed to thrive and died within 2 weeks of age. Kidneys from Aqp2-null pups showed papillary atrophy and signs of hydronephrosis. Mice with Aqp2 knockout targeted to the renal collecting ducts survived to adulthood, but they showed decreased body weight, 10-fold increased urine production, and decreased urinary osmolality and were unable to adapt to water deprivation. Rojek et al. (2006) concluded that AQP2 expression in kidney connecting tubules is sufficient for survival and that AQP2 expression in collecting ducts is required to regulate body water balance. </p><p>Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation that causes severe hydronephrosis and obstructive nephropathy in mice. McDill et al. (2006) found that homozygous cph mice were born at mendelian ratios and appeared grossly normal at birth, but they grew slowly and showed significant size and weight differences from postnatal day 8 onward. About 90% of cph mice died between 2 and 4 weeks of age. By 2 weeks, most had visibly enlarged abdomens and appeared lethargic. McDill et al. (2006) identified a ser256-to-leu (S256L) mutation in the Aqp2 gene as the cause of cph. The S256L substitution in the cytoplasmic tail of the Aqp2 protein prevented phosphorylation at S256 and the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct principal cells. The interference with normal trafficking of Aqp2 by the S256L mutation resulted in a severe urine concentration defect. The NDI symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery before the onset of hydronephrosis suggested that the congenital obstructive nephropathy was likely the result of the polyuria. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>19 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</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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AQP2, ARG187CYS
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<br />
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SNP: rs104894328,
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gnomAD: rs104894328,
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ClinVar: RCV000019406, RCV000029344, RCV000808569
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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 male patient with nephrogenic diabetes insipidus (NDI2; 125800), Deen et al. (1994) identified compound heterozygosity for 2 mutations in the AQP2 gene: a 559C-T transition in exon 3, resulting in an arg187-to-cys (R187C) substitution, and a 646T-C transition in exon 4, resulting in a ser216-to-pro (S216P; 107777.0002) substitution. The former mutation was inherited from the father and the latter from the mother. Functional expression studies in Xenopus oocytes showed that both mutations resulted in a nonfunctional protein. </p><p>Van Lieburg et al. (1994) identified homozygosity for the R187C mutation in a Dutch patient with NDI. He was born of consanguineous parents; 3 other children in the family had died of severe dehydration and hypernatremia. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0002 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</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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AQP2, SER216PRO
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<br />
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SNP: rs104894329,
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gnomAD: rs104894329,
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ClinVar: RCV000019407
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the ser216-to-pro (S216) mutation in the AQP2 gene that was found in compound heterozygous state in a patient with nephrogenic diabetes insipidus (NDI2; 125800) by Deen et al. (1994), see 107777.0001. </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-text-font">
|
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<strong>.0003 MOVED TO 107777.0001</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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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</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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AQP2, GLY64ARG
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<br />
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SNP: rs104894326,
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gnomAD: rs104894326,
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ClinVar: RCV000518067, RCV001274488, RCV001375962
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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 an Italian patient with nephrogenic diabetes insipidus (NDI2; 125800) whose parents were consanguineous, van Lieburg et al. (1994) identified a homozygous 190G-A transition in exon 1 of the AQP2 gene, resulting in a gly64-to-arg (G64R) substitution. </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>.0005 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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AQP2, 1-BP DEL, 369C
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<br />
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SNP: rs1565636541,
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ClinVar: RCV000019409, RCV001851943
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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 Palestinian patient with nephrogenic diabetes insipidus (NDI2; 125800) whose parents were consanguineous, van Lieburg et al. (1994) identified homozygosity for a 1-bp deletion (369delC) in the AQP2 gene, resulting in a frameshift and premature termination after amino acid 131. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
AQP2, ALA147THR
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|
<br />
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|
|
SNP: rs104894334,
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|
|
|
gnomAD: rs104894334,
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|
|
|
|
|
ClinVar: RCV000019410, RCV000029343, RCV000803130
|
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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 affected members of a consanguineous Austrian family with nephrogenic diabetes insipidus (NDI2; 125800), Mulders et al. (1997) identified a 533G-A transition in exon 2 of the AQP2 gene, resulting in an ala147-to-thr (A147T) substitution. The mutant AQP2 protein was functional when expressed in Xenopus oocytes, but was apparently impaired in its routing to the plasma membrane. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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AQP2, THR126MET
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<br />
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|
|
SNP: rs104894330,
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|
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gnomAD: rs104894330,
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|
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ClinVar: RCV000019411, RCV001851944, RCV004798738
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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 affected members of a consanguineous family from Sri Lanka with nephrogenic diabetes insipidus (NDI2; 125800), Mulders et al. (1997) identified a 471C-T transition in exon 2 of the AQP2 gene, resulting in a thr126-to-met (T126M) substitution. The mutant AQP2 protein was functional when expressed in Xenopus oocytes, but was apparently impaired in its routing to the plasma membrane. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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AQP2, ASN68SER
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<br />
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|
|
SNP: rs104894331,
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gnomAD: rs104894331,
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ClinVar: RCV000019412
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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 affected members of a consanguineous Turkish family with nephrogenic diabetes insipidus (NDI2; 125800), Mulders et al. (1997) identified a 297A-G transition in exon 1 of the AQP2 gene, resulting in an asn68-to-ser (N68S) substitution. When expressed in oocytes, this mutant AQP2 was not functional because the substituted amino acid is part of the NPA box in loop B, which forms, together with a second NPA box in loop E, the most conserved amino acid sequence of the MIP-family. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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AQP2, GLU258LYS
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<br />
|
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|
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SNP: rs104894332,
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|
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ClinVar: RCV000019414
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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>Mulders et al. (1998) reported the first family in which nephrogenic diabetes insipidus segregated as an autosomal dominant trait (NDI2; 125800). An affected mother and daughter had a glu258-to-lys (E258K) mutation in the AQP2 gene. Functional expression studies showed that the mutant protein conferred only a small increase in water permeability, as a result of reduced expression at the plasma membrane. Coexpression of wildtype AQP2 with the E258K mutant revealed a dominant-negative effect on the water permeability conferred by wildtype AQP2. This effect was not seen when the wildtype protein was coexpressed with the AQP2 R187C mutant (107777.0001) in recessive NDI. The physiologically important phosphorylation of ser256 by protein kinase A was not affected by the E258K mutation. Immunoblot and microscopic analyses revealed that the E258K mutant was retained in the Golgi compartment. Since AQPs are thought to tetramerize, the retention of AQP2-E258K together with wildtype AQP2 in mixed tetramers in the Golgi compartment was a likely explanation for the dominant inheritance of NDI. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0010 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</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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AQP2, THR125MET
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<br />
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SNP: rs104894333,
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gnomAD: rs104894333,
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ClinVar: RCV000019415, RCV001230668
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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 Japanese female sibs with autosomal recessive nephrogenic diabetes insipidus (NDI2; 125800), Goji et al. (1998) identified compound heterozygosity for 2 mutations in the AQP2 gene: a 374C-T transition in exon 2, resulting in a thr125-to-met (T125M) substitution, and a 523G-A transition, resulting in a gly175-to-arg (G175R; 107777.0011) substitution. The water permeability of oocytes injected with wildtype complementary RNA increased 9.0-fold compared with the Pf of water-injected oocytes, whereas the increases in the Pf of oocytes injected with T125M and G175R RNA were only 1.7-fold and 1.5-fold, respectively. Immunoblot and immunocytochemistry indicated that the plasma membrane expressions of T125M and G175R AQP2 proteins were comparable to that of the wildtype, suggesting that although neither the T125M nor G175R mutation had a significant effect on plasma membrane expression, they distorted both the structure and function of the aqueous pore of AQP2. These results provided evidence that the NDI in patients with T125M and G175R mutations is attributable not to the misrouting of AQP2, but to the disrupted water channel function. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0011 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</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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AQP2, GLY175ARG
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<br />
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SNP: rs104894335,
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ClinVar: RCV000019413
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the gly175-to-arg (G175R) mutation in the AQP2 gene that was found in compound heterozygous state in 2 sibs with autosomal recessive nephrogenic diabetes insipidus (NDI2; 125800) by Goji et al. (1998), see 107777.0010. </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>.0012 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
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</h4>
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|
</div>
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<div>
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<span class="mim-text-font">
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AQP2, LEU22VAL
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<br />
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SNP: rs104894336,
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gnomAD: rs104894336,
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ClinVar: RCV000019416
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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 female patient with nephrogenic diabetes insipidus (NDI2; 125800), Canfield et al. (1997) identified compound heterozygosity for 2 mutations in the AQP2 gene: a leu22-to-val (L22V) substitution in exon 1, and a cys181-to-trp (C181W; 107777.0013) substitution in exon 3. The patient had symptoms dating from infancy. She responded to large doses of desmopressin, which decreased urine volume from 10 to 4 liters per day. Neither her parents nor her 3 sisters were polyuric. Residue cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near the NPA motif conserved in all aquaporins. Osmotic water permeability in Xenopus oocytes injected with cRNA encoding the mutant C181W AQP2 protein was not increased over water control, while expression of L22V cRNA increased the osmotic water permeability to approximately 60% of that for wildtype AQP2. Coinjection of the mutant cRNAs with the wildtype cRNA did not affect the function of the wildtype AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wildtype AQP2 showed endosome and plasma membrane staining. Canfield et al. (1997) concluded that AQP2 mutations can confer partially responsive nephrogenic diabetes insipidus. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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AQP2, CYS181TRP
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<br />
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|
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SNP: rs104894337,
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|
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|
|
gnomAD: rs104894337,
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|
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|
|
ClinVar: RCV000019417
|
|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the cys181-to-trp (C181W) mutation in the AQP2 gene that was found in compound heterozygous state in a patient with nephrogenic diabetes insipidus (NDI2; 125800) by Canfield et al. (1997), see 107777.0012. </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>
|
|
<span class="mim-font">
|
|
<strong>.0014 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, 1-BP DEL, 721G
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|
|
<br />
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|
|
SNP: rs1565637179,
|
|
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|
|
|
|
ClinVar: RCV000019418
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kuwahara et al. (2001) identified a 1-bp deletion (721delG) in the AQP2 gene as a cause of autosomal dominant nephrogenic diabetes insipidus (NDI2; 125800). The mutation resulted in a frameshift and an elongated protein with a C-terminal tail of 61 additional amino acids. Elongation of the C-terminal tail resulted in impaired trafficking of the mutant AQP2, and a dominant-negative effect was observed. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, 1-BP DEL, 727G
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|
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<br />
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|
|
SNP: rs1565637189,
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|
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|
|
|
|
|
ClinVar: RCV000019419
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3-generation family with autosomal dominant inheritance of nephrogenic diabetes insipidus (NDI2; 125800), Marr et al. (2002) identified a 1-bp deletion (727delG) in the AQP2 gene. The predicted mutant protein had an altered and extended C-terminal tail. When expressed in renal epithelial cells, the mutant protein predominantly localized to the basolateral membrane and late endosomes/lysosomes, whereas wildtype AQP2 was expressed in the apical membrane. When coexpressed, wildtype AQP2 and AQP2-727G formed heterooligomers that mainly colocalized to late endosomes/lysosomes. The cells showed reduced water permeability due to reduced plasma membrane expression of wildtype AQP2. On the basis of their own data and the data of Kuwahara et al. (2001) (see 107777.0014), Marr et al. (2002) hypothesized that misrouting, rather than lack of function, may be a general mechanism for the 'loss of function' phenotype in dominant NDI. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, GLN57PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931580,
|
|
|
|
|
|
gnomAD: rs28931580,
|
|
|
|
|
|
ClinVar: RCV000019420, RCV001039718
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members from 2 Chinese families with nephrogenic diabetes insipidus (NDI2; 125800), Lin et al. (2002) identified compound heterozygosity for 2 mutations in exon 1 of the AQP2 gene: a 170A-C transversion, resulting in a gln57-to-pro (Q57P) substitution, and a 299G-T transversion, resulting in a gly100-to-val (G100V; 107777.0017) substitution. Expression of the Q57P and G100V AQP2 proteins showed an only 1.3-fold and 1.2-fold increase, respectively, in the water permeability in contrast to an 8.0-fold increase in oocytes injected with wildtype cRNA. The results provided evidence that the Q57P and G100V mutations in congenital nephrogenic diabetes insipidus are attributable to the misrouting of AQP2. The patients showed normal hypotensive and coagulation responses following the administration of desamino-8-D-arginine AVP, a clinical suggestion of normal vasopressin-2 receptors (V2R; 300538). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, GLY100VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894338,
|
|
|
|
|
|
gnomAD: rs104894338,
|
|
|
|
|
|
ClinVar: RCV000019421, RCV001851945
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gly100-to-val (G100V) mutation in the AQP2 gene that was found in compound heterozygous state in affected individuals from 2 families with nephrogenic diabetes insipidus (NDI2; 125800) by Lin et al. (2002), see 107777.0016. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, PRO262LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894339,
|
|
|
|
|
|
gnomAD: rs104894339,
|
|
|
|
|
|
ClinVar: RCV000019422, RCV000799304
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>De Mattia et al. (2004) described 2 families with autosomal recessive nephrogenic diabetes insipidus (NDI2; 125800) in which affected individuals were compound heterozygous for a 785C-T transition in the AQP2 gene, resulting in a pro262-to-leu (P262L) substitution in the C-terminal tail, and either a 568G-A transition in the AQP2 gene, resulting in an ala190-to-thr (A190T; 107777.0019) substitution, or an R187C (107777.0001) substitution, respectively. Upon expression in oocytes, P262L AQP2 protein properly folded and was functional in contrast to the R187C and A190T proteins. In polarized epithelial cells, P262L protein was retained in intracellular vesicles and did not localize to the ER. Upon coexpression with wildtype AQP2, P262L protein interacted with wildtype AQP2, and the resulting heterotetramer properly localized to the apical membrane. De Mattia et al. (2004) concluded that P262L would act as a mutant in autosomal dominant NDI, except that its missorting is overruled by apical sorting of wildtype AQP2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
AQP2, ALA190THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894341,
|
|
|
|
|
|
|
|
ClinVar: RCV000019423, RCV004782019
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ala190-to-thr (A190T) mutation in the AQP2 gene that was found in compound heterozygous state in affected individuals from 2 families with nephrogenic diabetes insipidus (NDI2; 125800) by De Mattia et al. (2004), see 107777.0018. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bouley, R., Breton, S., Sun, T., McLaughlin, M., Nsumu, N. N., Lin, H. Y., Ausiello, D. A., Brown, D.
|
|
<strong>Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells.</strong>
|
|
J. Clin. Invest. 106: 1115-1126, 2000.
|
|
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|
|
[PubMed: 11067864]
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|
|
[Full Text: https://doi.org/10.1172/JCI9594]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Canfield, M. C., Tamarappoo, B. K., Moses, A. M., Verkman, A. S., Holtzman, E. J.
|
|
<strong>Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.</strong>
|
|
Hum. Molec. Genet. 6: 1865-1871, 1997.
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|
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|
|
[PubMed: 9302264]
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|
|
[Full Text: https://doi.org/10.1093/hmg/6.11.1865]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Carroll, P., Al-Mojalli, H., Al-Abbad, A., Al-Hassoun, I., Al-Hamed, M., Al-Amr, R., Butt, A. I., Meyer, B. F.
|
|
<strong>Novel mutations underlying nephrogenic diabetes insipidus in Arab families.</strong>
|
|
Genet. Med. 8: 443-447, 2006.
|
|
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|
|
[PubMed: 16845277]
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|
[Full Text: https://doi.org/10.1097/01.gim.0000223554.46981.7a]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
de Mattia, F., Savelkoul, P. J. M., Bichet, D. G., Kamsteeg, E.-J., Konings, I. B. M., Marr, N., Arthus, M.-F., Lonergan, M., van Os, C. H., van der Sluijs, P., Robertson, G., Deen, P. M. T.
|
|
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