3841 lines
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Entry
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- *605555 - ARYL HYDROCARBON RECEPTOR-INTERACTING PROTEIN; AIP
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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">*605555</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/605555">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimFloatingLinksMenu">
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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 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=ENSG00000110711;t=ENST00000279146" 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=9049" 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=605555" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000110711;t=ENST00000279146" 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_001302959,NM_001302960,NM_003977" 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_003977" 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=605555" 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=10408&isoform_id=10408_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/AIP" 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/1765936,1916069,85397342,85397684,115253029,118084547,118084550,118084552,118084558,119595043,126513803,126513805,126513807,126513809,126513811,126513813,146639447,146762158,146762160,146762162,147743329,157061055,157061057,157061059,157061061,157061063,157061065,157272079,162145738,167832599,209167930,224177836,224177838,256750554,257071823,257071825,261036327,261036329,261036331,261036333,294960122,313671968,363818652,729042247,729042249,729042251,2203400776,2462528638" 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/O00170" 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=9049" 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=ENSG00000110711;t=ENST00000279146" 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=AIP" 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=AIP" 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+9049" 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/AIP" 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:9049" 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/9049" 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=chr11&hgg_gene=ENST00000279146.8&hgg_start=67483026&hgg_end=67491103&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/aip" 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=605555[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=605555[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000110711" 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=AIP" 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=AIP" 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=AIP" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=AIP&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/PA24652" 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:358" 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/FBgn0030345.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:109622" 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/AIP#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:109622" 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/9049/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://omia.org/OMIA000008/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=9049" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00016966;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-6735" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:9049" 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=AIP&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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605555
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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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ARYL HYDROCARBON RECEPTOR-INTERACTING PROTEIN; AIP
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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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HEPATITIS B VIRUS X-ASSOCIATED PROTEIN 2; XAP2<br />
|
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ARA9
|
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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=AIP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AIP</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/11/667?start=-3&limit=10&highlight=667">11q13.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:67483026-67491103&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'})">11:67,483,026-67,491,103</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<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>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
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</th>
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
|
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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>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/667?start=-3&limit=10&highlight=667">
|
|
11q13.2
|
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</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
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<span class="mim-font">
|
|
Pituitary adenoma 1, multiple types
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/102200"> 102200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Pituitary adenoma predisposition
|
|
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/102200"> 102200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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</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">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/605555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605555" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
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<p>The aryl hydrocarbon receptor (AHR; <a href="/entry/600253">600253</a>) is found in a multiprotein complex that includes the 90-kD heat shock protein (HSP90; see <a href="/entry/140571">140571</a>). The AHR is a ligand-activated transcription factor that is a member of the basic helix-loop-helix PAS superfamily. In response to ligand binding in the cytosol, the AHR-HSP90 complex translocates to the nucleus where the molecular chaperone HSP90 dissociates and the activated AHR heterodimerizes with ARNT (<a href="/entry/126110">126110</a>). The resulting complex attains binding specificity for its cognate enhancer elements to regulate transcription of a variety of xenobiotic metabolizing enzymes.</p><p>The AHR-interacting protein (AIP) was originally cloned and designated XAP2 by <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> who used a yeast 2-hybrid system to identify proteins that interact with the hepatitis B virus (HBV) X protein. By use of a yeast 2-hybrid assay to detect proteins that interact with AHR in a ligand-dependent manner, <a href="#3" class="mim-tip-reference" title="Carver, L. A., Bradfield, C. A. <strong>Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.</strong> J. Biol. Chem. 272: 11452-11456, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9111057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9111057</a>] [<a href="https://doi.org/10.1074/jbc.272.17.11452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9111057">Carver and Bradfield (1997)</a> demonstrated interaction of AIP with AHR. They cloned an AIP cDNA, which they called ARA9, from a B-lymphocyte cDNA library. AIP encodes a deduced 330-amino acid protein with a molecular mass of approximately 37 kD. It contains regions of homology to the FK506-binding proteins FKBP4 (<a href="/entry/600611">600611</a>) and FKBP1A (<a href="/entry/186945">186945</a>). The predicted protein contains 3 C-terminal consensus tetratricopeptide repeat (TPR) domains similar to the TPR domains found in FKBP4 that may mediate protein-protein interactions. AIP was also identified by <a href="#13" class="mim-tip-reference" title="Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H. <strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong> Molec. Cell. Biol. 18: 978-988, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9447995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9447995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9447995[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/10.1128/MCB.18.2.978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9447995">Meyer et al. (1998)</a>, who purified the AIP protein from the AHR cytosolic complex. <a href="#13" class="mim-tip-reference" title="Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H. <strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong> Molec. Cell. Biol. 18: 978-988, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9447995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9447995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9447995[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/10.1128/MCB.18.2.978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9447995">Meyer et al. (1998)</a> cloned simian AIP cDNA from a COS-1 cDNA library and found that it shares 98% amino acid sequence identity with human AIP. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9447995+9111057+8972861" 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="#10" class="mim-tip-reference" title="Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium. <strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong> Hum. Mutat. 31: 950-960, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20506337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20506337</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20506337[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20506337">Igreja et al. (2010)</a> stated that the AIP gene contains 6 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20506337" 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>Using somatic cell hybrid analysis and FISH, <a href="#4" class="mim-tip-reference" title="Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. <strong>Characterization of the Ah receptor-associated protein, ARA9.</strong> J. Biol. Chem. 273: 33580-33587, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>] [<a href="https://doi.org/10.1074/jbc.273.50.33580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837941">Carver et al. (1998)</a> mapped the AIP gene to chromosome 11q13.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837941" 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>Using Northern blot analysis, <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> detected a 1.25-kb AIP transcript in all 16 adult tissues tested with the exception of the liver. Expression was also detected in 3 cell lines, including cervical carcinoma, hepatocellular carcinoma, and choriocarcinoma cells. The lack of AIP expression in the liver led <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> to hypothesize that this may partially allow for the X protein to contribute to the hepatotropism of HBV. Using Northern blot analysis, <a href="#3" class="mim-tip-reference" title="Carver, L. A., Bradfield, C. A. <strong>Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.</strong> J. Biol. Chem. 272: 11452-11456, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9111057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9111057</a>] [<a href="https://doi.org/10.1074/jbc.272.17.11452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9111057">Carver and Bradfield (1997)</a> also detected expression of AIP in 15 human tissues examined, with highest levels of expression in heart, placenta, and skeletal muscle. <a href="#13" class="mim-tip-reference" title="Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H. <strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong> Molec. Cell. Biol. 18: 978-988, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9447995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9447995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9447995[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/10.1128/MCB.18.2.978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9447995">Meyer et al. (1998)</a> detected Aip expression in 11 mouse tissues examined by Northern blot analysis and RT-PCR. Using in situ hybridization in mouse embryos as early as embryonic day 9.5, <a href="#4" class="mim-tip-reference" title="Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. <strong>Characterization of the Ah receptor-associated protein, ARA9.</strong> J. Biol. Chem. 273: 33580-33587, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>] [<a href="https://doi.org/10.1074/jbc.273.50.33580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837941">Carver et al. (1998)</a> detected Aip expression that was widespread and highest in the neuroepithelium, trigeminal ganglion, branchial arches, hepatic primordia, and the primitive gut. The expression remained widespread at embryonic day 13.5, with highest levels in the derivatives of the branchial arches, and expression was seen in adult lymphoid tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9447995+9837941+9111057+8972861" 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 indirect immunofluorescence, <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> localized both the HBV X protein and AIP to the cytoplasm in cultured HeLa cells. Subcellular fractionation confirmed the localization of AIP to the cytoplasmic fraction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8972861" 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 a GST fusion protein, <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> demonstrated that AIP binds to the HBV X protein. Using a series of X protein deletion mutants in a 2-hybrid system, they identified a 14-amino acid region (amino acids 13-26) important for binding AIP. This N-terminal region of the X protein was highly conserved among mammalian hepadnaviruses. Using cotransfection experiments, <a href="#11" class="mim-tip-reference" title="Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E. <strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong> Nucleic Acids Res. 24: 4741-4750, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>] [<a href="https://doi.org/10.1093/nar/24.23.4741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8972861">Kuzhandaivelu et al. (1996)</a> showed that AIP is a specific cellular inhibitor of the X protein but not other viral transactivators. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8972861" 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="Carver, L. A., Bradfield, C. A. <strong>Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.</strong> J. Biol. Chem. 272: 11452-11456, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9111057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9111057</a>] [<a href="https://doi.org/10.1074/jbc.272.17.11452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9111057">Carver and Bradfield (1997)</a> demonstrated that the interaction between AIP and AHR is enhanced in the presence of the ligand beta-naphthoflavone. Using a yeast expression system, <a href="#4" class="mim-tip-reference" title="Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. <strong>Characterization of the Ah receptor-associated protein, ARA9.</strong> J. Biol. Chem. 273: 33580-33587, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>] [<a href="https://doi.org/10.1074/jbc.273.50.33580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837941">Carver et al. (1998)</a> demonstrated that AIP is able to enhance the ligand responsiveness of AHR. Coimmunoprecipitation experiments confirmed the interaction of AIP and AHR and suggested that AIP is present in AHR-HSP90 complexes. However, <a href="#13" class="mim-tip-reference" title="Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H. <strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong> Molec. Cell. Biol. 18: 978-988, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9447995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9447995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9447995[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/10.1128/MCB.18.2.978" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9447995">Meyer et al. (1998)</a> demonstrated that AIP is not required for AHR-HSP90 complex formation in vitro. They also found that AIP does not directly interact with HSP90, suggesting that AIP becomes associated with the complex only in the presence of AHR. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9447995+9837941+9111057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. <strong>Characterization of the Ah receptor-associated protein, ARA9.</strong> J. Biol. Chem. 273: 33580-33587, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>] [<a href="https://doi.org/10.1074/jbc.273.50.33580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837941">Carver et al. (1998)</a> attempted to define the domains required to form the AIP-HSP90-AHR complex using deletion analyses of both AIP and AHR. They demonstrated that the repressor domain of AHR, previously shown to contain domains required for HSP90 and ligand binding, is also required for interactions with AIP. The authors showed that the C-terminal TRP domains of AIP are necessary and sufficient for interactions with HSP90 and AHR and that AIP specifically associates with AHR-HSP90 complexes, but not with GR-HSP90 complexes. Also, AIP shows greater affinity for AHR-HSP90 complexes than FKBP4. Despite homology to FKBP4 and FKBP1A, <a href="#4" class="mim-tip-reference" title="Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. <strong>Characterization of the Ah receptor-associated protein, ARA9.</strong> J. Biol. Chem. 273: 33580-33587, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>] [<a href="https://doi.org/10.1074/jbc.273.50.33580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837941">Carver et al. (1998)</a> were unable to detect AIP binding to FK506. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Leontiou, C. A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H. S., Igreja, S. C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H. C., and 23 others. <strong>The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.</strong> J. Clin. Endocr. Metab. 93: 2390-2401, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381572</a>] [<a href="https://doi.org/10.1210/jc.2007-2611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381572">Leontiou et al. (2008)</a> found that overexpression of wildtype AIP in human fibroblast and pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. Their functional evaluation of AIP mutations was consistent with a tumor suppressor role for AIP and its involvement in familial acromegaly. <a href="#12" class="mim-tip-reference" title="Leontiou, C. A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H. S., Igreja, S. C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H. C., and 23 others. <strong>The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.</strong> J. Clin. Endocr. Metab. 93: 2390-2401, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381572</a>] [<a href="https://doi.org/10.1210/jc.2007-2611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381572">Leontiou et al. (2008)</a> concluded that the abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas (in cytoplasm rather than secretory vesicles) indicated deranged regulation of this protein during tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18381572" 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="#14" class="mim-tip-reference" title="Schernthaner-Reiter, M. H., Trivellin, G., Stratakis, C. A. <strong>Interaction of AIP with protein kinase A (cAMP-dependent protein kinase).</strong> Hum. Molec. Genet. 27: 2604-2613, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29726992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29726992</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29726992[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/10.1093/hmg/ddy166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29726992">Schernthaner-Reiter et al. (2018)</a> found that endogenous Aip physically interacted and colocalized with the protein kinase A (PKA) subunits R1-alpha (PRKAR1A; <a href="/entry/188830">188830</a>) and C-alpha (PRKACA; <a href="/entry/601639">601639</a>) in the cytoplasm of rat mammosomatotropinoma cell line GH3. Fractionation analysis showed that all 3 proteins localized to cytoplasm and membranes of GH3 cells. Aip interacted with R1-alpha and C-alpha separately and in a 3-protein complex. Aip overexpression reduced PKA activity in GH3 cells. C-alpha overexpression stabilized both Aip and R1-alpha protein levels independent of PKA activity. Aip protein level was regulated by translation and degradation via the ubiquitin/proteasome pathway. Aip knockdown modestly increased PKA activity in GH3 cells. Further analysis revealed that Aip functionally interacted with PDE-dependent PKA pathway activity via Pde4 (<a href="/entry/600126">600126</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29726992" 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 affected individuals from a large Finnish kindred with pituitary adenoma predisposition (PAP; see <a href="/entry/102200">102200</a>), <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> identified a truncating mutation in the AIP gene (Q14X; <a href="#0001">605555.0001</a>). Five individuals had prolactinomas, 4 had somatotropinomas, and 2 had a mixed tumor comprising both cells. The Q14X mutation was also identified in 6 of 45 Finnish patients with acromegaly from a population-based cohort. In 2 Italian sibs with somatotropinomas, <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> identified a different truncating mutation (R304X; <a href="#0003">605555.0003</a>) in the AIP gene. <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> postulated that the phenotype represents a hereditary predisposition to pituitary adenomas with very low penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16728643" 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 9 of 460 patients from Europe and the U.S. with pituitary adenomas, <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> identified 9 different mutations in the AIP gene (see, e.g., <a href="#0004">605555.0004</a>-<a href="#0006">605555.0006</a>; <a href="#0008">605555.0008</a>). Eight patients had growth hormone-secreting adenomas and 1 had Cushing disease due to an ACTH-secreting adenoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" 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="Daly, A. F., Vanbellinghen, J.-F., Khoo, S. K., Jaffrain-Rea, M.-L., Naves, L. A., Guitelman, M. A., Murat, A., Emy, P., Gimenez-Roqueplo, A.-P., Tamburrano, G., Raverot, G., Barlier, A., and 32 others. <strong>Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.</strong> J. Clin. Endocr. Metab. 92: 1891-1896, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17244780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17244780</a>] [<a href="https://doi.org/10.1210/jc.2006-2513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17244780">Daly et al. (2007)</a> studied the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA; see <a href="/entry/102200">102200</a>) from 9 different countries. Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 AIP mutations; 9 of the mutations were novel. Tumors were significantly larger (p = 0.0005) and diagnosed at a younger age (p = 0.0006) in AIP mutation-positive versus mutation-negative subjects. Although somatotropinomas predominated among FIPA families with AIP mutations, mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also found. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17244780" 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="Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium. <strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong> Hum. Mutat. 31: 950-960, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20506337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20506337</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20506337[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20506337">Igreja et al. (2010)</a> identified AIP mutations in 11 of 38 FIPA families, including 3 with large deletions. The authors reviewed the clinical characteristics of these 38 families and 26 previously reported families (<a href="#12" class="mim-tip-reference" title="Leontiou, C. A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H. S., Igreja, S. C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H. C., and 23 others. <strong>The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.</strong> J. Clin. Endocr. Metab. 93: 2390-2401, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381572</a>] [<a href="https://doi.org/10.1210/jc.2007-2611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381572">Leontiou et al., 2008</a>), confirming that patients with AIP mutations had a lower mean age at diagnosis. <a href="#10" class="mim-tip-reference" title="Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium. <strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong> Hum. Mutat. 31: 950-960, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20506337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20506337</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20506337[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20506337">Igreja et al. (2010)</a> analyzed the various types of mutations that had been found in the AIP gene, and demonstrated that a promoter mutation showed reduced in vitro activity corresponding to lower expression in patient samples and that stimulation of the protein kinase-A (see <a href="/entry/601639">601639</a>) pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing, resulting in truncated protein or reduced AIP expression. A 2-hybrid assay of protein-protein interactions of the 9 missense variants discovered to that time in the AIP gene showed variable disruption of AIP-phosphodiesterase-4A5 binding. <a href="#10" class="mim-tip-reference" title="Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium. <strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong> Hum. Mutat. 31: 950-960, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20506337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20506337</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20506337[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21292" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20506337">Igreja et al. (2010)</a> noted that overall, AIP mutations were implicated in 20 (31%) of the 64 families in their FIPA cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20506337+18381572" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Dal, J., Nielsen, E. H., Klose, M., Feldt-Rasmussen, U., Andersen, M., Vang, S., Korbonits, M., Jorgensen, J. O. L. <strong>Phenotypic and genotypic features of a large kindred with a germline AIP variant.</strong> Clin. Endocr. 93: 146-153, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32324286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32324286</a>] [<a href="https://doi.org/10.1111/cen.14207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32324286">Dal et al. (2020)</a> identified 31 individuals with heterozygosity for the R304Q (<a href="#0008">605555.0008</a>) mutation in the AIP gene in a large Danish kindred comprising 52 family members spanning 5 generations. Based on 2 cases of somatotropinomas among the mutation carriers, disease penetrance was 6%. In this cohort, there were 2 other individuals with acromegalic features, one of whom was heterozygous for R304Q. This led <a href="#6" class="mim-tip-reference" title="Dal, J., Nielsen, E. H., Klose, M., Feldt-Rasmussen, U., Andersen, M., Vang, S., Korbonits, M., Jorgensen, J. O. L. <strong>Phenotypic and genotypic features of a large kindred with a germline AIP variant.</strong> Clin. Endocr. 93: 146-153, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32324286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32324286</a>] [<a href="https://doi.org/10.1111/cen.14207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32324286">Dal et al. (2020)</a> to perform whole-exome sequencing on 3 parent-child trios from within this kindred to look for cosegregating potential modifier mutations. They identified variants of interest in 2 genes, PDE11A (<a href="/entry/604961">604961</a>; c.893A-G, N298S) and ALG14 (<a href="/entry/612866">612866</a>; c.113G-T, p.S38I); the variants were reported in gnomAD with frequencies of 0.11% and 0.37% in non-Finnish Europeans, respectively. The clinical implications of the PDE11A and ALG14 candidate mutations were unknown. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32324286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Reclassified Variants</em></strong></p><p>
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The R304Q variant in the AIP gene (<a href="#0008">605555.0008</a>) that was identified in a patient with an ACTH-secreting pituitary adenoma by <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> has been reclassified as a variant of unknown significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>9 Selected Examples</a>):</strong>
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<a href="/allelicVariants/605555" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605555[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 PITUITARY ADENOMA PREDISPOSITION</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> rs104894194 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894194;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/rs104894194?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=rs104894194" 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=rs104894194" 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=RCV000005163 OR RCV000508640 OR RCV001021869 OR RCV003555921" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005163, RCV000508640, RCV001021869, RCV003555921" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005163...</a>
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<p>In affected individuals from a large Finnish kindred with pituitary adenoma predisposition (PAP; see <a href="/entry/102200">102200</a>), <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> identified a gln14-to-ter (Q14X) substitution in exon 1 of the AIP gene. Five individuals had prolactinomas, 4 had somatotropinomas and 2 had a mixed tumor comprising both cells. The Q14X mutation was also identified in 6 of 45 Finnish patients with acromegaly (PITA1; <a href="/entry/102200">102200</a>) from a population-based cohort. Loss of heterozygosity at the AIP locus was observed in all 8 tumor tissues studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16728643" 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 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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">rs267606555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606555;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=rs267606555" 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=rs267606555" 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=RCV000005165" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005165" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005165</a>
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<p>In a Finnish patient with acromegaly and pituitary adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> identified a G-to-A substitution in intron 3 of the AIP gene, affecting the splice acceptor site of exon 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16728643" 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="0003" class="mim-anchor"></a>
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<strong>.0003 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</strong>
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AIP, ARG304TER
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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> rs104894195 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894195;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/rs104894195?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=rs104894195" 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=rs104894195" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005166 OR RCV001018873 OR RCV001213277" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005166, RCV001018873, RCV001213277" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005166...</a>
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<p>In 2 Italian sibs with GH-secreting pituitary adenomas (PITA1; <a href="/entry/102200">102200</a>), <a href="#16" class="mim-tip-reference" title="Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A. <strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong> Science 312: 1228-1230, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>] [<a href="https://doi.org/10.1126/science.1126100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16728643">Vierimaa et al. (2006)</a> identified an arg304-to-stop (R304X) substitution at codon 304 in the AIP gene. This mutation was not found in 203 Caucasian controls from the U.K. or CEPH or 52 local blood donors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16728643" 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="Daly, A. F., Vanbellinghen, J.-F., Khoo, S. K., Jaffrain-Rea, M.-L., Naves, L. A., Guitelman, M. A., Murat, A., Emy, P., Gimenez-Roqueplo, A.-P., Tamburrano, G., Raverot, G., Barlier, A., and 32 others. <strong>Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.</strong> J. Clin. Endocr. Metab. 92: 1891-1896, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17244780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17244780</a>] [<a href="https://doi.org/10.1210/jc.2006-2513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17244780">Daly et al. (2007)</a> identified the R304X mutation in 3 affected members of another Italian family with GH-secreting pituitary adenomas and acromegaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17244780" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Chahal, H. S., Stals, K., Unterlander, M., Balding, D. J., Thomas, M. G., Kumar, A. V., Besser, G. M., Atkinson, A. B., Morrison, P. J., Howlett, T. A., Levy, M. J., Orme, S. M., Akker, S. A., Abel, R. L., Grossman, A. B., Burger, J., Ellard, S., Korbonits, M. <strong>AIP mutation in pituitary adenomas in the 18th century and today.</strong> New Eng. J. Med. 364: 43-50, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21208107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21208107</a>] [<a href="https://doi.org/10.1056/NEJMoa1008020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21208107">Chahal et al. (2011)</a> identified the same nonsense mutation in DNA extracted from teeth of an Irish patient who lived from 1761 to 1783 (Charles Byrne, 'The Irish Giant'; <a href="#2" class="mim-tip-reference" title="Bergland, Richard M. <strong>New information concerning the Irish Giant.</strong> J. Neurosurg. 23: 265-269, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5320367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5320367</a>] [<a href="https://doi.org/10.3171/jns.1965.23.3.0265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5320367">Bergland, 1965</a>), whose skull had been noted by Harvey Cushing to possess an enlarged pituitary fossa. Four contemporary northern Irish families who presented with gigantism, acromegaly, or prolactinoma had the same mutation and haplotype associated with the mutated gene. Using coalescent theory, <a href="#5" class="mim-tip-reference" title="Chahal, H. S., Stals, K., Unterlander, M., Balding, D. J., Thomas, M. G., Kumar, A. V., Besser, G. M., Atkinson, A. B., Morrison, P. J., Howlett, T. A., Levy, M. J., Orme, S. M., Akker, S. A., Abel, R. L., Grossman, A. B., Burger, J., Ellard, S., Korbonits, M. <strong>AIP mutation in pituitary adenomas in the 18th century and today.</strong> New Eng. J. Med. 364: 43-50, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21208107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21208107</a>] [<a href="https://doi.org/10.1056/NEJMoa1008020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21208107">Chahal et al. (2011)</a> inferred that these persons share a common ancestor who lived about 57 to 66 generations earlier. In the 4 families, <a href="#5" class="mim-tip-reference" title="Chahal, H. S., Stals, K., Unterlander, M., Balding, D. J., Thomas, M. G., Kumar, A. V., Besser, G. M., Atkinson, A. B., Morrison, P. J., Howlett, T. A., Levy, M. J., Orme, S. M., Akker, S. A., Abel, R. L., Grossman, A. B., Burger, J., Ellard, S., Korbonits, M. <strong>AIP mutation in pituitary adenomas in the 18th century and today.</strong> New Eng. J. Med. 364: 43-50, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21208107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21208107</a>] [<a href="https://doi.org/10.1056/NEJMoa1008020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21208107">Chahal et al. (2011)</a> identified 51 carriers of the mutation but only 14 affected subjects. The level of penetrance was difficult to establish since information on genetic and clinical data were incomplete. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5320367+21208107" 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="0004" class="mim-anchor"></a>
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<strong>.0004 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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">rs267606567 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606567;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=rs267606567" 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=rs267606567" 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=RCV000005167" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005167" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005167</a>
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<p>In a 20-year-old German man with acromegaly secondary to a pituitary adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> identified a heterozygous 6-bp deletion (66delAGGAGA) in exon 1 of the AIP gene. Tumor tissue showed loss of the normal AIP allele. The patient had a family history of acromegaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" 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 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</strong>
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AIP, 1-BP INS, 824A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606580 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606580;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=rs267606580" 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=rs267606580" 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=RCV000005168" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005168" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005168</a>
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<p>In an 8-year-old boy with a GH-secreting pituitary adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> identified a heterozygous 1-bp insertion (824insA) in exon 6 of the AIP gene. Tumor tissue showed loss of the normal AIP allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<strong>.0006 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</strong>
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AIP, 1-BP DEL, 542T
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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> rs267606559 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606559;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/rs267606559?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=rs267606559" 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=rs267606559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005169" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005169" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005169</a>
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<p>In an 18-year-old man from Spain with acromegaly secondary to a pituitary adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> identified a heterozygous 1-bp deletion (542delT) in exon 4 of the AIP gene. He had a family history of acromegaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" 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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<h4>
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<span class="mim-font">
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<strong>.0007 PITUITARY ADENOMA PREDISPOSITION</strong>
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AIP, TYR268TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908356 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908356;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=rs121908356" 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=rs121908356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005170 OR RCV000034106 OR RCV003555922" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005170, RCV000034106, RCV003555922" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005170...</a>
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<p>In 4 affected members of a Brazilian family with pituitary tumor predisposition (PAP; see <a href="/entry/102200">102200</a>), <a href="#15" class="mim-tip-reference" title="Toledo, R. A., Lourenco, D. M., Jr., Liberman, B., Cunha-Neto, M. B. C., Cavalcanti, M. G., Moyses, C. B., Toledo, S. P. A., Dahia, P. L. M. <strong>Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma.</strong> J. Clin. Endocr. Metab. 92: 1934-1937, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17341560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17341560</a>] [<a href="https://doi.org/10.1210/jc.2006-2394" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17341560">Toledo et al. (2007)</a> identified heterozygosity for an 804A-C transversion in the AIP gene, resulting in a tyr268-to-ter (Y268X) substitution predicted to generate a protein lacking 2 conserved domains. The 4 affected members included 2 sibs with early-onset acromegaly, a 41-year-old sib with a nonsecreting microadenoma and no clinical features of disease, and his 3-year-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17341560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0008 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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AIP, ARG304GLN
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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> rs104894190 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894190;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/rs104894190?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=rs104894190" 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=rs104894190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005171 OR RCV000439236 OR RCV000508590 OR RCV000571906 OR RCV000735427 OR RCV000766368 OR RCV004748499" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005171, RCV000439236, RCV000508590, RCV000571906, RCV000735427, RCV000766368, RCV004748499" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005171...</a>
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<p>This variant, formerly titled PITUITARY ADENOMA 1, ACTH-SECRETING, has been reclassified based on review of the gnomAD database by <a href="#9" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 1/17/2024."None>Hamosh (2024)</a>.</p><p>In a 26-year-old Polish patient with Cushing disease due to an ACTH-secreting pituitary adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#8" class="mim-tip-reference" title="Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A. <strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong> Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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.0700004104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360484">Georgitsi et al. (2007)</a> identified a heterozygous c.911G-A transition in exon 6 of the AIP gene, resulting in an arg304-to-gln (R304Q) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360484" 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 large Danish kindred comprising 52 family members spanning 5 generations, <a href="#6" class="mim-tip-reference" title="Dal, J., Nielsen, E. H., Klose, M., Feldt-Rasmussen, U., Andersen, M., Vang, S., Korbonits, M., Jorgensen, J. O. L. <strong>Phenotypic and genotypic features of a large kindred with a germline AIP variant.</strong> Clin. Endocr. 93: 146-153, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32324286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32324286</a>] [<a href="https://doi.org/10.1111/cen.14207" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32324286">Dal et al. (2020)</a> identified 31 individuals with heterozygosity for the R304Q mutation. Based on 2 cases of somatotropinomas among the mutation carriers, the disease penetrance was 6%. Two individuals with homozygosity for R304Q were reported in the gnomAD database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32324286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 1/17/2024."None>Hamosh (2024)</a> noted that the R304Q variant was present in 437 of 278,694 alleles and in 2 homozygotes, with an allele frequency of 0.001568, in the gnomAD database (v2.1). She stated that R304Q may be a low penetrance susceptibility allele.</p>
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<strong>.0009 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</strong>
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AIP, ARG22TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908357 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908357;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=rs121908357" 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=rs121908357" 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=RCV000005172" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005172" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005172</a>
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<p>In a 24-year-old man with acromegaly due to a GH-secreting adenoma (PITA1; <a href="/entry/102200">102200</a>), <a href="#1" class="mim-tip-reference" title="Barlier, A., Vanbellinghen, J.-F., Daly, A. F., Silvy, M., Jaffrain-Rea, M.-L., Trouillas, J., Tamagno, G., Cazabat, L., Bours, V., Brue, T., Enjalbert, A., Beckers, A. <strong>Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.</strong> J. Clin. Endocr. Metab. 92: 1952-1955, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299063</a>] [<a href="https://doi.org/10.1210/jc.2006-2702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17299063">Barlier et al. (2007)</a> identified a heterozygous C-to-T transition in exon 1 of the AIP gene, resulting in an arg22-to-ter (R22X) substitution. The tumor tissue showed loss of heterozygosity at the AIP locus. The patient had an aggressive macroadenoma that was resistant to somatostatin agonist therapy. He also required radiotherapy postoperatively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17299063" 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>REFERENCES</strong>
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Barlier, A., Vanbellinghen, J.-F., Daly, A. F., Silvy, M., Jaffrain-Rea, M.-L., Trouillas, J., Tamagno, G., Cazabat, L., Bours, V., Brue, T., Enjalbert, A., Beckers, A.
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<strong>Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.</strong>
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J. Clin. Endocr. Metab. 92: 1952-1955, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17299063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17299063</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17299063" 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/jc.2006-2702" target="_blank">Full Text</a>]
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Bergland, Richard M.
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<strong>New information concerning the Irish Giant.</strong>
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J. Neurosurg. 23: 265-269, 1965.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5320367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5320367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5320367" 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/10.3171/jns.1965.23.3.0265" target="_blank">Full Text</a>]
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Carver, L. A., Bradfield, C. A.
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<strong>Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.</strong>
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J. Biol. Chem. 272: 11452-11456, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9111057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9111057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9111057" 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.272.17.11452" target="_blank">Full Text</a>]
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Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A.
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<strong>Characterization of the Ah receptor-associated protein, ARA9.</strong>
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J. Biol. Chem. 273: 33580-33587, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837941" 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.273.50.33580" target="_blank">Full Text</a>]
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Chahal, H. S., Stals, K., Unterlander, M., Balding, D. J., Thomas, M. G., Kumar, A. V., Besser, G. M., Atkinson, A. B., Morrison, P. J., Howlett, T. A., Levy, M. J., Orme, S. M., Akker, S. A., Abel, R. L., Grossman, A. B., Burger, J., Ellard, S., Korbonits, M.
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<strong>AIP mutation in pituitary adenomas in the 18th century and today.</strong>
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New Eng. J. Med. 364: 43-50, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21208107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21208107</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21208107" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMoa1008020" target="_blank">Full Text</a>]
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Dal, J., Nielsen, E. H., Klose, M., Feldt-Rasmussen, U., Andersen, M., Vang, S., Korbonits, M., Jorgensen, J. O. L.
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<strong>Phenotypic and genotypic features of a large kindred with a germline AIP variant.</strong>
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Clin. Endocr. 93: 146-153, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32324286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32324286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32324286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Daly, A. F., Vanbellinghen, J.-F., Khoo, S. K., Jaffrain-Rea, M.-L., Naves, L. A., Guitelman, M. A., Murat, A., Emy, P., Gimenez-Roqueplo, A.-P., Tamburrano, G., Raverot, G., Barlier, A., and 32 others.
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<strong>Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.</strong>
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J. Clin. Endocr. Metab. 92: 1891-1896, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17244780/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17244780</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17244780" 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/jc.2006-2513" target="_blank">Full Text</a>]
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Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A.
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<strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong>
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Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360484</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360484[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=17360484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0700004104" target="_blank">Full Text</a>]
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Hamosh, A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 1/17/2024.
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Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium.
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<strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong>
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Hum. Mutat. 31: 950-960, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20506337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20506337</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20506337[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=20506337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.21292" target="_blank">Full Text</a>]
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<a id="Kuzhandaivelu1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E.
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|
<strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong>
|
|
Nucleic Acids Res. 24: 4741-4750, 1996.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8972861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8972861</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8972861" 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/nar/24.23.4741" 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="12" class="mim-anchor"></a>
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<a id="Leontiou2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Leontiou, C. A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H. S., Igreja, S. C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H. C., and 23 others.
|
|
<strong>The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.</strong>
|
|
J. Clin. Endocr. Metab. 93: 2390-2401, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381572/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381572</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18381572" 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/jc.2007-2611" 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="13" class="mim-anchor"></a>
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<a id="Meyer1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H.
|
|
<strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong>
|
|
Molec. Cell. Biol. 18: 978-988, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9447995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9447995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9447995[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=9447995" 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/10.1128/MCB.18.2.978" 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="14" class="mim-anchor"></a>
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<a id="Schernthaner-Reiter2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Schernthaner-Reiter, M. H., Trivellin, G., Stratakis, C. A.
|
|
<strong>Interaction of AIP with protein kinase A (cAMP-dependent protein kinase).</strong>
|
|
Hum. Molec. Genet. 27: 2604-2613, 2018.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29726992/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29726992</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29726992[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=29726992" 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/ddy166" 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="15" class="mim-anchor"></a>
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<a id="Toledo2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Toledo, R. A., Lourenco, D. M., Jr., Liberman, B., Cunha-Neto, M. B. C., Cavalcanti, M. G., Moyses, C. B., Toledo, S. P. A., Dahia, P. L. M.
|
|
<strong>Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma.</strong>
|
|
J. Clin. Endocr. Metab. 92: 1934-1937, 2007.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17341560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17341560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17341560" 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/jc.2006-2394" 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="16" class="mim-anchor"></a>
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<a id="Vierimaa2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A.
|
|
<strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong>
|
|
Science 312: 1228-1230, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16728643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16728643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16728643" 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/10.1126/science.1126100" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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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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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 01/17/2024
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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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Hilary J. Vernon - updated : 09/14/2020<br>Bao Lige - updated : 02/25/2020<br>Carol A. Bocchini - updated : 09/26/2017<br>Ada Hamosh - updated : 1/19/2011<br>Marla J. F. O'Neill - updated : 12/20/2010<br>John A. Phillips, III - updated : 1/13/2009<br>Cassandra L. Kniffin - updated : 2/19/2008<br>John A. Phillips, III - updated : 2/14/2008<br>Cassandra L. Kniffin - updated : 3/26/2007<br>Ada Hamosh - updated : 7/21/2006
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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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<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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Dawn Watkins-Chow : 1/16/2001
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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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<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 : 01/17/2024
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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 : 09/14/2020<br>mgross : 02/25/2020<br>mgross : 02/25/2020<br>carol : 09/27/2017<br>carol : 09/26/2017<br>carol : 02/26/2015<br>alopez : 2/5/2015<br>alopez : 2/5/2015<br>alopez : 2/5/2015<br>alopez : 1/25/2011<br>terry : 1/19/2011<br>alopez : 12/20/2010<br>terry : 12/20/2010<br>carol : 2/24/2010<br>alopez : 1/13/2009<br>carol : 2/28/2008<br>ckniffin : 2/19/2008<br>carol : 2/14/2008<br>carol : 2/14/2008<br>wwang : 4/12/2007<br>ckniffin : 3/26/2007<br>alopez : 7/25/2006<br>terry : 7/21/2006<br>carol : 1/17/2001
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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>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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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> 605555
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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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|
ARYL HYDROCARBON RECEPTOR-INTERACTING PROTEIN; AIP
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<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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HEPATITIS B VIRUS X-ASSOCIATED PROTEIN 2; XAP2<br />
|
|
ARA9
|
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: AIP</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: 11q13.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:67,483,026-67,491,103 </span>
|
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</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
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>
|
|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
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="2">
|
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<span class="mim-font">
|
|
11q13.2
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Pituitary adenoma 1, multiple types
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
102200
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant; Somatic mutation
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
3
|
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</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Pituitary adenoma predisposition
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
102200
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant; Somatic mutation
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>The aryl hydrocarbon receptor (AHR; 600253) is found in a multiprotein complex that includes the 90-kD heat shock protein (HSP90; see 140571). The AHR is a ligand-activated transcription factor that is a member of the basic helix-loop-helix PAS superfamily. In response to ligand binding in the cytosol, the AHR-HSP90 complex translocates to the nucleus where the molecular chaperone HSP90 dissociates and the activated AHR heterodimerizes with ARNT (126110). The resulting complex attains binding specificity for its cognate enhancer elements to regulate transcription of a variety of xenobiotic metabolizing enzymes.</p><p>The AHR-interacting protein (AIP) was originally cloned and designated XAP2 by Kuzhandaivelu et al. (1996) who used a yeast 2-hybrid system to identify proteins that interact with the hepatitis B virus (HBV) X protein. By use of a yeast 2-hybrid assay to detect proteins that interact with AHR in a ligand-dependent manner, Carver and Bradfield (1997) demonstrated interaction of AIP with AHR. They cloned an AIP cDNA, which they called ARA9, from a B-lymphocyte cDNA library. AIP encodes a deduced 330-amino acid protein with a molecular mass of approximately 37 kD. It contains regions of homology to the FK506-binding proteins FKBP4 (600611) and FKBP1A (186945). The predicted protein contains 3 C-terminal consensus tetratricopeptide repeat (TPR) domains similar to the TPR domains found in FKBP4 that may mediate protein-protein interactions. AIP was also identified by Meyer et al. (1998), who purified the AIP protein from the AHR cytosolic complex. Meyer et al. (1998) cloned simian AIP cDNA from a COS-1 cDNA library and found that it shares 98% amino acid sequence identity with human AIP. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
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|
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|
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<span class="mim-text-font">
|
|
<p>Igreja et al. (2010) stated that the AIP gene contains 6 exons. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<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>Using somatic cell hybrid analysis and FISH, Carver et al. (1998) mapped the AIP gene to chromosome 11q13.3. </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>Using Northern blot analysis, Kuzhandaivelu et al. (1996) detected a 1.25-kb AIP transcript in all 16 adult tissues tested with the exception of the liver. Expression was also detected in 3 cell lines, including cervical carcinoma, hepatocellular carcinoma, and choriocarcinoma cells. The lack of AIP expression in the liver led Kuzhandaivelu et al. (1996) to hypothesize that this may partially allow for the X protein to contribute to the hepatotropism of HBV. Using Northern blot analysis, Carver and Bradfield (1997) also detected expression of AIP in 15 human tissues examined, with highest levels of expression in heart, placenta, and skeletal muscle. Meyer et al. (1998) detected Aip expression in 11 mouse tissues examined by Northern blot analysis and RT-PCR. Using in situ hybridization in mouse embryos as early as embryonic day 9.5, Carver et al. (1998) detected Aip expression that was widespread and highest in the neuroepithelium, trigeminal ganglion, branchial arches, hepatic primordia, and the primitive gut. The expression remained widespread at embryonic day 13.5, with highest levels in the derivatives of the branchial arches, and expression was seen in adult lymphoid tissues. </p><p>Using indirect immunofluorescence, Kuzhandaivelu et al. (1996) localized both the HBV X protein and AIP to the cytoplasm in cultured HeLa cells. Subcellular fractionation confirmed the localization of AIP to the cytoplasmic fraction. </p><p>Using a GST fusion protein, Kuzhandaivelu et al. (1996) demonstrated that AIP binds to the HBV X protein. Using a series of X protein deletion mutants in a 2-hybrid system, they identified a 14-amino acid region (amino acids 13-26) important for binding AIP. This N-terminal region of the X protein was highly conserved among mammalian hepadnaviruses. Using cotransfection experiments, Kuzhandaivelu et al. (1996) showed that AIP is a specific cellular inhibitor of the X protein but not other viral transactivators. </p><p>Carver and Bradfield (1997) demonstrated that the interaction between AIP and AHR is enhanced in the presence of the ligand beta-naphthoflavone. Using a yeast expression system, Carver et al. (1998) demonstrated that AIP is able to enhance the ligand responsiveness of AHR. Coimmunoprecipitation experiments confirmed the interaction of AIP and AHR and suggested that AIP is present in AHR-HSP90 complexes. However, Meyer et al. (1998) demonstrated that AIP is not required for AHR-HSP90 complex formation in vitro. They also found that AIP does not directly interact with HSP90, suggesting that AIP becomes associated with the complex only in the presence of AHR. </p><p>Carver et al. (1998) attempted to define the domains required to form the AIP-HSP90-AHR complex using deletion analyses of both AIP and AHR. They demonstrated that the repressor domain of AHR, previously shown to contain domains required for HSP90 and ligand binding, is also required for interactions with AIP. The authors showed that the C-terminal TRP domains of AIP are necessary and sufficient for interactions with HSP90 and AHR and that AIP specifically associates with AHR-HSP90 complexes, but not with GR-HSP90 complexes. Also, AIP shows greater affinity for AHR-HSP90 complexes than FKBP4. Despite homology to FKBP4 and FKBP1A, Carver et al. (1998) were unable to detect AIP binding to FK506. </p><p>Leontiou et al. (2008) found that overexpression of wildtype AIP in human fibroblast and pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. Their functional evaluation of AIP mutations was consistent with a tumor suppressor role for AIP and its involvement in familial acromegaly. Leontiou et al. (2008) concluded that the abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas (in cytoplasm rather than secretory vesicles) indicated deranged regulation of this protein during tumorigenesis. </p><p>Schernthaner-Reiter et al. (2018) found that endogenous Aip physically interacted and colocalized with the protein kinase A (PKA) subunits R1-alpha (PRKAR1A; 188830) and C-alpha (PRKACA; 601639) in the cytoplasm of rat mammosomatotropinoma cell line GH3. Fractionation analysis showed that all 3 proteins localized to cytoplasm and membranes of GH3 cells. Aip interacted with R1-alpha and C-alpha separately and in a 3-protein complex. Aip overexpression reduced PKA activity in GH3 cells. C-alpha overexpression stabilized both Aip and R1-alpha protein levels independent of PKA activity. Aip protein level was regulated by translation and degradation via the ubiquitin/proteasome pathway. Aip knockdown modestly increased PKA activity in GH3 cells. Further analysis revealed that Aip functionally interacted with PDE-dependent PKA pathway activity via Pde4 (600126). </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 affected individuals from a large Finnish kindred with pituitary adenoma predisposition (PAP; see 102200), Vierimaa et al. (2006) identified a truncating mutation in the AIP gene (Q14X; 605555.0001). Five individuals had prolactinomas, 4 had somatotropinomas, and 2 had a mixed tumor comprising both cells. The Q14X mutation was also identified in 6 of 45 Finnish patients with acromegaly from a population-based cohort. In 2 Italian sibs with somatotropinomas, Vierimaa et al. (2006) identified a different truncating mutation (R304X; 605555.0003) in the AIP gene. Vierimaa et al. (2006) postulated that the phenotype represents a hereditary predisposition to pituitary adenomas with very low penetrance. </p><p>In 9 of 460 patients from Europe and the U.S. with pituitary adenomas, Georgitsi et al. (2007) identified 9 different mutations in the AIP gene (see, e.g., 605555.0004-605555.0006; 605555.0008). Eight patients had growth hormone-secreting adenomas and 1 had Cushing disease due to an ACTH-secreting adenoma. </p><p>Daly et al. (2007) studied the frequency of AIP gene mutations in a large cohort of patients with familial isolated pituitary adenoma (FIPA; see 102200) from 9 different countries. Seventy-three FIPA families were identified, with 156 patients with pituitary adenomas; the FIPA cohort was evenly divided between families with homogeneous and heterogeneous tumor expression. Eleven FIPA families had 10 AIP mutations; 9 of the mutations were novel. Tumors were significantly larger (p = 0.0005) and diagnosed at a younger age (p = 0.0006) in AIP mutation-positive versus mutation-negative subjects. Although somatotropinomas predominated among FIPA families with AIP mutations, mixed GH/prolactin-secreting tumors, prolactinomas, and nonsecreting adenomas were also found. Approximately 85% of the FIPA cohort and 50% of those with familial somatotropinomas were negative for AIP mutations. </p><p>Igreja et al. (2010) identified AIP mutations in 11 of 38 FIPA families, including 3 with large deletions. The authors reviewed the clinical characteristics of these 38 families and 26 previously reported families (Leontiou et al., 2008), confirming that patients with AIP mutations had a lower mean age at diagnosis. Igreja et al. (2010) analyzed the various types of mutations that had been found in the AIP gene, and demonstrated that a promoter mutation showed reduced in vitro activity corresponding to lower expression in patient samples and that stimulation of the protein kinase-A (see 601639) pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing, resulting in truncated protein or reduced AIP expression. A 2-hybrid assay of protein-protein interactions of the 9 missense variants discovered to that time in the AIP gene showed variable disruption of AIP-phosphodiesterase-4A5 binding. Igreja et al. (2010) noted that overall, AIP mutations were implicated in 20 (31%) of the 64 families in their FIPA cohort. </p><p>Dal et al. (2020) identified 31 individuals with heterozygosity for the R304Q (605555.0008) mutation in the AIP gene in a large Danish kindred comprising 52 family members spanning 5 generations. Based on 2 cases of somatotropinomas among the mutation carriers, disease penetrance was 6%. In this cohort, there were 2 other individuals with acromegalic features, one of whom was heterozygous for R304Q. This led Dal et al. (2020) to perform whole-exome sequencing on 3 parent-child trios from within this kindred to look for cosegregating potential modifier mutations. They identified variants of interest in 2 genes, PDE11A (604961; c.893A-G, N298S) and ALG14 (612866; c.113G-T, p.S38I); the variants were reported in gnomAD with frequencies of 0.11% and 0.37% in non-Finnish Europeans, respectively. The clinical implications of the PDE11A and ALG14 candidate mutations were unknown. </p><p><strong><em>Reclassified Variants</em></strong></p><p>
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The R304Q variant in the AIP gene (605555.0008) that was identified in a patient with an ACTH-secreting pituitary adenoma by Georgitsi et al. (2007) has been reclassified as a variant of unknown significance. </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>9 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 PITUITARY ADENOMA PREDISPOSITION</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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PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING, INCLUDED
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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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AIP, GLN14TER
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<br />
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SNP: rs104894194,
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gnomAD: rs104894194,
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ClinVar: RCV000005163, RCV000508640, RCV001021869, RCV003555921
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected individuals from a large Finnish kindred with pituitary adenoma predisposition (PAP; see 102200), Vierimaa et al. (2006) identified a gln14-to-ter (Q14X) substitution in exon 1 of the AIP gene. Five individuals had prolactinomas, 4 had somatotropinomas and 2 had a mixed tumor comprising both cells. The Q14X mutation was also identified in 6 of 45 Finnish patients with acromegaly (PITA1; 102200) from a population-based cohort. Loss of heterozygosity at the AIP locus was observed in all 8 tumor tissues studied. </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 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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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AIP, IVS3AS, G-A, -1
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<br />
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SNP: rs267606555,
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ClinVar: RCV000005165
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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 Finnish patient with acromegaly and pituitary adenoma (PITA1; 102200), Vierimaa et al. (2006) identified a G-to-A substitution in intron 3 of the AIP gene, affecting the splice acceptor site of exon 4. </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>.0003 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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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AIP, ARG304TER
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<br />
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SNP: rs104894195,
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gnomAD: rs104894195,
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ClinVar: RCV000005166, RCV001018873, RCV001213277
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Italian sibs with GH-secreting pituitary adenomas (PITA1; 102200), Vierimaa et al. (2006) identified an arg304-to-stop (R304X) substitution at codon 304 in the AIP gene. This mutation was not found in 203 Caucasian controls from the U.K. or CEPH or 52 local blood donors. </p><p>Daly et al. (2007) identified the R304X mutation in 3 affected members of another Italian family with GH-secreting pituitary adenomas and acromegaly. </p><p>Chahal et al. (2011) identified the same nonsense mutation in DNA extracted from teeth of an Irish patient who lived from 1761 to 1783 (Charles Byrne, 'The Irish Giant'; Bergland, 1965), whose skull had been noted by Harvey Cushing to possess an enlarged pituitary fossa. Four contemporary northern Irish families who presented with gigantism, acromegaly, or prolactinoma had the same mutation and haplotype associated with the mutated gene. Using coalescent theory, Chahal et al. (2011) inferred that these persons share a common ancestor who lived about 57 to 66 generations earlier. In the 4 families, Chahal et al. (2011) identified 51 carriers of the mutation but only 14 affected subjects. The level of penetrance was difficult to establish since information on genetic and clinical data were incomplete. </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>.0004 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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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AIP, 6-BP DEL, NT66
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<br />
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SNP: rs267606567,
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ClinVar: RCV000005167
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 20-year-old German man with acromegaly secondary to a pituitary adenoma (PITA1; 102200), Georgitsi et al. (2007) identified a heterozygous 6-bp deletion (66delAGGAGA) in exon 1 of the AIP gene. Tumor tissue showed loss of the normal AIP allele. The patient had a family history of acromegaly. </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 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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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AIP, 1-BP INS, 824A
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<br />
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SNP: rs267606580,
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ClinVar: RCV000005168
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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 an 8-year-old boy with a GH-secreting pituitary adenoma (PITA1; 102200), Georgitsi et al. (2007) identified a heterozygous 1-bp insertion (824insA) in exon 6 of the AIP gene. Tumor tissue showed loss of the normal AIP allele. </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>.0006 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</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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AIP, 1-BP DEL, 542T
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<br />
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SNP: rs267606559,
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gnomAD: rs267606559,
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ClinVar: RCV000005169
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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 an 18-year-old man from Spain with acromegaly secondary to a pituitary adenoma (PITA1; 102200), Georgitsi et al. (2007) identified a heterozygous 1-bp deletion (542delT) in exon 4 of the AIP gene. He had a family history of acromegaly. </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>.0007 PITUITARY ADENOMA PREDISPOSITION</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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AIP, TYR268TER
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<br />
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SNP: rs121908356,
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ClinVar: RCV000005170, RCV000034106, RCV003555922
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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 4 affected members of a Brazilian family with pituitary tumor predisposition (PAP; see 102200), Toledo et al. (2007) identified heterozygosity for an 804A-C transversion in the AIP gene, resulting in a tyr268-to-ter (Y268X) substitution predicted to generate a protein lacking 2 conserved domains. The 4 affected members included 2 sibs with early-onset acromegaly, a 41-year-old sib with a nonsecreting microadenoma and no clinical features of disease, and his 3-year-old son. No changes were found in 14 unaffected at-risk relatives or 92 healthy controls. </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>.0008 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</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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AIP, ARG304GLN
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<br />
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SNP: rs104894190,
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gnomAD: rs104894190,
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ClinVar: RCV000005171, RCV000439236, RCV000508590, RCV000571906, RCV000735427, RCV000766368, RCV004748499
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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>This variant, formerly titled PITUITARY ADENOMA 1, ACTH-SECRETING, has been reclassified based on review of the gnomAD database by Hamosh (2024).</p><p>In a 26-year-old Polish patient with Cushing disease due to an ACTH-secreting pituitary adenoma (PITA1; 102200), Georgitsi et al. (2007) identified a heterozygous c.911G-A transition in exon 6 of the AIP gene, resulting in an arg304-to-gln (R304Q) substitution. </p><p>In a large Danish kindred comprising 52 family members spanning 5 generations, Dal et al. (2020) identified 31 individuals with heterozygosity for the R304Q mutation. Based on 2 cases of somatotropinomas among the mutation carriers, the disease penetrance was 6%. Two individuals with homozygosity for R304Q were reported in the gnomAD database. </p><p>Hamosh (2024) noted that the R304Q variant was present in 437 of 278,694 alleles and in 2 homozygotes, with an allele frequency of 0.001568, in the gnomAD database (v2.1). She stated that R304Q may be a low penetrance susceptibility allele.</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>.0009 PITUITARY ADENOMA 1, GROWTH HORMONE-SECRETING</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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AIP, ARG22TER
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<br />
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SNP: rs121908357,
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ClinVar: RCV000005172
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<p>In a 24-year-old man with acromegaly due to a GH-secreting adenoma (PITA1; 102200), Barlier et al. (2007) identified a heterozygous C-to-T transition in exon 1 of the AIP gene, resulting in an arg22-to-ter (R22X) substitution. The tumor tissue showed loss of heterozygosity at the AIP locus. The patient had an aggressive macroadenoma that was resistant to somatostatin agonist therapy. He also required radiotherapy postoperatively. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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<p class="mim-text-font">
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Barlier, A., Vanbellinghen, J.-F., Daly, A. F., Silvy, M., Jaffrain-Rea, M.-L., Trouillas, J., Tamagno, G., Cazabat, L., Bours, V., Brue, T., Enjalbert, A., Beckers, A.
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<strong>Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.</strong>
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J. Clin. Endocr. Metab. 92: 1952-1955, 2007.
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[PubMed: 17299063]
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[Full Text: https://doi.org/10.1210/jc.2006-2702]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bergland, Richard M.
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<strong>New information concerning the Irish Giant.</strong>
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J. Neurosurg. 23: 265-269, 1965.
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[PubMed: 5320367]
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[Full Text: https://doi.org/10.3171/jns.1965.23.3.0265]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Carver, L. A., Bradfield, C. A.
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<strong>Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.</strong>
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J. Biol. Chem. 272: 11452-11456, 1997.
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[PubMed: 9111057]
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[Full Text: https://doi.org/10.1074/jbc.272.17.11452]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A.
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<strong>Characterization of the Ah receptor-associated protein, ARA9.</strong>
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J. Biol. Chem. 273: 33580-33587, 1998.
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[PubMed: 9837941]
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[Full Text: https://doi.org/10.1074/jbc.273.50.33580]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Chahal, H. S., Stals, K., Unterlander, M., Balding, D. J., Thomas, M. G., Kumar, A. V., Besser, G. M., Atkinson, A. B., Morrison, P. J., Howlett, T. A., Levy, M. J., Orme, S. M., Akker, S. A., Abel, R. L., Grossman, A. B., Burger, J., Ellard, S., Korbonits, M.
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<strong>AIP mutation in pituitary adenomas in the 18th century and today.</strong>
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New Eng. J. Med. 364: 43-50, 2011.
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[PubMed: 21208107]
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[Full Text: https://doi.org/10.1056/NEJMoa1008020]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dal, J., Nielsen, E. H., Klose, M., Feldt-Rasmussen, U., Andersen, M., Vang, S., Korbonits, M., Jorgensen, J. O. L.
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<strong>Phenotypic and genotypic features of a large kindred with a germline AIP variant.</strong>
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Clin. Endocr. 93: 146-153, 2020.
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[PubMed: 32324286]
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[Full Text: https://doi.org/10.1111/cen.14207]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Daly, A. F., Vanbellinghen, J.-F., Khoo, S. K., Jaffrain-Rea, M.-L., Naves, L. A., Guitelman, M. A., Murat, A., Emy, P., Gimenez-Roqueplo, A.-P., Tamburrano, G., Raverot, G., Barlier, A., and 32 others.
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<strong>Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families.</strong>
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J. Clin. Endocr. Metab. 92: 1891-1896, 2007.
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[PubMed: 17244780]
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[Full Text: https://doi.org/10.1210/jc.2006-2513]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Georgitsi, M., Raitila, A., Karhu, A., Tuppurainen, K., Makinen, M. J., Vierimaa, O., Paschke, R., Saeger, W., van der Luijt, R. B., Sane, T., Robledo, M., De Menis, E., Weil, R. J., Wasik, A., Zielinski, G., Lucewicz, O., Lubinski, J., Launonen, V., Vahteristo, P., Aaltonen, L. A.
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<strong>Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.</strong>
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Proc. Nat. Acad. Sci. 104: 4101-4105, 2007.
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[PubMed: 17360484]
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[Full Text: https://doi.org/10.1073/pnas.0700004104]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hamosh, A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 1/17/2024.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Igreja, S., Chahal, H. S., King, P., Bolger, G. B., Srirangalingam, U., Guasti, L., Chapple, J. P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A. V., Ellard, S., Grossman, A. B., Korbonits, M., International FIPA Consortium.
|
|
<strong>Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families.</strong>
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Hum. Mutat. 31: 950-960, 2010.
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[PubMed: 20506337]
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[Full Text: https://doi.org/10.1002/humu.21292]
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</li>
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<li>
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<p class="mim-text-font">
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Kuzhandaivelu, N., Cong, Y.-S., Inouye, C., Yang, W.-M., Seto, E.
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<strong>XAP2, a novel hepatitis B virus X-associated protein that inhibits X transactivation.</strong>
|
|
Nucleic Acids Res. 24: 4741-4750, 1996.
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[PubMed: 8972861]
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[Full Text: https://doi.org/10.1093/nar/24.23.4741]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Leontiou, C. A., Gueorguiev, M., van der Spuy, J., Quinton, R., Lolli, F., Hassan, S., Chahal, H. S., Igreja, S. C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H. C., and 23 others.
|
|
<strong>The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.</strong>
|
|
J. Clin. Endocr. Metab. 93: 2390-2401, 2008.
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[PubMed: 18381572]
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[Full Text: https://doi.org/10.1210/jc.2007-2611]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Meyer, B. K., Pray-Grant, M. G., Vanden Heuvel, J. P., Perdew, G. H.
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<strong>Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity.</strong>
|
|
Molec. Cell. Biol. 18: 978-988, 1998.
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[PubMed: 9447995]
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[Full Text: https://doi.org/10.1128/MCB.18.2.978]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Schernthaner-Reiter, M. H., Trivellin, G., Stratakis, C. A.
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<strong>Interaction of AIP with protein kinase A (cAMP-dependent protein kinase).</strong>
|
|
Hum. Molec. Genet. 27: 2604-2613, 2018.
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[PubMed: 29726992]
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[Full Text: https://doi.org/10.1093/hmg/ddy166]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Toledo, R. A., Lourenco, D. M., Jr., Liberman, B., Cunha-Neto, M. B. C., Cavalcanti, M. G., Moyses, C. B., Toledo, S. P. A., Dahia, P. L. M.
|
|
<strong>Germline mutation in the aryl hydrocarbon receptor interacting protein gene in familial somatotropinoma.</strong>
|
|
J. Clin. Endocr. Metab. 92: 1934-1937, 2007.
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[PubMed: 17341560]
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[Full Text: https://doi.org/10.1210/jc.2006-2394]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Vierimaa, O., Georgitsi, M., Lehtonen, R., Vahteristo, P., Kokko, A., Raitila, A., Tuppurainen, K., Ebeling, T. M. L., Salmela, P. I., Paschke, R., Gundogdu, S., De Menis, E., Makinen, M. J., Launonen, V., Karhu, A., Aaltonen, L. A.
|
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<strong>Pituitary adenoma predisposition caused by germline mutations in the AIP gene.</strong>
|
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Science 312: 1228-1230, 2006.
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[PubMed: 16728643]
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[Full Text: https://doi.org/10.1126/science.1126100]
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Contributors:
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Ada Hamosh - updated : 01/17/2024<br>Hilary J. Vernon - updated : 09/14/2020<br>Bao Lige - updated : 02/25/2020<br>Carol A. Bocchini - updated : 09/26/2017<br>Ada Hamosh - updated : 1/19/2011<br>Marla J. F. O'Neill - updated : 12/20/2010<br>John A. Phillips, III - updated : 1/13/2009<br>Cassandra L. Kniffin - updated : 2/19/2008<br>John A. Phillips, III - updated : 2/14/2008<br>Cassandra L. Kniffin - updated : 3/26/2007<br>Ada Hamosh - updated : 7/21/2006
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<span class="mim-text-font">
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Dawn Watkins-Chow : 1/16/2001
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carol : 01/17/2024<br>carol : 09/14/2020<br>mgross : 02/25/2020<br>mgross : 02/25/2020<br>carol : 09/27/2017<br>carol : 09/26/2017<br>carol : 02/26/2015<br>alopez : 2/5/2015<br>alopez : 2/5/2015<br>alopez : 2/5/2015<br>alopez : 1/25/2011<br>terry : 1/19/2011<br>alopez : 12/20/2010<br>terry : 12/20/2010<br>carol : 2/24/2010<br>alopez : 1/13/2009<br>carol : 2/28/2008<br>ckniffin : 2/19/2008<br>carol : 2/14/2008<br>carol : 2/14/2008<br>wwang : 4/12/2007<br>ckniffin : 3/26/2007<br>alopez : 7/25/2006<br>terry : 7/21/2006<br>carol : 1/17/2001
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