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<title>
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Entry
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- *604392 - ARYLHYDROCARBON-INTERACTING RECEPTOR PROTEIN-LIKE 1; AIPL1
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<div class="row">
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*604392</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604392">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000129221;t=ENST00000381129" 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=23746" 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=604392" 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=ENSG00000129221;t=ENST00000381129" 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_001033054,NM_001033055,NM_001285399,NM_001285400,NM_001285401,NM_001285402,NM_001285403,NM_014336" 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_014336" 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=604392" 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=05092&isoform_id=05092_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/AIPL1" 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/6716707,8248030,10436185,15082299,22001352,23503042,31873927,33337542,45720457,45720459,51997138,51997140,74272276,74272278,74272280,119610716,119610717,119610718,119610719,119610720,119610721,189069477,326205214,326205216,326205218,326205220,326205222,326205224,326205226,326205228,326205230,326205232,326205234,326205236,326205238,326205240,549432981,549432987,549432991,549432993,549433016" 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/Q9NZN9" 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=23746" 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=ENSG00000129221;t=ENST00000381129" 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=AIPL1" 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=AIPL1" 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+23746" 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/AIPL1" 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:23746" 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/23746" 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=chr17&hgg_gene=ENST00000381129.8&hgg_start=6423738&hgg_end=6435121&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:359" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604392[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=604392[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/AIPL1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000129221" 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=AIPL1" 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=AIPL1" 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=AIPL1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.retina-international.org/files/sci-news/aipl1mut.htm" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=AIPL1&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/PA24653" 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:359" 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:2148800" 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/AIPL1#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:2148800" 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/23746/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=23746" 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-131121-577" 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:23746" 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=AIPL1&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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604392
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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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ARYLHYDROCARBON-INTERACTING RECEPTOR PROTEIN-LIKE 1; AIPL1
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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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<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=AIPL1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">AIPL1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/17/115?start=-3&limit=10&highlight=115">17p13.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:6423738-6435121&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'})">17:6,423,738-6,435,121</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="3">
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<span class="mim-font">
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<p><a href="#10" class="mim-tip-reference" title="Sohocki, M. M., Malone, K. A., Sullivan, L. S., Diager, S. P. <strong>Localization of retina/pineal-expressed sequences: identification of novel candidate genes for inherited retinal disorders.</strong> Genomics 58: 29-33, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10331942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10331942</a>] [<a href="https://doi.org/10.1006/geno.1999.5810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10331942">Sohocki et al. (1999)</a> mapped sequence tagged sites (STSs) designed to the retinal/pineal-expressed EST clusters to 17p13.3 near a retinitis pigmentosa (RP13; <a href="/entry/600059">600059</a>) candidate region. Further testing refined the localization to 17p13.1, within the candidate region for Leber congenital amaurosis-4 (LCA4; <a href="/entry/604393">604393</a>) and approximately 2.5 Mb distal to GUCY2D (<a href="/entry/600179">600179</a>), which is mutant in LCA1 (<a href="/entry/204000">204000</a>). <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> confirmed this localization by fluorescence in situ hybridization. The results were consistent with the placement of AIPL1 in the Stanford G3 radiation hybrid panel. By cDNA sequencing of the 2 clusters, they determined that the ESTs represented transcripts of 1 gene. The protein encoded by this gene was named 'arylhydrocarbon receptor interacting protein-like 1' because of its similarity to arylhydrocarbon receptor-interacting protein (AIP), a member of the FK506-binding protein (FABP) family. The predicted 384-amino acid protein contains 3 tetratricopeptide motifs and a 56-amino acid proline-rich 'hinge' region near the C terminus that is present only in primate AIPL1. Northern blot hybridization identified mRNA molecules of the predicted size in total retinal RNA. The probe also cross-hybridized to 18s rRNA in the retina. In situ hybridization indicated expression in rat and mouse pineal gland, a high level of expression in adult mouse photoreceptors, and no expression in cornea. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10331942+10615133" 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="Sohocki, M. M., Malone, K. A., Sullivan, L. S., Diager, S. P. <strong>Localization of retina/pineal-expressed sequences: identification of novel candidate genes for inherited retinal disorders.</strong> Genomics 58: 29-33, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10331942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10331942</a>] [<a href="https://doi.org/10.1006/geno.1999.5810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10331942">Sohocki et al. (1999)</a> identified the AIPL1 gene on chromosome 17p13.1, within the candidate region for LCA4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10331942" 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 a polyclonal antibody directed against AIPL1, <a href="#13" class="mim-tip-reference" title="van der Spuy, J., Chapple, J. P., Clark, B. J., Luthert, P. J., Sethi, C. S., Cheetham, M. E. <strong>The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina.</strong> Hum. Molec. Genet. 11: 823-831, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929855</a>] [<a href="https://doi.org/10.1093/hmg/11.7.823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11929855">van der Spuy et al. (2002)</a> screened human tissues and immortalized cell lines and revealed AIPL1 to be specific to human retina and cell lines of retinal origin (Y79 retinoblastoma cells). Within the retina, AIPL1 was detected only in the rod photoreceptor cells of the peripheral and central human retina. The AIPL1 staining pattern extended within the rod photoreceptor cells from the inner segments, through the rod nuclei to the rod photoreceptor synaptic spherules in the outer plexiform layer. AIPL1 was not detected in the cone photoreceptors of peripheral or central human retina. The authors hypothesized that AIPL1 may perform a function essential to the maintenance of rod photoreceptor function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11929855" 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="#2" class="mim-tip-reference" title="Akey, D. T., Zhu, X., Dyer, M., Li, A., Sorensen, A., Blackshaw,S., Fukuda-Kamitani, T., Daiger, S. P., Craft, C. M., Kamitani, T., Sohocki, M. M. <strong>The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1.</strong> Hum. Molec. Genet. 11: 2723-2733, 2002. Note: Erratum: Hum. Molec. Genet. 12: 451 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374762</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12374762[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/11.22.2723" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12374762">Akey et al. (2002)</a> performed a yeast 2-hybrid screen to identify AIPL1-interacting proteins in the retina. One of the identified interacting proteins corresponded to NEDD8 ultimate buster-1 (NUB1; <a href="/entry/607981">607981</a>). The AIPL1-NUB1 interaction was verified by coimmunoprecipitation studies in retinoblastoma cells, demonstrating that this interaction occurred within cells that share a number of features with retinal progenitor cells. In situ hybridization studies showed that both AIPL1 and NUB1 are expressed in the developing and adult retina. The authors hypothesized that the early-onset form of retinal degeneration seen in LCA patients with AIPL1 mutations may be due to a defect in NUB1 regulation of cell cycle progression during photoreceptor maturation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12374762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To understand the molecular basis of Leber congenital amaurosis caused by AIPL1 mutations, and to elucidate the normal function of AIPL1, <a href="#8" class="mim-tip-reference" title="Ramamurthy, V., Roberts, M., van den Akker, F., Niemi, G., Reh, T. A., Hurley, J. B. <strong>AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins.</strong> Proc. Nat. Acad. Sci. 100: 12630-12635, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14555765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14555765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14555765[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.2134194100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14555765">Ramamurthy et al. (2003)</a> performed a yeast 2-hybrid screen using AIPL1 as bait. The screen demonstrated that AIPL1 interacts specifically with farnesylated proteins. Mutations in AIPL1 linked to LCA compromise this activity. The findings suggest that the essential function of AIPL1 within photoreceptors requires interactions with farnesylated proteins. Analysis of isoprenylation in cultured human cells showed that AIPL1 enhances the processing of farnesylated proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14555765" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a Pakistani family in which Leber congenital amaurosis associated with anterior keratoconus mapped to 17p13.1 (LCA4; <a href="/entry/604393">604393</a>), but in a region distinct from that occupied by GUCY2D, the gene mutant in LCA1, <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> demonstrated homozygosity for a nonsense mutation in the AIPL1 gene (W278X; <a href="#0001">604392.0001</a>). In addition, they identified homozygous or compound heterozygous mutations in the AIPL1 gene in 4 of 14 unrelated LCA families (see <a href="#0002">604392.0002</a>-<a href="#0003">604392.0003</a>), and concluded that mutations in this gene may account for approximately 20% of recessive LCA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To determine more generally the prevalence of AIPL1 mutations in inherited retinal degenerative disease, <a href="#11" class="mim-tip-reference" title="Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., Daiger, S. P. <strong>Prevalence of AIPL1 mutations in inherited retinal degenerative disease.</strong> Molec. Genet. Metab. 70: 142-150, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10873396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10873396</a>] [<a href="https://doi.org/10.1006/mgme.2000.3001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10873396">Sohocki et al. (2000)</a> screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases. They identified 11 Leber congenital amaurosis families whose retinal disorder was caused by homozygosity or compound heterozygosity for AIPL1 mutations. They also identified affected individuals in 2 apparently dominant families, diagnosed with juvenile retinitis pigmentosa (see <a href="/entry/604393">604393</a>) or dominant cone-rod dystrophy (see <a href="/entry/604393">604393</a>), respectively, who were heterozygous for a 12-bp deletion (<a href="#0004">604392.0004</a>) in the AIPL1 gene. The results suggested that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10873396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>To investigate the essential role of AIPL1 in the retina, <a href="#7" class="mim-tip-reference" title="Ramamurthy, V., Niemi, G. A., Reh, T. A., Hurley, J. B. <strong>Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase.</strong> Proc. Nat. Acad. Sci. 101: 13897-13902, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365178</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15365178[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.0404197101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365178">Ramamurthy et al. (2004)</a> generated a mouse model of Leber congenital amaurosis by inactivating the Aipl1 gene. In Aipl1 -/- retinas, the outer nuclear layer developed normally, but rods and cones then quickly degenerated. Aipl1-null mice had highly disorganized, short, fragmented photoreceptor outer segments and lacked both rod and cone electroretinogram responses. Other studies indicated that Aipl1 can enhance protein farnesylation. Their study showed that rod cGMP phosphodiesterase (PDE; see <a href="/entry/180071">180071</a>), a farnesylated protein, is absent and that cGMP levels are elevated in Aipl1 -/- retinas before the onset of degeneration. These findings demonstrated that Aipl1 enhances the stability of PDE and is essential for photoreceptor viability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365178" 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="Liu, X., Bulgakov, O. V., Wen, X.-H., Woodruff, M. L., Pawlyk, B., Yang, J., Fain, G. L., Sandberg, M. A., Makino, C. L., Li, T. <strong>AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase.</strong> Proc. Nat. Acad. Sci. 101: 13903-13908, 2004. Note: Erratum: Proc. Nat. Acad. Sci. 102: 515 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15365173[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.0405160101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365173">Liu et al. (2004)</a> showed that knockdown of Aipl1 expression in mice produces a retinopathy similar to that of Leber congenital amaurosis, but over a more extended time course. Before any noticeable pathology, there was a reduction in the level of rod cGMP PDE proportional to the decrease in Aipl1 expression, whereas other photoreceptor proteins were unaffected. Consistent with less PDE in rods, flash responses had a delayed onset, a reduced gain, and a slower recovery of flash responses. <a href="#5" class="mim-tip-reference" title="Liu, X., Bulgakov, O. V., Wen, X.-H., Woodruff, M. L., Pawlyk, B., Yang, J., Fain, G. L., Sandberg, M. A., Makino, C. L., Li, T. <strong>AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase.</strong> Proc. Nat. Acad. Sci. 101: 13903-13908, 2004. Note: Erratum: Proc. Nat. Acad. Sci. 102: 515 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15365173[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.0405160101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15365173">Liu et al. (2004)</a> suggested that AIPL1 is a specialized chaperone required for rod PDE biosynthesis. Thus, loss of AIPL1 would result in a condition that mimics retinal degeneration in the rd mouse and in a subgroup of human patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15365173" 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="Makino, C. L., Wen, X.-H., Michaud, N., Peshenko, I. V., Pawlyk, B., Brush, R. S., Soloviev, M., Liu, X., Woodruff, M. L., Calvert, P. D., Savchenko, A. B., Anderson, R. E., Fain, G. L., Li, T., Sandberg, M. A., Dizhoor, A. M. <strong>Effects of low AIPL1 expression on phototransduction in rods.</strong> Invest. Ophthal. Vis. Sci. 47: 2185-2194, 2006. Note: Erratum: Ophthal. Vis. Sci. 47: 2279 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16639031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16639031</a>] [<a href="https://doi.org/10.1167/iovs.05-1341" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16639031">Makino et al. (2006)</a> investigated the impact of Aipl1 on photoreception in mouse rods. Reduced Aipl1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in calcium. Not all changes were attributable to decreased PDE or to elevated cGMP and calcium in darkness. Thus, <a href="#6" class="mim-tip-reference" title="Makino, C. L., Wen, X.-H., Michaud, N., Peshenko, I. V., Pawlyk, B., Brush, R. S., Soloviev, M., Liu, X., Woodruff, M. L., Calvert, P. D., Savchenko, A. B., Anderson, R. E., Fain, G. L., Li, T., Sandberg, M. A., Dizhoor, A. M. <strong>Effects of low AIPL1 expression on phototransduction in rods.</strong> Invest. Ophthal. Vis. Sci. 47: 2185-2194, 2006. Note: Erratum: Ophthal. Vis. Sci. 47: 2279 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16639031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16639031</a>] [<a href="https://doi.org/10.1167/iovs.05-1341" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16639031">Makino et al. (2006)</a> concluded that AIPL1 directly or indirectly affects more than one component of phototransduction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16639031" 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="Tan, M. H., Smith, A. J., Pawlyk, B., Xu, X., Liu, X., Bainbridge, J. B., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A., Li, T., Ali, R. R. <strong>Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors.</strong> Hum. Molec. Genet. 18: 2099-2114, 2009. Note: Erratum: Hum. Molec. Genet. 19: 735 only, 2010. Erratum: Hum. Molec. Genet. 32: 3391-3393, 2023; Erratum: Hum. Molec. Genet. 33: 931-933, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19299492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19299492</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19299492[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/ddp133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19299492">Tan et al. (2009)</a> evaluated whether adeno-associated virus (AAV)-mediated gene replacement therapy was able to improve photoreceptor function and survival in retinal degeneration associated with AIPL1 defects. Two mouse models of AIPL1 deficiency were used: the Aipl1-hypomorphic (h/h) mouse (with reduced Aipl1 levels and a relatively slow degeneration), and the Aipl1-null mouse (with no functional Aipl1 and a very rapid retinal degeneration). Two pseudotypes of recombinant AAV exhibiting different transduction kinetics were used for gene transfer. The authors demonstrated restoration of cellular function and preservation of photoreceptor cells and retinal function in Aipl1 h/h mice 28 weeks after subretinal injection of an AAV2/2 vector and in the light-accelerated Aipl1 h/h model and Aipl1-null mice using an AAV2/8 vector. <a href="#12" class="mim-tip-reference" title="Tan, M. H., Smith, A. J., Pawlyk, B., Xu, X., Liu, X., Bainbridge, J. B., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A., Li, T., Ali, R. R. <strong>Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors.</strong> Hum. Molec. Genet. 18: 2099-2114, 2009. Note: Erratum: Hum. Molec. Genet. 19: 735 only, 2010. Erratum: Hum. Molec. Genet. 32: 3391-3393, 2023; Erratum: Hum. Molec. Genet. 33: 931-933, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19299492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19299492</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19299492[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/ddp133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19299492">Tan et al. (2009)</a> established the potential of gene replacement therapy in varying rates of degeneration that reflect the clinical spectrum of disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19299492" 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="Kirschman, L. T., Kolandaivelu, S., Frederick, J. M., Dang, L., Goldberg, A. F. X., Baehr, W., Ramamurthy, V. <strong>The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells.</strong> Hum. Molec. Genet. 19: 1076-1087, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20042464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20042464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20042464[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/ddp571" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20042464">Kirschman et al. (2010)</a> transgenically expressed human AIPL1 exclusively in the rod photoreceptors of the Aipl1 -/- mouse. Transgenic expression of AIPL1 restored rod morphology and the rod-derived electroretinogram response, but cone photoreceptors were nonfunctional in the absence of AIPL1. Cone photoreceptors degenerated, but at a slower rate compared with Aipl1 -/- mice. This degeneration was linked to the highly reduced levels of cone PDE6 (<a href="/entry/180071">180071</a>) observed in the AIPL1 transgenic mice. The authors concluded that AIPL1 is needed for the proper functioning and survival of cone photoreceptors. However, rod photoreceptors may also provide support that partially preserves cone photoreceptors from rapid death in the absence of AIPL1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20042464" 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="Ku, C. A., Chiodo, V. A., Boye, S. L., Hayes, A., Goldberg, A. F. X., Hauswirth, W. W., Ramamurthy, V. <strong>Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model.</strong> Hum. Molec. Genet. 24: 670-684, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25274777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25274777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25274777[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/ddu487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25274777">Ku et al. (2015)</a> generated transgenic mice in which the endogenous Aipl1 gene was replaced by wildtype human AIPL1 or by human AIPL1 with the 12-bp in-frame deletion leading to deletion of 4 amino acids beginning at pro351 (P351del12; <a href="#0004">604392.0004</a>). Homozygous mice from both lines were normal, healthy, and fertile, with no gross morphologic abnormalities. However, P351del12 mice showed slow and progressive degeneration of cone photoreceptors compared with mice homozygous for wildtype human AIPL1. Electroretinography (ERG) analysis of P351del12 mice revealed drastically reduced photopic responses and reduced scotopic responses at an early age that were associated with decreased rod and cone phosphodiesterase-6 (see <a href="/entry/180071">180071</a>). These visual defects worsened rapidly and progressively as mice aged. Transgenic mice coexpressing wildtype human AIPL1 and P351del12 exhibited visual defects similar to those of P351del12 mice, indicating that P351del12 acted as dominant for visual deficits over wildtype human AIPL1. However, P351del12 expression did not affect visual responses in mice also expressing endogenous wildtype mouse Aipl1, and AAV-mediated overexpression of wildtype human AIPL1 rescued cone defects and visual function in P351del12 mice, likely due to drastically higher overexpression of AIPL1 via AAV-mediated delivery than in transgenic mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25274777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604392[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs62637014 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62637014;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/rs62637014?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=rs62637014" 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=rs62637014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In the original Pakistani family identified as LCA4 (<a href="/entry/604393">604393</a>) and in a second Pakistani family, whose LCA had been mapped to 17p13.1, <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> demonstrated homozygosity for a nonsense mutation (trp278 to ter; W278X), TGG-to-TGA, in the AIPL1 gene. The mutation segregated with disease in both families and was not found in 100 ethnically matched controls. The 2 families differed in haplotype (GCG and GAA, respectively) of the AIPL1 exon 3 polymorphisms, as well as for microsatellite markers tightly linked to AIPL1. These findings suggested that the W278X mutation causing LCA in these 2 families was not derived from a recent, common ancestor. In a European family (RFS127), <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> found homozygosity for the W278X mutation. In this case haplotype analysis of tightly linked microsatellite markers and of the AIPL1 exon 3 polymorphisms suggested that the mutations in the RFS127 family and the second Pakistani family were likely to have descended from a common ancestor; however, there was no indication of Pakistani origin in this family. Noting that AIPL1 is not expressed in the cornea and that affected members of the second Pakistani family and the European family who were homozygous for W278X had LCA without keratoconus, the authors suggested that the keratoconus present in affected members of the original LCA4 family was possibly secondary to eye rubbing due to the LCA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615133" 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 more extensive study, <a href="#11" class="mim-tip-reference" title="Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., Daiger, S. P. <strong>Prevalence of AIPL1 mutations in inherited retinal degenerative disease.</strong> Molec. Genet. Metab. 70: 142-150, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10873396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10873396</a>] [<a href="https://doi.org/10.1006/mgme.2000.3001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10873396">Sohocki et al. (2000)</a> found homozygosity for the W278X mutation in 3 of 13 families and compound heterozygosity in 3 additional families. The mutation was identified in affected individuals from multiple populations, including Pakistani, Spanish, French, and American. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10873396" 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>From a study of data on 42 patients from 18 countries with molecularly confirmed LCA4, <a href="#1" class="mim-tip-reference" title="Aboshiha, J., Dubis, A. M., van der Spuy, J., Nishiguchi, K. M., Cheeseman, E. W., Ayuso, C., Ehrenberg, M., Simonelli, F., Bainbridge, J. W., Michaelides, M. <strong>Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy.</strong> Ophthalmology 122: 862-864, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25596619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25596619</a>] [<a href="https://doi.org/10.1016/j.ophtha.2014.11.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25596619">Aboshiha et al. (2015)</a> found that W278X was the most common mutation, being found on one or more alleles in 26 patients (62%) and on both alleles in 15 patients (36%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25596619" 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 LEBER CONGENITAL AMAUROSIS 4</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005907 OR RCV000086209" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005907, RCV000086209" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005907...</a>
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<p>In 2 affected members of a European family with LCA4 (<a href="/entry/604393">604393</a>), <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> identified compound heterozygosity for the W278X mutation (<a href="#0001">604392.0001</a>) and a 2-bp deletion in codon 336 in the AIPL1 gene (ala336del2). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 LEBER CONGENITAL AMAUROSIS 4</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">rs62637012 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62637012;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=rs62637012" 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=rs62637012" 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=RCV000005908 OR RCV000086231 OR RCV004585988" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005908, RCV000086231, RCV004585988" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005908...</a>
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<p>In 3 affected members of a European family with LCA4 (<a href="/entry/604393">604393</a>), <a href="#9" class="mim-tip-reference" title="Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P. <strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong> Nature Genet. 24: 79-83, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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/10.1038/71732" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10615133">Sohocki et al. (2000)</a> found that Leber congenital amaurosis segregated with homozygosity for a T-to-C transition in the AIPL1 gene, predicted to encode a cys239-to-arg (C239R) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10615133" 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>.0004 RETINITIS PIGMENTOSA, JUVENILE, AIPL1-RELATED</strong>
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CONE-ROD DYSTROPHY, AIPL1-RELATED, INCLUDED
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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> rs281865195 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865195;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/rs281865195?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=rs281865195" 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=rs281865195" 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=RCV000005909 OR RCV000005910 OR RCV000086210 OR RCV001517242 OR RCV002222344 OR RCV004732531 OR RCV004814841" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005909, RCV000005910, RCV000086210, RCV001517242, RCV002222344, RCV004732531, RCV004814841" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005909...</a>
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<p>In affected individuals in 2 unrelated families with an apparently dominant retinal degenerative disorder, diagnosed as juvenile retinitis pigmentosa (see <a href="/entry/604393">604393</a>) in one and cone-rod dystrophy (see <a href="/entry/604393">604393</a>) in the other, <a href="#11" class="mim-tip-reference" title="Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., Daiger, S. P. <strong>Prevalence of AIPL1 mutations in inherited retinal degenerative disease.</strong> Molec. Genet. Metab. 70: 142-150, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10873396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10873396</a>] [<a href="https://doi.org/10.1006/mgme.2000.3001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10873396">Sohocki et al. (2000)</a> found heterozygosity for a 12-bp AIPL1 deletion, pro351del12, or del1053-1064, in the 'hinge' region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10873396" 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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Aboshiha, J., Dubis, A. M., van der Spuy, J., Nishiguchi, K. M., Cheeseman, E. W., Ayuso, C., Ehrenberg, M., Simonelli, F., Bainbridge, J. W., Michaelides, M.
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<strong>Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy.</strong>
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Ophthalmology 122: 862-864, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25596619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25596619</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25596619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ophtha.2014.11.019" target="_blank">Full Text</a>]
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Akey, D. T., Zhu, X., Dyer, M., Li, A., Sorensen, A., Blackshaw,S., Fukuda-Kamitani, T., Daiger, S. P., Craft, C. M., Kamitani, T., Sohocki, M. M.
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<strong>The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1.</strong>
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Hum. Molec. Genet. 11: 2723-2733, 2002. Note: Erratum: Hum. Molec. Genet. 12: 451 only, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12374762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12374762</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12374762[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=12374762" 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/11.22.2723" target="_blank">Full Text</a>]
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Kirschman, L. T., Kolandaivelu, S., Frederick, J. M., Dang, L., Goldberg, A. F. X., Baehr, W., Ramamurthy, V.
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<strong>The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells.</strong>
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Hum. Molec. Genet. 19: 1076-1087, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20042464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20042464</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20042464[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=20042464" 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/ddp571" target="_blank">Full Text</a>]
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<a id="Ku2015" class="mim-anchor"></a>
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<div class="">
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Ku, C. A., Chiodo, V. A., Boye, S. L., Hayes, A., Goldberg, A. F. X., Hauswirth, W. W., Ramamurthy, V.
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<strong>Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model.</strong>
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Hum. Molec. Genet. 24: 670-684, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25274777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25274777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25274777[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=25274777" 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/ddu487" target="_blank">Full Text</a>]
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<a id="Liu2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Liu, X., Bulgakov, O. V., Wen, X.-H., Woodruff, M. L., Pawlyk, B., Yang, J., Fain, G. L., Sandberg, M. A., Makino, C. L., Li, T.
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<strong>AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase.</strong>
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Proc. Nat. Acad. Sci. 101: 13903-13908, 2004. Note: Erratum: Proc. Nat. Acad. Sci. 102: 515 only, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15365173[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=15365173" 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.0405160101" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Makino2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Makino, C. L., Wen, X.-H., Michaud, N., Peshenko, I. V., Pawlyk, B., Brush, R. S., Soloviev, M., Liu, X., Woodruff, M. L., Calvert, P. D., Savchenko, A. B., Anderson, R. E., Fain, G. L., Li, T., Sandberg, M. A., Dizhoor, A. M.
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<strong>Effects of low AIPL1 expression on phototransduction in rods.</strong>
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Invest. Ophthal. Vis. Sci. 47: 2185-2194, 2006. Note: Erratum: Ophthal. Vis. Sci. 47: 2279 only, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16639031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16639031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16639031" 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/10.1167/iovs.05-1341" target="_blank">Full Text</a>]
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<a id="Ramamurthy2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ramamurthy, V., Niemi, G. A., Reh, T. A., Hurley, J. B.
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<strong>Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase.</strong>
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Proc. Nat. Acad. Sci. 101: 13897-13902, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15365178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15365178</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15365178[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=15365178" 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.0404197101" target="_blank">Full Text</a>]
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<a id="Ramamurthy2003" class="mim-anchor"></a>
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Ramamurthy, V., Roberts, M., van den Akker, F., Niemi, G., Reh, T. A., Hurley, J. B.
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<strong>AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins.</strong>
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Proc. Nat. Acad. Sci. 100: 12630-12635, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14555765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14555765</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14555765[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=14555765" 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.2134194100" target="_blank">Full Text</a>]
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<a id="Sohocki2000" class="mim-anchor"></a>
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<div class="">
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Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P.
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<strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong>
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Nature Genet. 24: 79-83, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10615133/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10615133</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10615133[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=10615133" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/71732" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Sohocki1999" class="mim-anchor"></a>
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Sohocki, M. M., Malone, K. A., Sullivan, L. S., Diager, S. P.
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<strong>Localization of retina/pineal-expressed sequences: identification of novel candidate genes for inherited retinal disorders.</strong>
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Genomics 58: 29-33, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10331942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10331942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10331942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1999.5810" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Sohocki2000" class="mim-anchor"></a>
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Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., Daiger, S. P.
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<strong>Prevalence of AIPL1 mutations in inherited retinal degenerative disease.</strong>
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Molec. Genet. Metab. 70: 142-150, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10873396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10873396</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10873396" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/mgme.2000.3001" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Tan2009" class="mim-anchor"></a>
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Tan, M. H., Smith, A. J., Pawlyk, B., Xu, X., Liu, X., Bainbridge, J. B., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A., Li, T., Ali, R. R.
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<strong>Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors.</strong>
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Hum. Molec. Genet. 18: 2099-2114, 2009. Note: Erratum: Hum. Molec. Genet. 19: 735 only, 2010. Erratum: Hum. Molec. Genet. 32: 3391-3393, 2023; Erratum: Hum. Molec. Genet. 33: 931-933, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19299492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19299492</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19299492[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=19299492" 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/ddp133" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="van der Spuy2002" class="mim-anchor"></a>
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van der Spuy, J., Chapple, J. P., Clark, B. J., Luthert, P. J., Sethi, C. S., Cheetham, M. E.
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<strong>The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina.</strong>
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Hum. Molec. Genet. 11: 823-831, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11929855/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11929855</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11929855" 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/11.7.823" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Bao Lige - updated : 05/13/2020
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<span class="mim-text-font">
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Jane Kelly - updated : 09/11/2015<br>Marla J. F. O'Neill - updated : 5/4/2012<br>George E. Tiller - updated : 11/10/2011<br>Marla J. F. O'Neill - updated : 4/6/2010<br>George E. Tiller - updated : 2/25/2010<br>Jane Kelly - updated : 12/7/2006<br>Victor A. McKusick - updated : 11/24/2004<br>Victor A. McKusick - updated : 7/7/2004<br>George E. Tiller - updated : 2/12/2004<br>George E. Tiller - updated : 10/29/2002<br>Victor A. McKusick - updated : 2/26/2001
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Victor A. McKusick : 12/29/1999
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carol : 07/19/2024
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carol : 01/26/2024<br>mgross : 05/13/2020<br>carol : 09/11/2015<br>terry : 3/14/2013<br>terry : 9/17/2012<br>terry : 8/8/2012<br>carol : 5/4/2012<br>terry : 5/4/2012<br>alopez : 11/16/2011<br>terry : 11/10/2011<br>carol : 4/6/2010<br>wwang : 3/11/2010<br>terry : 2/25/2010<br>carol : 4/3/2009<br>alopez : 4/1/2009<br>alopez : 2/18/2009<br>carol : 12/7/2006<br>carol : 12/7/2006<br>terry : 12/7/2006<br>mgross : 2/1/2005<br>alopez : 12/7/2004<br>terry : 11/24/2004<br>alopez : 7/12/2004<br>terry : 7/7/2004<br>cwells : 2/12/2004<br>cwells : 10/29/2002<br>mcapotos : 3/5/2001<br>mcapotos : 3/1/2001<br>terry : 2/26/2001<br>terry : 10/6/2000<br>alopez : 12/29/1999
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ARYLHYDROCARBON-INTERACTING RECEPTOR PROTEIN-LIKE 1; AIPL1
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: AIPL1</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: 17p13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:6,423,738-6,435,121 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="3">
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<span class="mim-font">
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17p13.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Cone-rod dystrophy
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</span>
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</td>
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<td>
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<span class="mim-font">
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604393
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Leber congenital amaurosis 4
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</span>
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</td>
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<td>
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<span class="mim-font">
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604393
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Retinitis pigmentosa, juvenile
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</span>
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</td>
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<td>
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<span class="mim-font">
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604393
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sohocki et al. (1999) mapped sequence tagged sites (STSs) designed to the retinal/pineal-expressed EST clusters to 17p13.3 near a retinitis pigmentosa (RP13; 600059) candidate region. Further testing refined the localization to 17p13.1, within the candidate region for Leber congenital amaurosis-4 (LCA4; 604393) and approximately 2.5 Mb distal to GUCY2D (600179), which is mutant in LCA1 (204000). Sohocki et al. (2000) confirmed this localization by fluorescence in situ hybridization. The results were consistent with the placement of AIPL1 in the Stanford G3 radiation hybrid panel. By cDNA sequencing of the 2 clusters, they determined that the ESTs represented transcripts of 1 gene. The protein encoded by this gene was named 'arylhydrocarbon receptor interacting protein-like 1' because of its similarity to arylhydrocarbon receptor-interacting protein (AIP), a member of the FK506-binding protein (FABP) family. The predicted 384-amino acid protein contains 3 tetratricopeptide motifs and a 56-amino acid proline-rich 'hinge' region near the C terminus that is present only in primate AIPL1. Northern blot hybridization identified mRNA molecules of the predicted size in total retinal RNA. The probe also cross-hybridized to 18s rRNA in the retina. In situ hybridization indicated expression in rat and mouse pineal gland, a high level of expression in adult mouse photoreceptors, and no expression in cornea. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Sohocki et al. (1999) identified the AIPL1 gene on chromosome 17p13.1, within the candidate region for LCA4. </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 a polyclonal antibody directed against AIPL1, van der Spuy et al. (2002) screened human tissues and immortalized cell lines and revealed AIPL1 to be specific to human retina and cell lines of retinal origin (Y79 retinoblastoma cells). Within the retina, AIPL1 was detected only in the rod photoreceptor cells of the peripheral and central human retina. The AIPL1 staining pattern extended within the rod photoreceptor cells from the inner segments, through the rod nuclei to the rod photoreceptor synaptic spherules in the outer plexiform layer. AIPL1 was not detected in the cone photoreceptors of peripheral or central human retina. The authors hypothesized that AIPL1 may perform a function essential to the maintenance of rod photoreceptor function. </p><p>Akey et al. (2002) performed a yeast 2-hybrid screen to identify AIPL1-interacting proteins in the retina. One of the identified interacting proteins corresponded to NEDD8 ultimate buster-1 (NUB1; 607981). The AIPL1-NUB1 interaction was verified by coimmunoprecipitation studies in retinoblastoma cells, demonstrating that this interaction occurred within cells that share a number of features with retinal progenitor cells. In situ hybridization studies showed that both AIPL1 and NUB1 are expressed in the developing and adult retina. The authors hypothesized that the early-onset form of retinal degeneration seen in LCA patients with AIPL1 mutations may be due to a defect in NUB1 regulation of cell cycle progression during photoreceptor maturation. </p><p>To understand the molecular basis of Leber congenital amaurosis caused by AIPL1 mutations, and to elucidate the normal function of AIPL1, Ramamurthy et al. (2003) performed a yeast 2-hybrid screen using AIPL1 as bait. The screen demonstrated that AIPL1 interacts specifically with farnesylated proteins. Mutations in AIPL1 linked to LCA compromise this activity. The findings suggest that the essential function of AIPL1 within photoreceptors requires interactions with farnesylated proteins. Analysis of isoprenylation in cultured human cells showed that AIPL1 enhances the processing of farnesylated proteins. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a Pakistani family in which Leber congenital amaurosis associated with anterior keratoconus mapped to 17p13.1 (LCA4; 604393), but in a region distinct from that occupied by GUCY2D, the gene mutant in LCA1, Sohocki et al. (2000) demonstrated homozygosity for a nonsense mutation in the AIPL1 gene (W278X; 604392.0001). In addition, they identified homozygous or compound heterozygous mutations in the AIPL1 gene in 4 of 14 unrelated LCA families (see 604392.0002-604392.0003), and concluded that mutations in this gene may account for approximately 20% of recessive LCA. </p><p>To determine more generally the prevalence of AIPL1 mutations in inherited retinal degenerative disease, Sohocki et al. (2000) screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases. They identified 11 Leber congenital amaurosis families whose retinal disorder was caused by homozygosity or compound heterozygosity for AIPL1 mutations. They also identified affected individuals in 2 apparently dominant families, diagnosed with juvenile retinitis pigmentosa (see 604393) or dominant cone-rod dystrophy (see 604393), respectively, who were heterozygous for a 12-bp deletion (604392.0004) in the AIPL1 gene. The results suggested that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To investigate the essential role of AIPL1 in the retina, Ramamurthy et al. (2004) generated a mouse model of Leber congenital amaurosis by inactivating the Aipl1 gene. In Aipl1 -/- retinas, the outer nuclear layer developed normally, but rods and cones then quickly degenerated. Aipl1-null mice had highly disorganized, short, fragmented photoreceptor outer segments and lacked both rod and cone electroretinogram responses. Other studies indicated that Aipl1 can enhance protein farnesylation. Their study showed that rod cGMP phosphodiesterase (PDE; see 180071), a farnesylated protein, is absent and that cGMP levels are elevated in Aipl1 -/- retinas before the onset of degeneration. These findings demonstrated that Aipl1 enhances the stability of PDE and is essential for photoreceptor viability. </p><p>Liu et al. (2004) showed that knockdown of Aipl1 expression in mice produces a retinopathy similar to that of Leber congenital amaurosis, but over a more extended time course. Before any noticeable pathology, there was a reduction in the level of rod cGMP PDE proportional to the decrease in Aipl1 expression, whereas other photoreceptor proteins were unaffected. Consistent with less PDE in rods, flash responses had a delayed onset, a reduced gain, and a slower recovery of flash responses. Liu et al. (2004) suggested that AIPL1 is a specialized chaperone required for rod PDE biosynthesis. Thus, loss of AIPL1 would result in a condition that mimics retinal degeneration in the rd mouse and in a subgroup of human patients. </p><p>Makino et al. (2006) investigated the impact of Aipl1 on photoreception in mouse rods. Reduced Aipl1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in calcium. Not all changes were attributable to decreased PDE or to elevated cGMP and calcium in darkness. Thus, Makino et al. (2006) concluded that AIPL1 directly or indirectly affects more than one component of phototransduction. </p><p>Tan et al. (2009) evaluated whether adeno-associated virus (AAV)-mediated gene replacement therapy was able to improve photoreceptor function and survival in retinal degeneration associated with AIPL1 defects. Two mouse models of AIPL1 deficiency were used: the Aipl1-hypomorphic (h/h) mouse (with reduced Aipl1 levels and a relatively slow degeneration), and the Aipl1-null mouse (with no functional Aipl1 and a very rapid retinal degeneration). Two pseudotypes of recombinant AAV exhibiting different transduction kinetics were used for gene transfer. The authors demonstrated restoration of cellular function and preservation of photoreceptor cells and retinal function in Aipl1 h/h mice 28 weeks after subretinal injection of an AAV2/2 vector and in the light-accelerated Aipl1 h/h model and Aipl1-null mice using an AAV2/8 vector. Tan et al. (2009) established the potential of gene replacement therapy in varying rates of degeneration that reflect the clinical spectrum of disease. </p><p>Kirschman et al. (2010) transgenically expressed human AIPL1 exclusively in the rod photoreceptors of the Aipl1 -/- mouse. Transgenic expression of AIPL1 restored rod morphology and the rod-derived electroretinogram response, but cone photoreceptors were nonfunctional in the absence of AIPL1. Cone photoreceptors degenerated, but at a slower rate compared with Aipl1 -/- mice. This degeneration was linked to the highly reduced levels of cone PDE6 (180071) observed in the AIPL1 transgenic mice. The authors concluded that AIPL1 is needed for the proper functioning and survival of cone photoreceptors. However, rod photoreceptors may also provide support that partially preserves cone photoreceptors from rapid death in the absence of AIPL1. </p><p>Ku et al. (2015) generated transgenic mice in which the endogenous Aipl1 gene was replaced by wildtype human AIPL1 or by human AIPL1 with the 12-bp in-frame deletion leading to deletion of 4 amino acids beginning at pro351 (P351del12; 604392.0004). Homozygous mice from both lines were normal, healthy, and fertile, with no gross morphologic abnormalities. However, P351del12 mice showed slow and progressive degeneration of cone photoreceptors compared with mice homozygous for wildtype human AIPL1. Electroretinography (ERG) analysis of P351del12 mice revealed drastically reduced photopic responses and reduced scotopic responses at an early age that were associated with decreased rod and cone phosphodiesterase-6 (see 180071). These visual defects worsened rapidly and progressively as mice aged. Transgenic mice coexpressing wildtype human AIPL1 and P351del12 exhibited visual defects similar to those of P351del12 mice, indicating that P351del12 acted as dominant for visual deficits over wildtype human AIPL1. However, P351del12 expression did not affect visual responses in mice also expressing endogenous wildtype mouse Aipl1, and AAV-mediated overexpression of wildtype human AIPL1 rescued cone defects and visual function in P351del12 mice, likely due to drastically higher overexpression of AIPL1 via AAV-mediated delivery than in transgenic mice. </p>
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</span>
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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>4 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 LEBER CONGENITAL AMAUROSIS 4</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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AIPL1, TRP278TER
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<br />
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SNP: rs62637014,
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gnomAD: rs62637014,
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ClinVar: RCV000005906, RCV000086235, RCV000365317, RCV000505017, RCV001074840, RCV002496274, RCV004786238
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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 the original Pakistani family identified as LCA4 (604393) and in a second Pakistani family, whose LCA had been mapped to 17p13.1, Sohocki et al. (2000) demonstrated homozygosity for a nonsense mutation (trp278 to ter; W278X), TGG-to-TGA, in the AIPL1 gene. The mutation segregated with disease in both families and was not found in 100 ethnically matched controls. The 2 families differed in haplotype (GCG and GAA, respectively) of the AIPL1 exon 3 polymorphisms, as well as for microsatellite markers tightly linked to AIPL1. These findings suggested that the W278X mutation causing LCA in these 2 families was not derived from a recent, common ancestor. In a European family (RFS127), Sohocki et al. (2000) found homozygosity for the W278X mutation. In this case haplotype analysis of tightly linked microsatellite markers and of the AIPL1 exon 3 polymorphisms suggested that the mutations in the RFS127 family and the second Pakistani family were likely to have descended from a common ancestor; however, there was no indication of Pakistani origin in this family. Noting that AIPL1 is not expressed in the cornea and that affected members of the second Pakistani family and the European family who were homozygous for W278X had LCA without keratoconus, the authors suggested that the keratoconus present in affected members of the original LCA4 family was possibly secondary to eye rubbing due to the LCA. </p><p>In a more extensive study, Sohocki et al. (2000) found homozygosity for the W278X mutation in 3 of 13 families and compound heterozygosity in 3 additional families. The mutation was identified in affected individuals from multiple populations, including Pakistani, Spanish, French, and American. </p><p>From a study of data on 42 patients from 18 countries with molecularly confirmed LCA4, Aboshiha et al. (2015) found that W278X was the most common mutation, being found on one or more alleles in 26 patients (62%) and on both alleles in 15 patients (36%). </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 LEBER CONGENITAL AMAUROSIS 4</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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AIPL1, 2-BP DEL
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<br />
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SNP: rs62637016,
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ClinVar: RCV000005907, RCV000086209
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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 affected members of a European family with LCA4 (604393), Sohocki et al. (2000) identified compound heterozygosity for the W278X mutation (604392.0001) and a 2-bp deletion in codon 336 in the AIPL1 gene (ala336del2). </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 LEBER CONGENITAL AMAUROSIS 4</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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AIPL1, CYS239ARG
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<br />
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SNP: rs62637012,
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ClinVar: RCV000005908, RCV000086231, RCV004585988
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected members of a European family with LCA4 (604393), Sohocki et al. (2000) found that Leber congenital amaurosis segregated with homozygosity for a T-to-C transition in the AIPL1 gene, predicted to encode a cys239-to-arg (C239R) amino acid substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 RETINITIS PIGMENTOSA, JUVENILE, AIPL1-RELATED</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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CONE-ROD DYSTROPHY, AIPL1-RELATED, 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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AIPL1, 12-BP DEL, NT1053
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<br />
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SNP: rs281865195,
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gnomAD: rs281865195,
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ClinVar: RCV000005909, RCV000005910, RCV000086210, RCV001517242, RCV002222344, RCV004732531, RCV004814841
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<p>In affected individuals in 2 unrelated families with an apparently dominant retinal degenerative disorder, diagnosed as juvenile retinitis pigmentosa (see 604393) in one and cone-rod dystrophy (see 604393) in the other, Sohocki et al. (2000) found heterozygosity for a 12-bp AIPL1 deletion, pro351del12, or del1053-1064, in the 'hinge' region of the protein. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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Aboshiha, J., Dubis, A. M., van der Spuy, J., Nishiguchi, K. M., Cheeseman, E. W., Ayuso, C., Ehrenberg, M., Simonelli, F., Bainbridge, J. W., Michaelides, M.
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<strong>Preserved outer retina in AIPL1 Leber's congenital amaurosis: implications for gene therapy.</strong>
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Ophthalmology 122: 862-864, 2015.
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[PubMed: 25596619]
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[Full Text: https://doi.org/10.1016/j.ophtha.2014.11.019]
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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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Akey, D. T., Zhu, X., Dyer, M., Li, A., Sorensen, A., Blackshaw,S., Fukuda-Kamitani, T., Daiger, S. P., Craft, C. M., Kamitani, T., Sohocki, M. M.
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<strong>The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1.</strong>
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Hum. Molec. Genet. 11: 2723-2733, 2002. Note: Erratum: Hum. Molec. Genet. 12: 451 only, 2003.
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[PubMed: 12374762]
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[Full Text: https://doi.org/10.1093/hmg/11.22.2723]
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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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Kirschman, L. T., Kolandaivelu, S., Frederick, J. M., Dang, L., Goldberg, A. F. X., Baehr, W., Ramamurthy, V.
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<strong>The Leber congenital amaurosis protein, AIPL1, is needed for the viability and functioning of cone photoreceptor cells.</strong>
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Hum. Molec. Genet. 19: 1076-1087, 2010.
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[PubMed: 20042464]
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[Full Text: https://doi.org/10.1093/hmg/ddp571]
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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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Ku, C. A., Chiodo, V. A., Boye, S. L., Hayes, A., Goldberg, A. F. X., Hauswirth, W. W., Ramamurthy, V.
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<strong>Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model.</strong>
|
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Hum. Molec. Genet. 24: 670-684, 2015.
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[PubMed: 25274777]
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[Full Text: https://doi.org/10.1093/hmg/ddu487]
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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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Liu, X., Bulgakov, O. V., Wen, X.-H., Woodruff, M. L., Pawlyk, B., Yang, J., Fain, G. L., Sandberg, M. A., Makino, C. L., Li, T.
|
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<strong>AIPL1, the protein that is defective in Leber congenital amaurosis, is essential for the biosynthesis of retinal rod cGMP phosphodiesterase.</strong>
|
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Proc. Nat. Acad. Sci. 101: 13903-13908, 2004. Note: Erratum: Proc. Nat. Acad. Sci. 102: 515 only, 2005.
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[PubMed: 15365173]
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[Full Text: https://doi.org/10.1073/pnas.0405160101]
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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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Makino, C. L., Wen, X.-H., Michaud, N., Peshenko, I. V., Pawlyk, B., Brush, R. S., Soloviev, M., Liu, X., Woodruff, M. L., Calvert, P. D., Savchenko, A. B., Anderson, R. E., Fain, G. L., Li, T., Sandberg, M. A., Dizhoor, A. M.
|
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<strong>Effects of low AIPL1 expression on phototransduction in rods.</strong>
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Invest. Ophthal. Vis. Sci. 47: 2185-2194, 2006. Note: Erratum: Ophthal. Vis. Sci. 47: 2279 only, 2006.
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[PubMed: 16639031]
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[Full Text: https://doi.org/10.1167/iovs.05-1341]
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<p class="mim-text-font">
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Ramamurthy, V., Niemi, G. A., Reh, T. A., Hurley, J. B.
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<strong>Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase.</strong>
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Proc. Nat. Acad. Sci. 101: 13897-13902, 2004.
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[PubMed: 15365178]
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[Full Text: https://doi.org/10.1073/pnas.0404197101]
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<p class="mim-text-font">
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Ramamurthy, V., Roberts, M., van den Akker, F., Niemi, G., Reh, T. A., Hurley, J. B.
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<strong>AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins.</strong>
|
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Proc. Nat. Acad. Sci. 100: 12630-12635, 2003.
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[PubMed: 14555765]
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[Full Text: https://doi.org/10.1073/pnas.2134194100]
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<p class="mim-text-font">
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Sohocki, M. M., Bowne, S. J., Sullivan, L. S., Blackshaw, S., Cepko, C. L., Payne, A. M., Bhattacharya, S. S., Khaliq, S., Mehdi, S. Q., Birch, D. G., Harrison, W. R., Elder, F. F. B., Heckenlively, J. R., Daiger, S. P.
|
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<strong>Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis.</strong>
|
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Nature Genet. 24: 79-83, 2000.
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[PubMed: 10615133]
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[Full Text: https://doi.org/10.1038/71732]
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</p>
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<p class="mim-text-font">
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Sohocki, M. M., Malone, K. A., Sullivan, L. S., Diager, S. P.
|
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<strong>Localization of retina/pineal-expressed sequences: identification of novel candidate genes for inherited retinal disorders.</strong>
|
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Genomics 58: 29-33, 1999.
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[PubMed: 10331942]
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[Full Text: https://doi.org/10.1006/geno.1999.5810]
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</p>
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</li>
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<p class="mim-text-font">
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Sohocki, M. M., Perrault, I., Leroy, B. P., Payne, A. M., Dharmaraj, S., Bhattacharya, S. S., Kaplan, J., Maumenee, I. H., Koenekoop, R., Meire, F. M., Birch, D. G., Heckenlively, J. R., Daiger, S. P.
|
|
<strong>Prevalence of AIPL1 mutations in inherited retinal degenerative disease.</strong>
|
|
Molec. Genet. Metab. 70: 142-150, 2000.
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[PubMed: 10873396]
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[Full Text: https://doi.org/10.1006/mgme.2000.3001]
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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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Tan, M. H., Smith, A. J., Pawlyk, B., Xu, X., Liu, X., Bainbridge, J. B., Basche, M., McIntosh, J., Tran, H. V., Nathwani, A., Li, T., Ali, R. R.
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|
<strong>Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors.</strong>
|
|
Hum. Molec. Genet. 18: 2099-2114, 2009. Note: Erratum: Hum. Molec. Genet. 19: 735 only, 2010. Erratum: Hum. Molec. Genet. 32: 3391-3393, 2023; Erratum: Hum. Molec. Genet. 33: 931-933, 2024.
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[PubMed: 19299492]
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[Full Text: https://doi.org/10.1093/hmg/ddp133]
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<li>
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<p class="mim-text-font">
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van der Spuy, J., Chapple, J. P., Clark, B. J., Luthert, P. J., Sethi, C. S., Cheetham, M. E.
|
|
<strong>The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina.</strong>
|
|
Hum. Molec. Genet. 11: 823-831, 2002.
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[PubMed: 11929855]
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[Full Text: https://doi.org/10.1093/hmg/11.7.823]
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Bao Lige - updated : 05/13/2020<br>Jane Kelly - updated : 09/11/2015<br>Marla J. F. O'Neill - updated : 5/4/2012<br>George E. Tiller - updated : 11/10/2011<br>Marla J. F. O'Neill - updated : 4/6/2010<br>George E. Tiller - updated : 2/25/2010<br>Jane Kelly - updated : 12/7/2006<br>Victor A. McKusick - updated : 11/24/2004<br>Victor A. McKusick - updated : 7/7/2004<br>George E. Tiller - updated : 2/12/2004<br>George E. Tiller - updated : 10/29/2002<br>Victor A. McKusick - updated : 2/26/2001
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