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Entry
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- *600528 - CARNITINE PALMITOYLTRANSFERASE I, LIVER; CPT1A
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600528</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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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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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/600528">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></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 role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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</nav>
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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=ENSG00000110090;t=ENST00000265641" 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=1374" 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=600528" 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=ENSG00000110090;t=ENST00000265641" 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_001031847,NM_001876,XM_017017220,XM_047426376,XM_047426377" 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_001876" 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=600528" 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=02755&isoform_id=02755_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/CPT1A" 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/755646,12652865,17066276,18693171,27368653,32879925,56405343,73623028,73623030,119595127,119595128,189067245,1034572036,2217281175,2217281177,2462522979,2462522981,2462522983" 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/P50416" 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=1374" 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=ENSG00000110090;t=ENST00000265641" 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=CPT1A" 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=CPT1A" 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+1374" 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/CPT1A" 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:1374" 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/1374" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr11&hgg_gene=ENST00000265641.10&hgg_start=68754620&hgg_end=68844277&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:2328" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2328" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/cpt1a" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600528[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 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=600528[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000110090" 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=CPT1A" 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=CPT1A" 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=CPT1A" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CPT1A&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/PA26847" 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:2328" 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/FBgn0261862.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:1098296" 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/CPT1A#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:1098296" 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/1374/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=1374" 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=WBGene00012907;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-3250" 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:1374" 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=CPT1A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 238001003<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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600528
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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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CARNITINE PALMITOYLTRANSFERASE I, LIVER; CPT1A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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CPT IA<br />
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CPT I, LIVER<br />
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CPT1
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CPT1A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CPT1A</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/11/688?start=-3&limit=10&highlight=688">11q13.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:68754620-68844277&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">11:68,754,620-68,844,277</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">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
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<th>
|
|
Location
|
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</th>
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<th>
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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>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/688?start=-3&limit=10&highlight=688">
|
|
11q13.3
|
|
</a>
|
|
</span>
|
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</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
CPT deficiency, hepatic, type IA
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/255120"> 255120 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/600528" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/600528" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<p>The CPT1A gene encodes carnitine palmitoyltransferase IA, a liver enzyme involved in fatty acid oxidation. The carnitine palmitoyltransferase (CPT; <a href="https://enzyme.expasy.org/EC/2.3.1.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.3.1.21</a>) enzyme system, in conjunction with acyl-CoA synthetase and carnitine/acylcarnitine translocase (<a href="/entry/613698">613698</a>), provides the mechanism whereby long-chain fatty acids are transferred from the cytosol to the mitochondrial matrix to undergo beta-oxidation for energy production. The CPT I isozymes (CPT1A and CPT1B; <a href="/entry/601987">601987</a>) are located in the mitochondrial outer membrane and are detergent-labile, whereas CPT II (<a href="/entry/600650">600650</a>) is located in the inner mitochondrial membrane and is detergent-stable (<a href="#4" class="mim-tip-reference" title="Bieber, L. L. <strong>Carnitine.</strong> Annu. Rev. Biochem. 57: 261-283, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3052273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3052273</a>] [<a href="https://doi.org/10.1146/annurev.bi.57.070188.001401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3052273">Bieber, 1988</a>; <a href="#16" class="mim-tip-reference" title="Murthy, M. S. R., Pande, S. V. <strong>Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane.</strong> Proc. Nat. Acad. Sci. 84: 378-382, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3540964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3540964</a>] [<a href="https://doi.org/10.1073/pnas.84.2.378" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3540964">Murthy and Pande, 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3052273+3540964" 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>From a rat liver cDNA library, <a href="#10" class="mim-tip-reference" title="Esser, V., Britton, C. H., Weis, B. C., Foster, D. W., McGarry, J. D. <strong>Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I: direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function.</strong> J. Biol. Chem. 268: 5817-5822, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8449948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8449948</a>]" pmid="8449948">Esser et al. (1993)</a> isolated a cDNA corresponding to carnitine palmitoyltransferase I. The deduced 773-amino acid protein has a molecular mass of 88 kD. A 4.7-kb mRNA was detected in rat liver. The authors suggested that the de novo synthesized enzyme is targeted to the mitochondrial outer membrane by a leader peptide, and that the mature protein anchors to the membrane through a 20-amino acid region near the N terminus. The findings established that CPT I and CPT II are distinct proteins and that inhibitors of CPT I interact within the catalytic domain, not with an associated regulatory component. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8449948" 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="Britton, C. H., Schultz, R. A., Zhang, B., Esser, V., Foster, D. W., McGarry, J. D. <strong>Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.</strong> Proc. Nat. Acad. Sci. 92: 1984-1988, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892212</a>] [<a href="https://doi.org/10.1073/pnas.92.6.1984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7892212">Britton et al. (1995)</a> used the cDNA for rat liver mitochondrial CPT I as a probe to isolate its counterpart from a human liver cDNA library. The predicted 773-amino acid protein shares 86% identity with the rat enzyme. Northern blot analysis detected a 4.7-kb mRNA in human liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892212" 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="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> used the working draft data of the human genome sequence to characterize the organization of the CPT1A gene. They showed the existence of 20 exons, spanning 60 kb of DNA. Two alternate promoters and numerous transcription factor-binding sites were identified within the 5-prime upstream region of the gene. In the 3-prime untranslated region, the major polyA signal was suggested to lie about 2 kb downstream of the stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" 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="#6" class="mim-tip-reference" title="Britton, C. H., Schultz, R. A., Zhang, B., Esser, V., Foster, D. W., McGarry, J. D. <strong>Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.</strong> Proc. Nat. Acad. Sci. 92: 1984-1988, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892212</a>] [<a href="https://doi.org/10.1073/pnas.92.6.1984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7892212">Britton et al. (1995)</a> assigned the human liver CPT1 gene to 11q by testing of oligonucleotide primers specific to upstream and downstream regions of one of the exon-intron junctions in PCRs with DNA from a panel of somatic cell hybrids. One of the somatic cell hybrids that contained only a small portion of chromosome 11 (11q22-q23) gave negative results. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892212" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By fluorescence in situ hybridization, <a href="#5" class="mim-tip-reference" title="Britton, C. H., Mackey, D. W., Esser, V., Foster, D. W., Burns, D. K., Yarnall, D. P., Froguel, P., McGarry, J. D. <strong>Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B).</strong> Genomics 40: 209-211, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9070950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9070950</a>] [<a href="https://doi.org/10.1006/geno.1996.4539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9070950">Britton et al. (1997)</a> mapped the CPT1A gene to chromosome 11q13.1-q13.5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9070950" 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>Major control over the fatty acid oxidation process is exerted at the level of CPT I by virtue of the unique inhibitability of this enzyme by malonyl-CoA. This fuel 'cross talk' was first recognized in the context of hepatic ketogenesis and its regulation and thereafter emerged as a central component of metabolism in a variety of tissues (summary by <a href="#6" class="mim-tip-reference" title="Britton, C. H., Schultz, R. A., Zhang, B., Esser, V., Foster, D. W., McGarry, J. D. <strong>Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.</strong> Proc. Nat. Acad. Sci. 92: 1984-1988, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7892212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7892212</a>] [<a href="https://doi.org/10.1073/pnas.92.6.1984" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7892212">Britton et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7892212" 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>For many years, it was unclear whether or not there were 2 distinct CPT proteins associated with mitochondrial beta-oxidation. <a href="#3" class="mim-tip-reference" title="Bergstrom, J. P., Reitz, R. C. <strong>Studies on carnitine palmitoyl transferase: the similar nature of CPTi (inner form) and CPTo (outer form).</strong> Arch. Biochem. Biophys. 204: 71-78, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7425647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7425647</a>] [<a href="https://doi.org/10.1016/0003-9861(80)90008-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7425647">Bergstrom and Reitz (1980)</a> showed that CPT I and CPT II have similar physical characteristics, including molecular mass and kinetic properties, and that antibodies raised against each enzyme crossreacted with the other. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7425647" 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="#23" class="mim-tip-reference" title="Slama, A., Brivet, M., Boutron, A., Legrand, A., Saudubray, J.-M., Demaugre, F. <strong>Complementation analysis of carnitine palmitoyltransferase I and II defects.</strong> Pediat. Res. 40: 542-546, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8888280/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8888280</a>] [<a href="https://doi.org/10.1203/00006450-199610000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8888280">Slama et al. (1996)</a> demonstrated complementation between cells from CPT I- and CPT II-deficient (<a href="/entry/255110">255110</a>) individuals, indicating that the respective causative mutations of CPT I and CPT II deficiencies reside in distinct genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8888280" 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="Britton, C. H., Mackey, D. W., Esser, V., Foster, D. W., Burns, D. K., Yarnall, D. P., Froguel, P., McGarry, J. D. <strong>Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B).</strong> Genomics 40: 209-211, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9070950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9070950</a>] [<a href="https://doi.org/10.1006/geno.1996.4539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9070950">Britton et al. (1997)</a> established that liver and fibroblast express the same isoform of mitochondrial CPT1, legitimizing the use of fibroblast assays in the differential diagnosis of the 'muscle' (<a href="/entry/255110">255110</a>) and 'hepatic' (<a href="/entry/255120">255120</a>) forms of CPT deficiency. The findings established unequivocally that carnitine palmitoyltransferases I and II are distinct proteins encoded by separate genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9070950" 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 investigate the mechanism by which central metabolism of lipids can modulate energy balance, <a href="#17" class="mim-tip-reference" title="Obici, S., Feng, Z., Arduini, A., Conti, R., Rossetti, L. <strong>Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production.</strong> Nature Med. 9: 756-761, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754501</a>] [<a href="https://doi.org/10.1038/nm873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754501">Obici et al. (2003)</a> selectively reduced lipid oxidation in the hypothalamus. The activity of CPT1 was decreased in rats either by administration of a ribozyme-containing plasmid designed specifically to decrease the expression of this enzyme, or by infusion of pharmacologic inhibitors of its activity into the third cerebral ventricle. Either genetic or biochemical inhibition of hypothalamic CPT1 activity was sufficient to diminish food intake and endogenous glucose production substantially. <a href="#17" class="mim-tip-reference" title="Obici, S., Feng, Z., Arduini, A., Conti, R., Rossetti, L. <strong>Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production.</strong> Nature Med. 9: 756-761, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754501</a>] [<a href="https://doi.org/10.1038/nm873" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754501">Obici et al. (2003)</a> concluded that changes in the rate of lipid oxidation in selective hypothalamic neurons signaled nutrient availability to the hypothalamus, which in turn modulated the exogenous and endogenous inputs of nutrients into the circulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754501" 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="#22" class="mim-tip-reference" title="Schoors, S., Bruning, U., Missiaen, R., Queiroz, K. C. S., Borgers, G., Elia, I., Zecchin, A., Cantelmo, A. R., Christen, S., Goveia, J., Heggermont, W., Godde, L., and 12 others. <strong>Fatty acid carbon is essential for dNTP synthesis in endothelial cells.</strong> Nature 520: 192-197, 2015. Note: Erratum: Nature 526: 144 only, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25830893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25830893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25830893[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/nature14362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25830893">Schoors et al. (2015)</a> reported that endothelial loss of CPT1A, a rate-limiting enzyme of fatty acid oxidation (FAO), causes vascular sprouting defects due to impaired proliferation, not migration, of human and murine endothelial cells. Reduction of FAO in endothelial cells did not cause energy depletion or disturb redox homeostasis, but did impair de novo nucleotide synthesis for DNA replication. Isotope labeling studies in control endothelial cells showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates), and DNA. CPT1A silencing reduced these processes and depleted endothelial cell stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1A-silenced endothelial cells. Finally, <a href="#22" class="mim-tip-reference" title="Schoors, S., Bruning, U., Missiaen, R., Queiroz, K. C. S., Borgers, G., Elia, I., Zecchin, A., Cantelmo, A. R., Christen, S., Goveia, J., Heggermont, W., Godde, L., and 12 others. <strong>Fatty acid carbon is essential for dNTP synthesis in endothelial cells.</strong> Nature 520: 192-197, 2015. Note: Erratum: Nature 526: 144 only, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25830893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25830893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25830893[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/nature14362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25830893">Schoors et al. (2015)</a> found that CPT1 blockade inhibited pathologic ocular angiogenesis in mice, suggesting a novel strategy for blocking angiogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25830893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Wong, B. W., Wang, X., Zecchin, A., Thienpont, B., Cornelissen, I., Kalucka, J., Garcia-Caballero, M., Missiaen, R., Huanh, H., Bruning, U., Blacher, S., Vinckier, S., and 21 others. <strong>The role of fatty acid beta-oxidation in lymphangiogenesis.</strong> Nature 542: 49-54, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28024299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28024299</a>] [<a href="https://doi.org/10.1038/nature21028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28024299">Wong et al. (2017)</a> reported that in transgenic mouse models, lymphatic endothelial cell (LEC)-specific loss of CPT1A, a rate-controlling enzyme in fatty acid beta-oxidation, impairs lymphatic development. LECs use fatty acid beta-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 (<a href="/entry/601546">601546</a>) upregulates CPT1A expression, which increases acetyl-CoA production dependent on fatty acid beta-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 (<a href="/entry/602700">602700</a>) to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1 target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. <a href="#24" class="mim-tip-reference" title="Wong, B. W., Wang, X., Zecchin, A., Thienpont, B., Cornelissen, I., Kalucka, J., Garcia-Caballero, M., Missiaen, R., Huanh, H., Bruning, U., Blacher, S., Vinckier, S., and 21 others. <strong>The role of fatty acid beta-oxidation in lymphangiogenesis.</strong> Nature 542: 49-54, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28024299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28024299</a>] [<a href="https://doi.org/10.1038/nature21028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28024299">Wong et al. (2017)</a> found that blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl-CoA by supplementing acetate rescues this process in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28024299" 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 an infant with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#15" class="mim-tip-reference" title="IJlst, L., Mandel, H., Oostheim, W., Ruiter, J. P. N., Gutman, A., Wanders, R. J. A. <strong>Molecular basis of hepatic carnitine palmitoyltransferase I deficiency.</strong> J. Clin. Invest. 102: 527-531, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9691089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9691089</a>] [<a href="https://doi.org/10.1172/JCI2927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9691089">IJlst et al. (1998)</a> identified a homozygous mutation in the CPT1A gene (<a href="#0001">600528.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9691089" 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="#25" class="mim-tip-reference" title="Yamamoto, S., Kanazawa, M., Ogawa, A., Takayanagi, M., Ohtake, A., Kohono, Y. <strong>Molecular analysis of hepatic carnitine palmitoyltransferase I deficiency: cDNA and genomic DNA analysis of infants presenting with Reye-like illness.</strong> Proceedings of the VIII International Congress Inborn Errors of Metabolism, Cambridge, U.K., September 2000."None>Yamamoto et al. (2000)</a> reported 3 nonsense mutations, 1 missense mutation, and 2 splicing mutations in 4 Japanese patients with CPT IA deficiency.</p><p><a href="#18" class="mim-tip-reference" title="Ogawa, E., Kanazawa, M., Yamamoto, S., Ohtsuka, S., Ogawa, A., Ohtake, A., Takayanagi, M., Kohno, Y. <strong>Expression analysis of two mutations in carnitine palmitoyltransferase IA deficiency.</strong> J. Hum. Genet. 47: 342-347, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12111367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12111367</a>] [<a href="https://doi.org/10.1007/s100380200047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12111367">Ogawa et al. (2002)</a> stated that 19 patients with CPT IA deficiency and 9 CPT1A mutations had been reported. <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> pointed out that while more than 200 families with CPT II deficiencies were known, fewer than 30 families with CPT IA deficiency had been reported prior to their report. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12189492+12111367" 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="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> characterized 6 novel mutations in 4 CPT1A-deficient patients (<a href="#0003">600528.0003</a>-<a href="#0008">600528.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" 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>12 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600528[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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009628" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009628" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009628</a>
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<p><a href="#15" class="mim-tip-reference" title="IJlst, L., Mandel, H., Oostheim, W., Ruiter, J. P. N., Gutman, A., Wanders, R. J. A. <strong>Molecular basis of hepatic carnitine palmitoyltransferase I deficiency.</strong> J. Clin. Invest. 102: 527-531, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9691089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9691089</a>] [<a href="https://doi.org/10.1172/JCI2927" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9691089">IJlst et al. (1998)</a> described homozygosity for an asp454-to-gly (D454G) missense mutation of the CPT1A gene in a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), the offspring of consanguineous parents. She presented at 15 months of age with diarrhea and feeding difficulties. On admission, she was severely hypotonic and lethargic. Physical examination showed hepatomegaly and decreased tendon reflexes. Hypoketotic hypoglycemia was demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9691089" 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 Japanese patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#25" class="mim-tip-reference" title="Yamamoto, S., Kanazawa, M., Ogawa, A., Takayanagi, M., Ohtake, A., Kohono, Y. <strong>Molecular analysis of hepatic carnitine palmitoyltransferase I deficiency: cDNA and genomic DNA analysis of infants presenting with Reye-like illness.</strong> Proceedings of the VIII International Congress Inborn Errors of Metabolism, Cambridge, U.K., September 2000."None>Yamamoto et al. (2000)</a> identified a 1079A-G mutation in the CPT1A gene, resulting in a glu360-to-gly (E360G) substitution. By functional expression studies in SV40 transformed fibroblasts, <a href="#18" class="mim-tip-reference" title="Ogawa, E., Kanazawa, M., Yamamoto, S., Ohtsuka, S., Ogawa, A., Ohtake, A., Takayanagi, M., Kohno, Y. <strong>Expression analysis of two mutations in carnitine palmitoyltransferase IA deficiency.</strong> J. Hum. Genet. 47: 342-347, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12111367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12111367</a>] [<a href="https://doi.org/10.1007/s100380200047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12111367">Ogawa et al. (2002)</a> found that the E360G mutation caused decreased enzyme activity and protein levels, indicating that it is pathogenic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12111367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356774 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356774;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=rs80356774" 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=rs80356774" 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=RCV000009630 OR RCV000790812" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009630, RCV000790812" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009630...</a>
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<p>In a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> identified a homozygous 298C-T substitution in exon 4 of the CPT1A gene, resulting in a gln100-to-ter (Q100X) mutation. The mutation truncated the protein by 671 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" 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 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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">rs80356790 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356790;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=rs80356790" 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=rs80356790" 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=RCV000009632" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009632" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009632</a>
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<p>In a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> identified a 1241C-T substitution in exon 11 of the CPT1A gene, resulting in an ala414-to-val (A414V) mutation. Both the proband and the proband's father were heterozygous for the mutation. The same patient also had a 1493A-G substitution in exon 13 which produced a tyr498-to-cys (Y498C) mutation (<a href="#0005">600528.0005</a>). Both the proband and the proband's mother were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using functional and structural analysis, <a href="#13" class="mim-tip-reference" title="Gobin, S., Thuillier, L., Jogl, G., Faye, A., Tong, L., Chi, M., Bonnefont, J.-P., Girard, J., Prip-Buus, C. <strong>Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.</strong> J. Biol. Chem. 278: 50428-50434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517221</a>] [<a href="https://doi.org/10.1074/jbc.M310130200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517221">Gobin et al. (2003)</a> found that the A414V mutation results in a severe decrease in protein expression (20- to 30-fold lower than wildtype), indicating protein instability, as well as a 98% decrease in catalytic activity of the CPT I enzyme. Modeling studies suggested that the mutation introduces a conformational change in the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14517221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0005 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, TYR498CYS
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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> rs80356791 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356791;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/rs80356791?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=rs80356791" 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=rs80356791" 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=RCV000009633" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009633" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009633</a>
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<p>For discussion of the tyr498-to-cys (Y498C) mutation in the CPT1A gene that was found in compound heterozygous state in a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>) by <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a>, see <a href="#0004">600528.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using functional and structural analysis, <a href="#13" class="mim-tip-reference" title="Gobin, S., Thuillier, L., Jogl, G., Faye, A., Tong, L., Chi, M., Bonnefont, J.-P., Girard, J., Prip-Buus, C. <strong>Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.</strong> J. Biol. Chem. 278: 50428-50434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517221</a>] [<a href="https://doi.org/10.1074/jbc.M310130200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517221">Gobin et al. (2003)</a> found that the Y498C mutation results in slight protein instability and a 3-fold decrease in enzyme activity. The affected residue is located at some distance from the active site of the enzyme and may cause indirect effects via a conformational change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14517221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, 153-BP DEL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356798 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356798;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=rs80356798" 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=rs80356798" 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=RCV000009634" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009634" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009634</a>
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<p>In a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> identified a 153-bp deletion at nucleotide 1876 of the CPT1A gene resulting from a G-to-A substitution at the intron 15 splice acceptor site. The patient's mother was heterozygous for the mutation, which was not detected in the patient's father nor in 20 healthy controls. The mutation deleted 51 amino acids, from codons 626 to 676. The patient also had a 113-bp intronic insertion at nucleotide 1575 of the cDNA (<a href="#0007">600528.0007</a>) resulting from retention of part of intron 13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<strong>.0007 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, 113-BP INS
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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> rs1169875761 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1169875761;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/rs1169875761?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=rs1169875761" 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=rs1169875761" 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=RCV000009631" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009631" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009631</a>
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<p>For discussion of the 113-bp insertion at nucleotide 1575 of the CPT1A gene that was found in compound heterozygous state in a patient with CPT IA deficiency by <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a>, see <a href="#0006">600528.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009635" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009635" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009635</a>
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<p>In a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#12" class="mim-tip-reference" title="Gobin, S., Bonnefont, J.-P., Prip-Buus, C., Mugnier, C., Ferrec, M., Demaugre, F., Saudubray, J.-M., Rostane, H., Djouadi, F., Wilcox, W., Cederbaum, S., Haas, R., Nyhan, W. L., Green, A., Gray, G., Girard, J., Thuillier, L. <strong>Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.</strong> Hum. Genet. 111: 179-189, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12189492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12189492</a>] [<a href="https://doi.org/10.1007/s00439-002-0752-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12189492">Gobin et al. (2002)</a> identified homozygosity for an 8-kb deletion in the CPT1A gene spanning the distal two-thirds of intron 14 to nucleotide 2107 in exon 17. The rearrangement deleted amino acids 581 to 702. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12189492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, GLY709GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28936374 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28936374;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=rs28936374" 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=rs28936374" 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=RCV000009636" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009636" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009636</a>
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<p>In a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>) reported by <a href="#21" class="mim-tip-reference" title="Schaefer, J., Jackson, S., Taroni, F., Swift, P., Turnbull, D. M. <strong>Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency: implications for diagnosis and therapy.</strong> J. Neurol. Neurosurg. Psychiat. 62: 169-176, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048718</a>] [<a href="https://doi.org/10.1136/jnnp.62.2.169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9048718">Schaefer et al. (1997)</a>, <a href="#13" class="mim-tip-reference" title="Gobin, S., Thuillier, L., Jogl, G., Faye, A., Tong, L., Chi, M., Bonnefont, J.-P., Girard, J., Prip-Buus, C. <strong>Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.</strong> J. Biol. Chem. 278: 50428-50434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517221</a>] [<a href="https://doi.org/10.1074/jbc.M310130200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517221">Gobin et al. (2003)</a> identified compound heterozygosity for 2 mutations in the CPT1A gene: a 2126G-A transition, resulting in a gly709-to-glu (G709E) substitution, and a 1-bp deletion (948delG), resulting in a premature termination signal in exon 10 (<a href="#0010">600528.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14517221+9048718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using functional and structural analysis, <a href="#13" class="mim-tip-reference" title="Gobin, S., Thuillier, L., Jogl, G., Faye, A., Tong, L., Chi, M., Bonnefont, J.-P., Girard, J., Prip-Buus, C. <strong>Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.</strong> J. Biol. Chem. 278: 50428-50434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517221</a>] [<a href="https://doi.org/10.1074/jbc.M310130200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517221">Gobin et al. (2003)</a> found that the G709E mutation resulted in significant protein instability and complete loss of enzyme function. The authors suggested that the mutation introduces a bulky and negatively charged group into the hydrophobic core of the enzyme, causing steric repulsions and unfavorable electrostatic interactions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14517221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<strong>.0010 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, 1-BP DEL, 948G
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80356800 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356800;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=rs80356800" 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=rs80356800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009637" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009637" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009637</a>
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<p>For discussion of the 1-bp deletion in the CPT1A gene (948delG) that was found in compound heterozygous state in a patient with CPT IA deficiency (<a href="/entry/255120">255120</a>) by <a href="#13" class="mim-tip-reference" title="Gobin, S., Thuillier, L., Jogl, G., Faye, A., Tong, L., Chi, M., Bonnefont, J.-P., Girard, J., Prip-Buus, C. <strong>Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.</strong> J. Biol. Chem. 278: 50428-50434, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14517221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14517221</a>] [<a href="https://doi.org/10.1074/jbc.M310130200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14517221">Gobin et al. (2003)</a>, see <a href="#0009">600528.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14517221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0011 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</strong>
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CPT1A, GLY710GLU
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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> rs80356780 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356780;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/rs80356780?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=rs80356780" 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=rs80356780" 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=RCV000009638 OR RCV000723829" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009638, RCV000723829" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009638...</a>
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<p>In affected members of a large Hutterite kindred with CPT IA deficiency (<a href="/entry/255120">255120</a>), <a href="#19" class="mim-tip-reference" title="Prip-Buus, C., Thuillier, L., Abadi, N., Prasad, C., Dilling, L., Klasing, J., Demaugre, F., Greenberg, C. R., Haworth, J. C., Droin, V., Kadhom, N., Gobin, S., Kamoun, P., Girard, J., Bonnefont, J.-P. <strong>Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community.</strong> Molec. Genet. Metab. 73: 46-54, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11350182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11350182</a>] [<a href="https://doi.org/10.1006/mgme.2001.3176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11350182">Prip-Buus et al. (2001)</a> identified a homozygous 2129G-A transition in the CPT1A gene, resulting in a gly710-to-glu (G710E) substitution. Expression studies showed that the G710E mutation alters neither mitochondrial targeting nor stability of the protein, but kinetic studies showed that the mutant enzyme is completely catalytically inactive. The authors suspected a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11350182" 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><div class="mim-changed mim-change">.0012 CPT1A POLYMORPHISM</div></strong>
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CPT1A, PRO479LEU (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356779;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs80356779</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> rs80356779 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356779;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/rs80356779?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=rs80356779" 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=rs80356779" 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=RCV000079911 OR RCV000551382 OR RCV000714476 OR RCV000714477 OR RCV003415824 OR RCV004018983" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000079911, RCV000551382, RCV000714476, RCV000714477, RCV003415824, RCV004018983" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000079911...</a>
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<p>The pro479-to-leu (P479L, c.1436C-T, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356779;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs80356779</a>) variant of CPT1A is highly prevalent among indigenous Arctic peoples of Alaska, Canada, Greenland, and northeast Siberia, with the frequency of the variant allele ranging from 0.68 to 0.85. The variant, which results in reduced CPT1A catalytic activity and significantly decreased sensitivity to inhibition by malonyl-CoA, is under positive selection in these populations, one basis for which has been hypothesized to be the traditional diet, which is heavily based on marine mammals and contains high levels of n-3 polyunsaturated fatty acids (n-3 PUFAs) (summary by <a href="#11" class="mim-tip-reference" title="Gessner, B. D., Wood, T., Johnson, M. A., Richards, C. S., Koeller, D. M. <strong>Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.</strong> Genet. Med. 18: 933-939, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26820065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26820065</a>] [<a href="https://doi.org/10.1038/gim.2015.197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26820065">Gessner et al., 2016</a>). The CPT1A gene maps to a region of chromosome 11 that has been associated with control of plasma levels of PUFAs (see <a href="/entry/612795">612795</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26820065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#7" class="mim-tip-reference" title="Brown, N. F., Mullur, R. S., Subramanian, I., Esser, V., Bennett, M. J., Saudubray, J. M., Feigenbaum, A. S., Kobari, J. A., Macleod, P. M., McGarry, J. D., Cohen, J. C. <strong>Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.</strong> J. Lipid Res. 42: 1134-1142, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11441142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11441142</a>]" pmid="11441142">Brown et al. (2001)</a> reported a 44-year-old male (patient 6) with carnitine palmitoyltransferase IA deficiency (<a href="/entry/255120">255120</a>). The patient had an atypical presentation, having been well until the age of 33 years, when he suffered a single episode of muscle cramping following an alcohol binge while logging. He was then well for a further 6 years until he began to experience escalating episodes of muscle cramps. During the 5 years previous to study he had been hospitalized 85 times for this problem. Between episodes he was well. <a href="#7" class="mim-tip-reference" title="Brown, N. F., Mullur, R. S., Subramanian, I., Esser, V., Bennett, M. J., Saudubray, J. M., Feigenbaum, A. S., Kobari, J. A., Macleod, P. M., McGarry, J. D., Cohen, J. C. <strong>Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.</strong> J. Lipid Res. 42: 1134-1142, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11441142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11441142</a>]" pmid="11441142">Brown et al. (2001)</a> detected homozygosity for a c.1436C-T transition in the CPT1A gene that resulted in a pro479-to-leu (P479L) substitution. Assays performed with cultured skin fibroblasts from this patient indicated that this mutation confers partial resistance to the inhibitory effects of malonyl-CoA. CPT II activity in cultured skin fibroblasts was normal, but CPT I activity was markedly diminished (15% of normal controls). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11441142" 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></div>
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<p><a href="#20" class="mim-tip-reference" title="Rajakumar, C., Ban, M. R., Cao, H., Young, T. K., Bjerregaard, P., Hegele, R. A. <strong>Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I.</strong> J. Lipid Res. 50: 1223-1228, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181627</a>] [<a href="https://doi.org/10.1194/jlr.P900001-JLR200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181627">Rajakumar et al. (2009)</a> noted that the patient with atypical presentation reported by <a href="#7" class="mim-tip-reference" title="Brown, N. F., Mullur, R. S., Subramanian, I., Esser, V., Bennett, M. J., Saudubray, J. M., Feigenbaum, A. S., Kobari, J. A., Macleod, P. M., McGarry, J. D., Cohen, J. C. <strong>Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.</strong> J. Lipid Res. 42: 1134-1142, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11441142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11441142</a>]" pmid="11441142">Brown et al. (2001)</a> was a Canadian aboriginal and that the P479L mutation had been identified in other First Nations and Canadian Inuit individuals. In a screen of 1,111 Greenland Inuit, 50 Canadian Inuit, and 285 healthy non-Inuit controls, <a href="#20" class="mim-tip-reference" title="Rajakumar, C., Ban, M. R., Cao, H., Young, T. K., Bjerregaard, P., Hegele, R. A. <strong>Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I.</strong> J. Lipid Res. 50: 1223-1228, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181627</a>] [<a href="https://doi.org/10.1194/jlr.P900001-JLR200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181627">Rajakumar et al. (2009)</a> found that the P479L mutation occurred frequently in the Inuit populations and was absent from controls. Leu479 was the major allele in Greenlanders, with a frequency of 0.73, and was present in Canadian Inuit with a frequency of 0.93. The P479L substitution was associated with elevated plasma HDL and apoA-I levels. The very large number of unaffected homozygotes among the Greenland population, as well as the lack of CPT1A expression in muscle, led <a href="#20" class="mim-tip-reference" title="Rajakumar, C., Ban, M. R., Cao, H., Young, T. K., Bjerregaard, P., Hegele, R. A. <strong>Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I.</strong> J. Lipid Res. 50: 1223-1228, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181627</a>] [<a href="https://doi.org/10.1194/jlr.P900001-JLR200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19181627">Rajakumar et al. (2009)</a> to hypothesize that the symptoms of the original patient were caused by a mutation other than P479L. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19181627+11441142" 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 identify regions harboring candidate genes influencing extreme cold climate adaptation phenotypes, <a href="#8" class="mim-tip-reference" title="Cardona, A., Pagani, L., Antao, T., Lawson, D. J., Eichstaedt, C. A., Yngvadottir, B., Shwe, M. T. T., Wee, J., Romero, I. G., Raj, S., Metspalu, M., Villems, R., Willerslev, E., Tyler-Smith, C., Malyarchuk, B. A., Derenko, M. V., Kivisild, T. <strong>Genome-wide analysis of cold adaptation in indigenous Siberian populations.</strong> PLoS One 9: e98076, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24847810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24847810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24847810[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/10.1371/journal.pone.0098076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24847810">Cardona et al. (2014)</a> genotyped 200 individuals from 10 indigenous Siberian populations for more than 700,000 SNPs and analyzed the results for signals of positive selection. The strongest selection signals mapped to a 3-Mb region on chromosome 11 (chr11:66-69 Mb) that contains the CPT1A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24847810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p>Following up on the work of <a href="#8" class="mim-tip-reference" title="Cardona, A., Pagani, L., Antao, T., Lawson, D. J., Eichstaedt, C. A., Yngvadottir, B., Shwe, M. T. T., Wee, J., Romero, I. G., Raj, S., Metspalu, M., Villems, R., Willerslev, E., Tyler-Smith, C., Malyarchuk, B. A., Derenko, M. V., Kivisild, T. <strong>Genome-wide analysis of cold adaptation in indigenous Siberian populations.</strong> PLoS One 9: e98076, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24847810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24847810</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24847810[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/10.1371/journal.pone.0098076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24847810">Cardona et al. (2014)</a>, <a href="#9" class="mim-tip-reference" title="Clemente, F. J., Cardona, A., Inchley, C. E., Peter, B. M., Jacobs, G., Pagani, L., Lawson, D. J., Antao, T., Vicente, M., Mitt, M., DeGiorgio, M., Faltyskova, Z., and 18 others. <strong>A selective sweep on a deleterious mutation in CPT1A in Arctic populations.</strong> Am. J. Hum. Genet. 95: 584-589, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25449608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25449608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25449608[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/10.1016/j.ajhg.2014.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25449608">Clemente et al. (2014)</a> showed that the P479L variant of CPT1A (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356779;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs80356779</a>, c.1436C-T) is under strong positive selection. They noted that the derived allele is associated with hypoketotic hypoglycemia and high infant mortality, yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in their indigenous northeast Siberian sample, but was absent from other publicly available genomic databases. <a href="#9" class="mim-tip-reference" title="Clemente, F. J., Cardona, A., Inchley, C. E., Peter, B. M., Jacobs, G., Pagani, L., Lawson, D. J., Antao, T., Vicente, M., Mitt, M., DeGiorgio, M., Faltyskova, Z., and 18 others. <strong>A selective sweep on a deleterious mutation in CPT1A in Arctic populations.</strong> Am. J. Hum. Genet. 95: 584-589, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25449608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25449608</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25449608[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/10.1016/j.ajhg.2014.09.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25449608">Clemente et al. (2014)</a> provided evidence of one of the strongest selective sweeps reported in humans, which drove the P479L variant to high frequency in circum-Arctic populations within the last 6,000 to 23,000 years despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment. The traditional diet of indigenous Arctic peoples consists largely of marine mammals and is thus rich in n-3 polyenoic fatty acids, which are known to increase the activity of CPT1A. In this context, a CPT1A activity decrease due to the P479L mutation could be protective against overproduction of ketone bodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25449608+24847810" 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></div>
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<p>In an unmatched case-control study of 110 Alaska Native infants who died before 1 year of age and 395 Alaska Native surviving infants, <a href="#11" class="mim-tip-reference" title="Gessner, B. D., Wood, T., Johnson, M. A., Richards, C. S., Koeller, D. M. <strong>Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.</strong> Genet. Med. 18: 933-939, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26820065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26820065</a>] [<a href="https://doi.org/10.1038/gim.2015.197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26820065">Gessner et al. (2016)</a> found that homozygosity for the P479L variant (which they designated the 'Arctic variant') was associated with infant mortality in all analyses. The overall distribution of genotypes was not significantly different between cases and controls (p = 0.06), but infants who died were more likely to be homozygous for P479L (42% vs 30%). The P479L change results in reduced CPT1A catalytic activity and a significant decrease in sensitivity to inhibition by malonyl-CoA, which is one of the primary mechanisms by which fatty acid oxidation is suppressed when sufficient carbohydrate (glucose) is available for energy production. The traditional diet of populations in which the Arctic variant is found is heavily based on marine mammals and contains high levels of n-3 polyunsaturated fatty acids (n-3 PUFAs). Consumption of such a diet would be predicted to increase expression of CPT1A, reducing the impact of the variant protein's decreased catalytic activity, while the variant's reduction of malonyl-CoA sensitivity would result in increased basal rate of fatty acid oxidation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26820065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="mim-changed mim-change"><p><a href="#1" class="mim-tip-reference" title="Andersen, M. K., Hansen, T. <strong>Genetics of metabolic traits in Greenlanders: lessons from an isolated population.</strong> J. Intern. Med. 284: 464-477, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30101502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30101502</a>] [<a href="https://doi.org/10.1111/joim.12814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30101502">Andersen and Hansen (2018)</a> reviewed the genetics of metabolic traits in Greenlanders and noted that the strongest signal of positive selection reported in Greenlanders and Siberians is the FADS-CPT1A locus on chromosome 11 (PUFAQTL1; <a href="/entry/612795">612795</a>). The T allele of the CPT1A variant P479L (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356779;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs80356779</a>), encoding leu479, is fixed in the ancestral Inuit population, along with the <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs174570;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs174570</a> variant mapping to FADS2, even though approximately 7 Mb separates these 2 variants (<a href="#2" class="mim-tip-reference" title="Andersen, M. K., Jorsboe, E., Sandholt, C. H., Grarup, N., Jorgensen, M. E., Faergeman, N. J., Bjerregaard, P., Pedersen, O., Moltke, I., Hansen, T., Albrechtsen, A. <strong>Identification of novel genetic determinants of erythrocyte membrane fatty acid composition among Greenlanders.</strong> PLoS Genet. 12: e1006119, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27341449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27341449</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27341449[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/10.1371/journal.pgen.1006119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27341449">Andersen et al., 2016</a>). This unusual long-range linkage disequilibrium phenomenon makes it difficult to determine whether the FADS and CPT1A selection signatures represent the same signal or 2 independent signals. However, in Europeans, in whom the P479L variant is monomorphic, a signal of selection has been observed in the FADS locus. <a href="#1" class="mim-tip-reference" title="Andersen, M. K., Hansen, T. <strong>Genetics of metabolic traits in Greenlanders: lessons from an isolated population.</strong> J. Intern. Med. 284: 464-477, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30101502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30101502</a>] [<a href="https://doi.org/10.1111/joim.12814" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30101502">Andersen and Hansen (2018)</a> noted that the Inuit-specific leu479 form of CPT1A had, in cell studies by <a href="#7" class="mim-tip-reference" title="Brown, N. F., Mullur, R. S., Subramanian, I., Esser, V., Bennett, M. J., Saudubray, J. M., Feigenbaum, A. S., Kobari, J. A., Macleod, P. M., McGarry, J. D., Cohen, J. C. <strong>Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.</strong> J. Lipid Res. 42: 1134-1142, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11441142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11441142</a>]" pmid="11441142">Brown et al. (2001)</a> and others, been shown to have markedly reduced enzymatic function, but in combination with reduced sensitivity to malonyl-CoA inhibition. At fasting, this results in moderately reduced beta-oxidation, whereas in the postprandial state the reduced inhibitory sensitivity has a greater impact, as malonyl-CoA concentration is high. Hence, in cell studies, the enzymatic activity of CPT1A has been shown to be 3- to 4-fold higher postprandially in leu479 homozygotes compared to pro479 homozygotes, thereby possibly explaining the background for positive selection at this locus, as increased CPT1A activity favors utilization of fat as an energy source and thereby seems favorable for the Inuit living on a diet rich in fat. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=30101502+11441142+27341449" 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></div>
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<p>In a study to synthesize historical knowledge of the selective sweep of the leu479 form of CPT1A in the Inuit population in the context of updated knowledge of biochemistry, evolutionary genetics, and physiology, <a href="#14" class="mim-tip-reference" title="Hale, N. <strong>Inuit metabolism revisited: what drove the selective sweep of CPT1A L479?</strong> Molec. Genet. Metab. 129: 255-271, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088118</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.01.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32088118">Hale (2020)</a> provided a reassessment of the body of literature on this subject. Based on the data, <a href="#14" class="mim-tip-reference" title="Hale, N. <strong>Inuit metabolism revisited: what drove the selective sweep of CPT1A L479?</strong> Molec. Genet. Metab. 129: 255-271, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088118</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.01.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32088118">Hale (2020)</a> suggested that leu479 permitted favorable glucose conservation in the setting of the low carbohydrate/high protein diet and cold environment of the Inuit population. <a href="#14" class="mim-tip-reference" title="Hale, N. <strong>Inuit metabolism revisited: what drove the selective sweep of CPT1A L479?</strong> Molec. Genet. Metab. 129: 255-271, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32088118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32088118</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.01.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32088118">Hale (2020)</a> theorized that the favorable glucose conservation effects included increased hepatic glycogen synthesis, possibly decreased cerebral glucose consumption secondary to increased ketone bodies, and decreased glucose consumption through brown fat due to increased acylcarnitines available for brown fat metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32088118" 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="#Zierz1985" class="mim-tip-reference" title="Zierz, S., Engel, A. G. <strong>Regulatory properties of a mutant carnitine palmitoyl transferase in human skeletal muscle.</strong> Europ. J. Biochem. 149: 207-214, 1985.">Zierz and Engel (1985)</a>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9691089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9691089</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9691089" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI2927" target="_blank">Full Text</a>]
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<a id="Murthy1987" class="mim-anchor"></a>
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Murthy, M. S. R., Pande, S. V.
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<strong>Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane.</strong>
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[<a href="https://doi.org/10.1073/pnas.84.2.378" target="_blank">Full Text</a>]
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<strong>Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production.</strong>
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[<a href="https://doi.org/10.1038/nm873" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s100380200047" target="_blank">Full Text</a>]
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Prip-Buus, C., Thuillier, L., Abadi, N., Prasad, C., Dilling, L., Klasing, J., Demaugre, F., Greenberg, C. R., Haworth, J. C., Droin, V., Kadhom, N., Gobin, S., Kamoun, P., Girard, J., Bonnefont, J.-P.
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<strong>Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11350182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11350182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11350182" 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.2001.3176" target="_blank">Full Text</a>]
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Rajakumar, C., Ban, M. R., Cao, H., Young, T. K., Bjerregaard, P., Hegele, R. A.
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<strong>Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19181627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19181627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19181627" 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/10.1194/jlr.P900001-JLR200" target="_blank">Full Text</a>]
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Schaefer, J., Jackson, S., Taroni, F., Swift, P., Turnbull, D. M.
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<strong>Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency: implications for diagnosis and therapy.</strong>
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J. Neurol. Neurosurg. Psychiat. 62: 169-176, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9048718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9048718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9048718" 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/10.1136/jnnp.62.2.169" target="_blank">Full Text</a>]
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Schoors, S., Bruning, U., Missiaen, R., Queiroz, K. C. S., Borgers, G., Elia, I., Zecchin, A., Cantelmo, A. R., Christen, S., Goveia, J., Heggermont, W., Godde, L., and 12 others.
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<strong>Fatty acid carbon is essential for dNTP synthesis in endothelial cells.</strong>
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Nature 520: 192-197, 2015. Note: Erratum: Nature 526: 144 only, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25830893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25830893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25830893[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=25830893" 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/nature14362" target="_blank">Full Text</a>]
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Slama, A., Brivet, M., Boutron, A., Legrand, A., Saudubray, J.-M., Demaugre, F.
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<strong>Complementation analysis of carnitine palmitoyltransferase I and II defects.</strong>
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[<a href="https://doi.org/10.1203/00006450-199610000-00005" target="_blank">Full Text</a>]
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Wong, B. W., Wang, X., Zecchin, A., Thienpont, B., Cornelissen, I., Kalucka, J., Garcia-Caballero, M., Missiaen, R., Huanh, H., Bruning, U., Blacher, S., Vinckier, S., and 21 others.
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<strong>The role of fatty acid beta-oxidation in lymphangiogenesis.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28024299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28024299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28024299" 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/nature21028" target="_blank">Full Text</a>]
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Yamamoto, S., Kanazawa, M., Ogawa, A., Takayanagi, M., Ohtake, A., Kohono, Y.
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<strong>Molecular analysis of hepatic carnitine palmitoyltransferase I deficiency: cDNA and genomic DNA analysis of infants presenting with Reye-like illness.</strong>
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<strong>Regulatory properties of a mutant carnitine palmitoyl transferase in human skeletal muscle.</strong>
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Europ. J. Biochem. 149: 207-214, 1985.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3996401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3996401</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3996401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1432-1033.1985.tb08913.x" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 05/27/2020
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Ada Hamosh - updated : 10/26/2018<br>Ada Hamosh - updated : 01/19/2018<br>Ada Hamosh - updated : 7/1/2015<br>Cassandra L. Kniffin - reorganized : 8/23/2004<br>Cassandra L. Kniffin - updated : 8/19/2004<br>Ada Hamosh - updated : 9/15/2003<br>Victor A. McKusick - updated : 10/2/2002<br>Victor A. McKusick - updated : 8/5/2002<br>Victor A. McKusick - updated : 10/1/1998<br>Victor A. McKusick - updated : 3/27/1998<br>Lori M. Kelman - updated : 1/30/1998
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Victor A. McKusick : 5/12/1995
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carol : 05/28/2020<br>carol : 05/27/2020<br>alopez : 10/26/2018<br>alopez : 01/19/2018<br>alopez : 08/12/2016<br>carol : 07/12/2016<br>carol : 6/23/2016<br>mcolton : 8/19/2015<br>alopez : 7/1/2015<br>carol : 1/19/2011<br>terry : 3/22/2006<br>carol : 8/23/2004<br>ckniffin : 8/19/2004<br>cwells : 11/10/2003<br>alopez : 9/15/2003<br>alopez : 9/15/2003<br>alopez : 9/15/2003<br>tkritzer : 10/10/2002<br>tkritzer : 10/4/2002<br>terry : 10/2/2002<br>tkritzer : 8/8/2002<br>tkritzer : 8/7/2002<br>tkritzer : 8/6/2002<br>terry : 8/5/2002<br>alopez : 4/17/2001<br>alopez : 4/17/2001<br>terry : 4/12/2001<br>carol : 10/6/1998<br>terry : 10/1/1998<br>psherman : 3/27/1998<br>dholmes : 3/6/1998<br>dholmes : 1/30/1998<br>dholmes : 1/30/1998<br>dholmes : 1/30/1998<br>mark : 9/11/1997<br>terry : 9/4/1997<br>mark : 7/14/1995<br>mark : 5/12/1995
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CARNITINE PALMITOYLTRANSFERASE I, LIVER; CPT1A
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CPT IA<br />
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CPT I, LIVER<br />
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CPT1
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<strong><em>HGNC Approved Gene Symbol: CPT1A</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>SNOMEDCT:</strong> 238001003;
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</span>
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</p>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 11q13.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 11:68,754,620-68,844,277 </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="1">
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<span class="mim-font">
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11q13.3
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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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CPT deficiency, hepatic, type IA
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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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255120
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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 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>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The CPT1A gene encodes carnitine palmitoyltransferase IA, a liver enzyme involved in fatty acid oxidation. The carnitine palmitoyltransferase (CPT; EC 2.3.1.21) enzyme system, in conjunction with acyl-CoA synthetase and carnitine/acylcarnitine translocase (613698), provides the mechanism whereby long-chain fatty acids are transferred from the cytosol to the mitochondrial matrix to undergo beta-oxidation for energy production. The CPT I isozymes (CPT1A and CPT1B; 601987) are located in the mitochondrial outer membrane and are detergent-labile, whereas CPT II (600650) is located in the inner mitochondrial membrane and is detergent-stable (Bieber, 1988; Murthy and Pande, 1987). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>From a rat liver cDNA library, Esser et al. (1993) isolated a cDNA corresponding to carnitine palmitoyltransferase I. The deduced 773-amino acid protein has a molecular mass of 88 kD. A 4.7-kb mRNA was detected in rat liver. The authors suggested that the de novo synthesized enzyme is targeted to the mitochondrial outer membrane by a leader peptide, and that the mature protein anchors to the membrane through a 20-amino acid region near the N terminus. The findings established that CPT I and CPT II are distinct proteins and that inhibitors of CPT I interact within the catalytic domain, not with an associated regulatory component. </p><p>Britton et al. (1995) used the cDNA for rat liver mitochondrial CPT I as a probe to isolate its counterpart from a human liver cDNA library. The predicted 773-amino acid protein shares 86% identity with the rat enzyme. Northern blot analysis detected a 4.7-kb mRNA in human liver. </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 Structure</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>Gobin et al. (2002) used the working draft data of the human genome sequence to characterize the organization of the CPT1A gene. They showed the existence of 20 exons, spanning 60 kb of DNA. Two alternate promoters and numerous transcription factor-binding sites were identified within the 5-prime upstream region of the gene. In the 3-prime untranslated region, the major polyA signal was suggested to lie about 2 kb downstream of the stop codon. </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>Britton et al. (1995) assigned the human liver CPT1 gene to 11q by testing of oligonucleotide primers specific to upstream and downstream regions of one of the exon-intron junctions in PCRs with DNA from a panel of somatic cell hybrids. One of the somatic cell hybrids that contained only a small portion of chromosome 11 (11q22-q23) gave negative results. </p><p>By fluorescence in situ hybridization, Britton et al. (1997) mapped the CPT1A gene to chromosome 11q13.1-q13.5. </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>Major control over the fatty acid oxidation process is exerted at the level of CPT I by virtue of the unique inhibitability of this enzyme by malonyl-CoA. This fuel 'cross talk' was first recognized in the context of hepatic ketogenesis and its regulation and thereafter emerged as a central component of metabolism in a variety of tissues (summary by Britton et al., 1995). </p><p>For many years, it was unclear whether or not there were 2 distinct CPT proteins associated with mitochondrial beta-oxidation. Bergstrom and Reitz (1980) showed that CPT I and CPT II have similar physical characteristics, including molecular mass and kinetic properties, and that antibodies raised against each enzyme crossreacted with the other. </p><p>Slama et al. (1996) demonstrated complementation between cells from CPT I- and CPT II-deficient (255110) individuals, indicating that the respective causative mutations of CPT I and CPT II deficiencies reside in distinct genes. </p><p>Britton et al. (1997) established that liver and fibroblast express the same isoform of mitochondrial CPT1, legitimizing the use of fibroblast assays in the differential diagnosis of the 'muscle' (255110) and 'hepatic' (255120) forms of CPT deficiency. The findings established unequivocally that carnitine palmitoyltransferases I and II are distinct proteins encoded by separate genes. </p><p>To investigate the mechanism by which central metabolism of lipids can modulate energy balance, Obici et al. (2003) selectively reduced lipid oxidation in the hypothalamus. The activity of CPT1 was decreased in rats either by administration of a ribozyme-containing plasmid designed specifically to decrease the expression of this enzyme, or by infusion of pharmacologic inhibitors of its activity into the third cerebral ventricle. Either genetic or biochemical inhibition of hypothalamic CPT1 activity was sufficient to diminish food intake and endogenous glucose production substantially. Obici et al. (2003) concluded that changes in the rate of lipid oxidation in selective hypothalamic neurons signaled nutrient availability to the hypothalamus, which in turn modulated the exogenous and endogenous inputs of nutrients into the circulation. </p><p>Schoors et al. (2015) reported that endothelial loss of CPT1A, a rate-limiting enzyme of fatty acid oxidation (FAO), causes vascular sprouting defects due to impaired proliferation, not migration, of human and murine endothelial cells. Reduction of FAO in endothelial cells did not cause energy depletion or disturb redox homeostasis, but did impair de novo nucleotide synthesis for DNA replication. Isotope labeling studies in control endothelial cells showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates), and DNA. CPT1A silencing reduced these processes and depleted endothelial cell stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1A-silenced endothelial cells. Finally, Schoors et al. (2015) found that CPT1 blockade inhibited pathologic ocular angiogenesis in mice, suggesting a novel strategy for blocking angiogenesis. </p><p>Wong et al. (2017) reported that in transgenic mouse models, lymphatic endothelial cell (LEC)-specific loss of CPT1A, a rate-controlling enzyme in fatty acid beta-oxidation, impairs lymphatic development. LECs use fatty acid beta-oxidation to proliferate and for epigenetic regulation of lymphatic marker expression during LEC differentiation. Mechanistically, the transcription factor PROX1 (601546) upregulates CPT1A expression, which increases acetyl-CoA production dependent on fatty acid beta-oxidation. Acetyl coenzyme A is used by the histone acetyltransferase p300 (602700) to acetylate histones at lymphangiogenic genes. PROX1-p300 interaction facilitates preferential histone acetylation at PROX1 target genes. Through this metabolism-dependent mechanism, PROX1 mediates epigenetic changes that promote lymphangiogenesis. Wong et al. (2017) found that blockade of CPT1 enzymes inhibits injury-induced lymphangiogenesis, and replenishing acetyl-CoA by supplementing acetate rescues this process in vivo. </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">
|
|
<p>In an infant with CPT IA deficiency (255120), IJlst et al. (1998) identified a homozygous mutation in the CPT1A gene (600528.0001). </p><p>Yamamoto et al. (2000) reported 3 nonsense mutations, 1 missense mutation, and 2 splicing mutations in 4 Japanese patients with CPT IA deficiency.</p><p>Ogawa et al. (2002) stated that 19 patients with CPT IA deficiency and 9 CPT1A mutations had been reported. Gobin et al. (2002) pointed out that while more than 200 families with CPT II deficiencies were known, fewer than 30 families with CPT IA deficiency had been reported prior to their report. </p><p>Gobin et al. (2002) characterized 6 novel mutations in 4 CPT1A-deficient patients (600528.0003-600528.0008). </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
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</span>
|
|
<strong>12 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 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, ASP454GLY
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<br />
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SNP: rs80356778,
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ClinVar: RCV000009628
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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>IJlst et al. (1998) described homozygosity for an asp454-to-gly (D454G) missense mutation of the CPT1A gene in a patient with CPT IA deficiency (255120), the offspring of consanguineous parents. She presented at 15 months of age with diarrhea and feeding difficulties. On admission, she was severely hypotonic and lethargic. Physical examination showed hepatomegaly and decreased tendon reflexes. Hypoketotic hypoglycemia was demonstrated. </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 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, GLU360GLY
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<br />
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SNP: rs80356787,
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ClinVar: RCV000009629
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Japanese patient with CPT IA deficiency (255120), Yamamoto et al. (2000) identified a 1079A-G mutation in the CPT1A gene, resulting in a glu360-to-gly (E360G) substitution. By functional expression studies in SV40 transformed fibroblasts, Ogawa et al. (2002) found that the E360G mutation caused decreased enzyme activity and protein levels, indicating that it is pathogenic. </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 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, GLN100TER
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<br />
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SNP: rs80356774,
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ClinVar: RCV000009630, RCV000790812
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CPT IA deficiency (255120), Gobin et al. (2002) identified a homozygous 298C-T substitution in exon 4 of the CPT1A gene, resulting in a gln100-to-ter (Q100X) mutation. The mutation truncated the protein by 671 amino acids. </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 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, ALA414VAL
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<br />
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SNP: rs80356790,
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ClinVar: RCV000009632
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CPT IA deficiency (255120), Gobin et al. (2002) identified a 1241C-T substitution in exon 11 of the CPT1A gene, resulting in an ala414-to-val (A414V) mutation. Both the proband and the proband's father were heterozygous for the mutation. The same patient also had a 1493A-G substitution in exon 13 which produced a tyr498-to-cys (Y498C) mutation (600528.0005). Both the proband and the proband's mother were heterozygous for the mutation. </p><p>Using functional and structural analysis, Gobin et al. (2003) found that the A414V mutation results in a severe decrease in protein expression (20- to 30-fold lower than wildtype), indicating protein instability, as well as a 98% decrease in catalytic activity of the CPT I enzyme. Modeling studies suggested that the mutation introduces a conformational change in the protein. </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>.0005 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, TYR498CYS
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<br />
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SNP: rs80356791,
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gnomAD: rs80356791,
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ClinVar: RCV000009633
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the tyr498-to-cys (Y498C) mutation in the CPT1A gene that was found in compound heterozygous state in a patient with CPT IA deficiency (255120) by Gobin et al. (2002), see 600528.0004. </p><p>Using functional and structural analysis, Gobin et al. (2003) found that the Y498C mutation results in slight protein instability and a 3-fold decrease in enzyme activity. The affected residue is located at some distance from the active site of the enzyme and may cause indirect effects via a conformational change. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0006 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, 153-BP DEL
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<br />
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SNP: rs80356798,
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ClinVar: RCV000009634
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a patient with CPT IA deficiency (255120), Gobin et al. (2002) identified a 153-bp deletion at nucleotide 1876 of the CPT1A gene resulting from a G-to-A substitution at the intron 15 splice acceptor site. The patient's mother was heterozygous for the mutation, which was not detected in the patient's father nor in 20 healthy controls. The mutation deleted 51 amino acids, from codons 626 to 676. The patient also had a 113-bp intronic insertion at nucleotide 1575 of the cDNA (600528.0007) resulting from retention of part of intron 13. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, 113-BP INS
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<br />
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SNP: rs1169875761,
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gnomAD: rs1169875761,
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ClinVar: RCV000009631
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 113-bp insertion at nucleotide 1575 of the CPT1A gene that was found in compound heterozygous state in a patient with CPT IA deficiency by Gobin et al. (2002), see 600528.0006. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, 8-KB DEL
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<br />
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ClinVar: RCV000009635
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CPT IA deficiency (255120), Gobin et al. (2002) identified homozygosity for an 8-kb deletion in the CPT1A gene spanning the distal two-thirds of intron 14 to nucleotide 2107 in exon 17. The rearrangement deleted amino acids 581 to 702. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0009 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, GLY709GLU
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<br />
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SNP: rs28936374,
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ClinVar: RCV000009636
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with CPT IA deficiency (255120) reported by Schaefer et al. (1997), Gobin et al. (2003) identified compound heterozygosity for 2 mutations in the CPT1A gene: a 2126G-A transition, resulting in a gly709-to-glu (G709E) substitution, and a 1-bp deletion (948delG), resulting in a premature termination signal in exon 10 (600528.0010). </p><p>Using functional and structural analysis, Gobin et al. (2003) found that the G709E mutation resulted in significant protein instability and complete loss of enzyme function. The authors suggested that the mutation introduces a bulky and negatively charged group into the hydrophobic core of the enzyme, causing steric repulsions and unfavorable electrostatic interactions. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0010 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, 1-BP DEL, 948G
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<br />
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SNP: rs80356800,
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ClinVar: RCV000009637
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 1-bp deletion in the CPT1A gene (948delG) that was found in compound heterozygous state in a patient with CPT IA deficiency (255120) by Gobin et al. (2003), see 600528.0009. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0011 CARNITINE PALMITOYLTRANSFERASE IA DEFICIENCY</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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CPT1A, GLY710GLU
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<br />
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SNP: rs80356780,
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gnomAD: rs80356780,
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ClinVar: RCV000009638, RCV000723829
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a large Hutterite kindred with CPT IA deficiency (255120), Prip-Buus et al. (2001) identified a homozygous 2129G-A transition in the CPT1A gene, resulting in a gly710-to-glu (G710E) substitution. Expression studies showed that the G710E mutation alters neither mitochondrial targeting nor stability of the protein, but kinetic studies showed that the mutant enzyme is completely catalytically inactive. The authors suspected a founder effect. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CPT1A POLYMORPHISM</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
CPT1A ARCTIC VARIANT
|
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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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CPT1A, PRO479LEU ({dbSNP rs80356779})
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<br />
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SNP: rs80356779,
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gnomAD: rs80356779,
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ClinVar: RCV000079911, RCV000551382, RCV000714476, RCV000714477, RCV003415824, RCV004018983
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>The pro479-to-leu (P479L, c.1436C-T, rs80356779) variant of CPT1A is highly prevalent among indigenous Arctic peoples of Alaska, Canada, Greenland, and northeast Siberia, with the frequency of the variant allele ranging from 0.68 to 0.85. The variant, which results in reduced CPT1A catalytic activity and significantly decreased sensitivity to inhibition by malonyl-CoA, is under positive selection in these populations, one basis for which has been hypothesized to be the traditional diet, which is heavily based on marine mammals and contains high levels of n-3 polyunsaturated fatty acids (n-3 PUFAs) (summary by Gessner et al., 2016). The CPT1A gene maps to a region of chromosome 11 that has been associated with control of plasma levels of PUFAs (see 612795). </p>
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|
|
<div class="mim-changed mim-change"><p>Brown et al. (2001) reported a 44-year-old male (patient 6) with carnitine palmitoyltransferase IA deficiency (255120). The patient had an atypical presentation, having been well until the age of 33 years, when he suffered a single episode of muscle cramping following an alcohol binge while logging. He was then well for a further 6 years until he began to experience escalating episodes of muscle cramps. During the 5 years previous to study he had been hospitalized 85 times for this problem. Between episodes he was well. Brown et al. (2001) detected homozygosity for a c.1436C-T transition in the CPT1A gene that resulted in a pro479-to-leu (P479L) substitution. Assays performed with cultured skin fibroblasts from this patient indicated that this mutation confers partial resistance to the inhibitory effects of malonyl-CoA. CPT II activity in cultured skin fibroblasts was normal, but CPT I activity was markedly diminished (15% of normal controls). </p></div>
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|
|
<p>Rajakumar et al. (2009) noted that the patient with atypical presentation reported by Brown et al. (2001) was a Canadian aboriginal and that the P479L mutation had been identified in other First Nations and Canadian Inuit individuals. In a screen of 1,111 Greenland Inuit, 50 Canadian Inuit, and 285 healthy non-Inuit controls, Rajakumar et al. (2009) found that the P479L mutation occurred frequently in the Inuit populations and was absent from controls. Leu479 was the major allele in Greenlanders, with a frequency of 0.73, and was present in Canadian Inuit with a frequency of 0.93. The P479L substitution was associated with elevated plasma HDL and apoA-I levels. The very large number of unaffected homozygotes among the Greenland population, as well as the lack of CPT1A expression in muscle, led Rajakumar et al. (2009) to hypothesize that the symptoms of the original patient were caused by a mutation other than P479L. </p>
|
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|
|
<p>To identify regions harboring candidate genes influencing extreme cold climate adaptation phenotypes, Cardona et al. (2014) genotyped 200 individuals from 10 indigenous Siberian populations for more than 700,000 SNPs and analyzed the results for signals of positive selection. The strongest selection signals mapped to a 3-Mb region on chromosome 11 (chr11:66-69 Mb) that contains the CPT1A gene. </p>
|
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|
|
<div class="mim-changed mim-change"><p>Following up on the work of Cardona et al. (2014), Clemente et al. (2014) showed that the P479L variant of CPT1A (rs80356779, c.1436C-T) is under strong positive selection. They noted that the derived allele is associated with hypoketotic hypoglycemia and high infant mortality, yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in their indigenous northeast Siberian sample, but was absent from other publicly available genomic databases. Clemente et al. (2014) provided evidence of one of the strongest selective sweeps reported in humans, which drove the P479L variant to high frequency in circum-Arctic populations within the last 6,000 to 23,000 years despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment. The traditional diet of indigenous Arctic peoples consists largely of marine mammals and is thus rich in n-3 polyenoic fatty acids, which are known to increase the activity of CPT1A. In this context, a CPT1A activity decrease due to the P479L mutation could be protective against overproduction of ketone bodies. </p></div>
|
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|
|
<p>In an unmatched case-control study of 110 Alaska Native infants who died before 1 year of age and 395 Alaska Native surviving infants, Gessner et al. (2016) found that homozygosity for the P479L variant (which they designated the 'Arctic variant') was associated with infant mortality in all analyses. The overall distribution of genotypes was not significantly different between cases and controls (p = 0.06), but infants who died were more likely to be homozygous for P479L (42% vs 30%). The P479L change results in reduced CPT1A catalytic activity and a significant decrease in sensitivity to inhibition by malonyl-CoA, which is one of the primary mechanisms by which fatty acid oxidation is suppressed when sufficient carbohydrate (glucose) is available for energy production. The traditional diet of populations in which the Arctic variant is found is heavily based on marine mammals and contains high levels of n-3 polyunsaturated fatty acids (n-3 PUFAs). Consumption of such a diet would be predicted to increase expression of CPT1A, reducing the impact of the variant protein's decreased catalytic activity, while the variant's reduction of malonyl-CoA sensitivity would result in increased basal rate of fatty acid oxidation. </p>
|
|
|
|
<div class="mim-changed mim-change"><p>Andersen and Hansen (2018) reviewed the genetics of metabolic traits in Greenlanders and noted that the strongest signal of positive selection reported in Greenlanders and Siberians is the FADS-CPT1A locus on chromosome 11 (PUFAQTL1; 612795). The T allele of the CPT1A variant P479L (rs80356779), encoding leu479, is fixed in the ancestral Inuit population, along with the rs174570 variant mapping to FADS2, even though approximately 7 Mb separates these 2 variants (Andersen et al., 2016). This unusual long-range linkage disequilibrium phenomenon makes it difficult to determine whether the FADS and CPT1A selection signatures represent the same signal or 2 independent signals. However, in Europeans, in whom the P479L variant is monomorphic, a signal of selection has been observed in the FADS locus. Andersen and Hansen (2018) noted that the Inuit-specific leu479 form of CPT1A had, in cell studies by Brown et al. (2001) and others, been shown to have markedly reduced enzymatic function, but in combination with reduced sensitivity to malonyl-CoA inhibition. At fasting, this results in moderately reduced beta-oxidation, whereas in the postprandial state the reduced inhibitory sensitivity has a greater impact, as malonyl-CoA concentration is high. Hence, in cell studies, the enzymatic activity of CPT1A has been shown to be 3- to 4-fold higher postprandially in leu479 homozygotes compared to pro479 homozygotes, thereby possibly explaining the background for positive selection at this locus, as increased CPT1A activity favors utilization of fat as an energy source and thereby seems favorable for the Inuit living on a diet rich in fat. </p></div>
|
|
|
|
<p>In a study to synthesize historical knowledge of the selective sweep of the leu479 form of CPT1A in the Inuit population in the context of updated knowledge of biochemistry, evolutionary genetics, and physiology, Hale (2020) provided a reassessment of the body of literature on this subject. Based on the data, Hale (2020) suggested that leu479 permitted favorable glucose conservation in the setting of the low carbohydrate/high protein diet and cold environment of the Inuit population. Hale (2020) theorized that the favorable glucose conservation effects included increased hepatic glycogen synthesis, possibly decreased cerebral glucose consumption secondary to increased ketone bodies, and decreased glucose consumption through brown fat due to increased acylcarnitines available for brown fat metabolism. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Zierz and Engel (1985)
|
|
</span>
|
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Andersen, M. K., Hansen, T.
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<strong>Genetics of metabolic traits in Greenlanders: lessons from an isolated population.</strong>
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J. Intern. Med. 284: 464-477, 2018.
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[PubMed: 30101502]
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[Full Text: https://doi.org/10.1111/joim.12814]
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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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Andersen, M. K., Jorsboe, E., Sandholt, C. H., Grarup, N., Jorgensen, M. E., Faergeman, N. J., Bjerregaard, P., Pedersen, O., Moltke, I., Hansen, T., Albrechtsen, A.
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<strong>Identification of novel genetic determinants of erythrocyte membrane fatty acid composition among Greenlanders.</strong>
|
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PLoS Genet. 12: e1006119, 2016. Note: Electronic Article.
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[PubMed: 27341449]
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[Full Text: https://doi.org/10.1371/journal.pgen.1006119]
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<p class="mim-text-font">
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Bergstrom, J. P., Reitz, R. C.
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<strong>Studies on carnitine palmitoyl transferase: the similar nature of CPTi (inner form) and CPTo (outer form).</strong>
|
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Arch. Biochem. Biophys. 204: 71-78, 1980.
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[PubMed: 7425647]
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[Full Text: https://doi.org/10.1016/0003-9861(80)90008-9]
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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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Bieber, L. L.
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<strong>Carnitine.</strong>
|
|
Annu. Rev. Biochem. 57: 261-283, 1988.
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[PubMed: 3052273]
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[Full Text: https://doi.org/10.1146/annurev.bi.57.070188.001401]
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</p>
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<p class="mim-text-font">
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Britton, C. H., Mackey, D. W., Esser, V., Foster, D. W., Burns, D. K., Yarnall, D. P., Froguel, P., McGarry, J. D.
|
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<strong>Fine chromosome mapping of the genes for human liver and muscle carnitine palmitoyltransferase I (CPT1A and CPT1B).</strong>
|
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Genomics 40: 209-211, 1997.
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[PubMed: 9070950]
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[Full Text: https://doi.org/10.1006/geno.1996.4539]
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<li>
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<p class="mim-text-font">
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Britton, C. H., Schultz, R. A., Zhang, B., Esser, V., Foster, D. W., McGarry, J. D.
|
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<strong>Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.</strong>
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Proc. Nat. Acad. Sci. 92: 1984-1988, 1995.
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[PubMed: 7892212]
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[Full Text: https://doi.org/10.1073/pnas.92.6.1984]
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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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Brown, N. F., Mullur, R. S., Subramanian, I., Esser, V., Bennett, M. J., Saudubray, J. M., Feigenbaum, A. S., Kobari, J. A., Macleod, P. M., McGarry, J. D., Cohen, J. C.
|
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<strong>Molecular characterization of L-CPT I deficiency in six patients: insights into function of the native enzyme.</strong>
|
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J. Lipid Res. 42: 1134-1142, 2001.
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[PubMed: 11441142]
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<li>
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<p class="mim-text-font">
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Cardona, A., Pagani, L., Antao, T., Lawson, D. J., Eichstaedt, C. A., Yngvadottir, B., Shwe, M. T. T., Wee, J., Romero, I. G., Raj, S., Metspalu, M., Villems, R., Willerslev, E., Tyler-Smith, C., Malyarchuk, B. A., Derenko, M. V., Kivisild, T.
|
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<strong>Genome-wide analysis of cold adaptation in indigenous Siberian populations.</strong>
|
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PLoS One 9: e98076, 2014. Note: Electronic Article.
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[PubMed: 24847810]
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[Full Text: https://doi.org/10.1371/journal.pone.0098076]
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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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Clemente, F. J., Cardona, A., Inchley, C. E., Peter, B. M., Jacobs, G., Pagani, L., Lawson, D. J., Antao, T., Vicente, M., Mitt, M., DeGiorgio, M., Faltyskova, Z., and 18 others.
|
|
<strong>A selective sweep on a deleterious mutation in CPT1A in Arctic populations.</strong>
|
|
Am. J. Hum. Genet. 95: 584-589, 2014.
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[PubMed: 25449608]
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[Full Text: https://doi.org/10.1016/j.ajhg.2014.09.016]
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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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Esser, V., Britton, C. H., Weis, B. C., Foster, D. W., McGarry, J. D.
|
|
<strong>Cloning, sequencing, and expression of a cDNA encoding rat liver carnitine palmitoyltransferase I: direct evidence that a single polypeptide is involved in inhibitor interaction and catalytic function.</strong>
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