3901 lines
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Entry
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- *232000 - PROPIONYL-CoA CARBOXYLASE, ALPHA SUBUNIT; PCCA
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- OMIM
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<p>
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<span class="h4">*232000</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/232000">Table View</a>
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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 role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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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=ENSG00000175198;t=ENST00000376285" 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=5095" 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=232000" 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=ENSG00000175198;t=ENST00000376285" 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_000282,NM_001127692,NM_001178004,NM_001352605,NM_001352606,NM_001352607,NM_001352608,NM_001352609,NM_001352610,NM_001352611,NM_001352612,NR_148027,NR_148028,NR_148029,NR_148030,NR_148031,XM_011521093,XM_017020605,XM_017020606,XM_017020607,XM_017020609,XM_017020611,XM_017020612,XM_017020613,XM_017020615,XM_017020616,XM_047430370,XM_047430371,XM_047430372,XM_047430373,XM_047430374,XM_047430375,XM_047430376,XM_047430377,XM_047430378,XR_007063681" 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_000282" 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=232000" 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=01981&isoform_id=01981_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/PCCA" 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/189662,265482,296366,387004,1050988,12652777,18252315,21425221,65506442,119629437,119629438,119629439,189054903,189095269,194383984,194390906,259427632,259453045,259459260,259468948,259475873,259707231,295821183,300538011,300556585,300627562,300628798,300632310,300641453,308153661,767978886,1034584475,1034584477,1034584479,1034584483,1034584487,1034584490,1034584492,1034584498,1034584501,1207996396,1207996400,1207996403,1207996448,1207996478,1207996486,1207996490,1207996511,2217294394,2217294396,2217294401,2217294404,2217294406,2217294409,2217294412,2217294414,2217294416,2462537166,2462537168,2462537170,2462537173,2462537175,2462537177,2462537179,2462537181,2462537185,2462537187,2462537189,2462537191,2462537193,2462537195,2462537197,2462537199,2462537201,2462537203" 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/P05165" 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=5095" 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=ENSG00000175198;t=ENST00000376285" 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=PCCA" 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=PCCA" 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+5095" 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/PCCA" 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:5095" 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/5095" 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=chr13&hgg_gene=ENST00000376285.6&hgg_start=100089093&hgg_end=100530435&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:8653" 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:8653" 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/pcca" 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=232000[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=232000[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/ENSG00000175198" 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=PCCA" 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=PCCA" 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=PCCA" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.uchsc.edu/cbs/pcc/pccmain.htm" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PCCA&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/PA32992" 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:8653" 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://www.mousephenotype.org/data/genes/MGI:97499" 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/PCCA#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:97499" 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/5095/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=5095" 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=WBGene00017864;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-040718-246" 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="mimCellLines">
|
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<span class="panel-title">
|
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:232000" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:5095" 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=PCCA&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> 69080001<br />
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<strong>ICD10CM:</strong> E71.121<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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232000
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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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PROPIONYL-CoA CARBOXYLASE, ALPHA SUBUNIT; PCCA
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</span>
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
pccA COMPLEMENTATION GROUP
|
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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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PCCA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PCCA</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/13/286?start=-3&limit=10&highlight=286">13q32.3</a>
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|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:100089093-100530435&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'})">13:100,089,093-100,530,435</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
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<p>Propionyl-CoA is an important intermediate in the metabolism of several amino acids and is also produced by oxidation of odd-numbered fatty acids. Propionyl-CoA carboxylase (PCC) catalyzes the first step in the catabolism of propionyl-CoA. PCC is composed of 2 nonidentical subunits, alpha and beta. The alpha subunit is encoded by the PCCA gene and the beta subunit by the PCCB gene (<a href="/entry/232050">232050</a>). Cells from patients with propionic acidemia (<a href="/entry/606054">606054</a>) with mutations in the PCCA gene fall into complementation group pccA (summary by <a href="#6" class="mim-tip-reference" title="Fenton, W. A., Gravel, R. A., Rosenblatt, D. S. <strong>Disorders of propionate and methylmalonate metabolism. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001. P. 2176."None>Fenton et al., 2001</a>).</p>
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<p><a href="#15" class="mim-tip-reference" title="Lamhonwah, A. M., Lam, K. F., Tsui, F., Robinson, B., Saunders, M. E., Gravel, R. A. <strong>Assignment of the alpha and beta chains of human propionyl-CoA carboxylase to genetic complementation groups.</strong> Am. J. Hum. Genet. 35: 889-899, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6614005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6614005</a>]" pmid="6614005">Lamhonwah et al. (1983)</a> found that the alpha chain of PCC, which contains the biotin ligand, has a molecular mass of 72 kD; the beta chain, a molecular mass of 56 kD. They predicted that the beta chain is unstable in the absence of the alpha chain. <a href="#15" class="mim-tip-reference" title="Lamhonwah, A. M., Lam, K. F., Tsui, F., Robinson, B., Saunders, M. E., Gravel, R. A. <strong>Assignment of the alpha and beta chains of human propionyl-CoA carboxylase to genetic complementation groups.</strong> Am. J. Hum. Genet. 35: 889-899, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6614005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6614005</a>]" pmid="6614005">Lamhonwah et al. (1983)</a> presented evidence suggesting that the mutation in the pccA complementation group resides in the alpha chain of PCC and that the beta chain is mutant in the pccBC complementation group (which includes subgroups pccB and pccC). Lamhonwah et al. (<a href="#14" class="mim-tip-reference" title="Lamhonwah, A. M., Barankiewicz, T., Willard, H. F., Mahuran, D., Quan, F., Gravel, R. A. <strong>Propionicacidemia: absence of alpha chain mRNA in pccA complementation group. (Abstract)</strong> Am. J. Hum. Genet. 37: A164 only, 1985."None>1985</a>, <a href="#16" class="mim-tip-reference" title="Lamhonwah, A.-M., Barankiewicz, T. J., Willard, H. F., Mahuran, D. J., Quan, F., Gravel, R. A. <strong>Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes.</strong> Proc. Nat. Acad. Sci. 83: 4864-4868, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3460076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3460076</a>] [<a href="https://doi.org/10.1073/pnas.83.13.4864" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3460076">1986</a>) reported that alpha chain mRNA was missing in the pccA complementation group. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6614005+3460076" 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>The family originally reported by <a href="#3" class="mim-tip-reference" title="Childs, B., Nyhan, W. L., Borden, M., Bard, L., Cooke, R. E. <strong>Idiopathic hyperglycinemia and hyperglycinuria: a new disorder of amino acid metabolism.</strong> Pediatrics 27: 522-538, 1961.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13693094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13693094</a>]" pmid="13693094">Childs et al. (1961)</a> had the pccA type of propionic acidemia (<a href="#27" class="mim-tip-reference" title="Wolf, B. <strong>Personal Communication.</strong> Richmond, Va. 1/2/1986."None>Wolf, 1986</a>). Using cDNA clones coding for the alpha and beta chains as probes, <a href="#17" class="mim-tip-reference" title="Lamhonwah, A.-M., Gravel, R. A. <strong>Propionicacidemia: absence of alpha-chain mRNA in fibroblasts from patients of the pccA complementation group.</strong> Am. J. Hum. Genet. 41: 1124-1131, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3687944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3687944</a>]" pmid="3687944">Lamhonwah and Gravel (1987)</a> found absence of alpha mRNA in 4 of 6 pccA strains and the presence of beta mRNA in all pccA mutants studied. They also found the presence of both alpha and beta mRNAs in 3 pccBC, 2 pccB, and 3 pccC mutants. <a href="#20" class="mim-tip-reference" title="Ohura, T., Kraus, J. P., Rosenberg, L. E. <strong>Unequal synthesis and differential degradation of propionyl CoA carboxylase subunits in cells from normal and propionic acidemia patients.</strong> Am. J. Hum. Genet. 45: 33-40, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741949</a>]" pmid="2741949">Ohura et al. (1989)</a> presented evidence from which they concluded that beta-chain subunits of propionyl-CoA carboxylase are normally synthesized and imported into the mitochondria in excess of alpha-chain subunits, but only that portion assembled with alpha subunits escapes degradation. In pccA patients, the primary defect in alpha-chain synthesis leads secondarily to degradation of normally synthesized beta chains. The differential rates of synthesis of alpha and beta chains appear to account for the finding that persons heterozygous for pccBC mutations have normal carboxylase activity in their cells. Among 15 Japanese patients with propionic acidemia, <a href="#21" class="mim-tip-reference" title="Ohura, T., Miyabayashi, S., Narisawa, K., Tada, K. <strong>Genetic heterogeneity of propionic acidemia: analysis of 15 Japanese patients.</strong> Hum. Genet. 87: 41-44, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2037281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2037281</a>] [<a href="https://doi.org/10.1007/BF01213089" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2037281">Ohura et al. (1991)</a> found that both the alpha and beta subunits were absent in 3 and low in 3 others; according to their previous data, they concluded that these 6 patients had an alpha-subunit defect. In 8 other patients, alpha subunits were normal, but the beta subunits were aberrant; these patients were considered to have beta-subunit defects. One of the 15 patients had apparently normal alpha and beta subunits. An altered MspI restriction pattern for PCCB cDNA, consisting of a unique 2.7-kb band, was found in 3 patients with beta-subunit deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2741949+2037281+13693094+3687944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By Southern blot analysis of somatic cell hybrids, <a href="#15" class="mim-tip-reference" title="Lamhonwah, A. M., Lam, K. F., Tsui, F., Robinson, B., Saunders, M. E., Gravel, R. A. <strong>Assignment of the alpha and beta chains of human propionyl-CoA carboxylase to genetic complementation groups.</strong> Am. J. Hum. Genet. 35: 889-899, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6614005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6614005</a>]" pmid="6614005">Lamhonwah et al. (1983)</a> mapped the PCCA gene to chromosome 13. By the study of dosage effect in cell cultures obtained from patients with different deletions of chromosome 13, <a href="#12" class="mim-tip-reference" title="Kennerknecht, I., Suormala, T., Barbi, G., Baumgartner, E. R. <strong>The gene coding for the alpha-chain of human propionyl-CoA carboxylase maps to chromosome band 13q32.</strong> Hum. Genet. 86: 238-240, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2265838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2265838</a>] [<a href="https://doi.org/10.1007/BF00197713" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2265838">Kennerknecht et al. (1990)</a> assigned the PCCA locus to 13q32. By in situ hybridization, <a href="#11" class="mim-tip-reference" title="Kennerknecht, I., Klett, C., Hameister, H. <strong>Assignment of the human gene propionyl coenzyme A carboxylase, alpha-chain, (PCCA) to chromosome 13q32 by in situ hybridization.</strong> Genomics 14: 550-551, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1427880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1427880</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80269-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1427880">Kennerknecht et al. (1992)</a> confirmed the location of PCCA on 13q32. In the CEPH linkage map of human chromosome 13 reported by <a href="#1" class="mim-tip-reference" title="Bowcock, A. M., Gerken, S. C., Barnes, R. I., Shiang, R., Jabs, E. W., Warren, A. C., Antonarakis, S., Retief, A. E., Vergnaud, G., Leppert, M., Lalouel, J.-M., White, R. L., Cavalli-Sforza, L. L. <strong>The CEPH consortium linkage map of human chromosome 13.</strong> Genomics 16: 486-496, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8314586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8314586</a>] [<a href="https://doi.org/10.1006/geno.1993.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8314586">Bowcock et al. (1993)</a>, PCCA was located between D13S92 proximally and D13S60 distally. Using interspecific and intersubspecific mapping panels, <a href="#13" class="mim-tip-reference" title="Koizumi, T., Hendel, E., Lalley, P. A., Tchetgen, M.-B. N., Nadeau, J. H. <strong>Homologs of genes and anonymous loci on human chromosome 13 map to mouse chromosomes 8 and 14.</strong> Mammalian Genome 6: 263-268, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7613031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7613031</a>] [<a href="https://doi.org/10.1007/BF00352413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7613031">Koizumi et al. (1995)</a> mapped the homologous gene to the distal portion of mouse chromosome 14. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6614005+7613031+8314586+1427880+2265838" 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 characterize PCCA gene mutations responsible for PCC deficiency, <a href="#22" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong> Hum. Genet. 101: 93-96, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>] [<a href="https://doi.org/10.1007/s004390050593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385377">Richard et al. (1997)</a> analyzed RT-PCR products obtained from cultured fibroblasts from Spanish PCCA-deficient patients. In 3 patients, smaller than normal PCR products were observed, and sequence analysis revealed deletion of a 54-bp exon in the cDNA. Sequencing of genomic DNA from these 3 patients led to the identification of 3 novel mutations in the PCCA gene, 2 short deletions and 1 small insertion, adjacent to short direct repeats; all of the mutations affected the consensus splice sites of the skipped exon. These mutations (<a href="#0001">232000.0001</a>-<a href="#0003">232000.0003</a>) caused aberrant splicing of the PCCA pre-mRNA and resulted in an in-frame deletion of 54 nucleotides in the cDNA, probably leading to an unstable protein structure that was responsible for the lack of activity resulting in PCC deficiency in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Campeau, E., Dupuis, L., Leclerc, D., Gravel, R. A. <strong>Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene.</strong> Hum. Molec. Genet. 8: 107-113, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887338</a>] [<a href="https://doi.org/10.1093/hmg/8.1.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887338">Campeau et al. (1999)</a> searched for mutations of the PCCA gene using fibroblasts from patients diagnosed with alpha-subunit deficiency. By RT-PCR, 4 of 12 cell lines examined appeared to have a larger transcript present at a level comparable with that of the expected normal species. Sequencing of the larger transcript revealed an 84-bp insertion at nucleotide 1209 of the coding sequence; its incorporation in the transcript resulted in translation termination due to the presence of 2 in-frame stop codons. The 84-bp insertion was found to originate from the intron between nucleotides 1209 and 1210. Consensus splice donor and acceptor sites were found at the 3-prime and 5-prime ends of the insertion, respectively. The insertion was also found in the remaining 8 cell lines as well as in normal cells, but at a much reduced level compared with the normal length sequence. Mutation analysis of the 4 cell lines that showed seemingly elevated levels of the insertion sequence revealed 1 nonsense mutation (arg288 to ter; <a href="#0004">232000.0004</a>), 2 frameshift deletions, and 1 splice mutation as expressed alleles. <a href="#2" class="mim-tip-reference" title="Campeau, E., Dupuis, L., Leclerc, D., Gravel, R. A. <strong>Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene.</strong> Hum. Molec. Genet. 8: 107-113, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887338</a>] [<a href="https://doi.org/10.1093/hmg/8.1.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887338">Campeau et al. (1999)</a> concluded that the common characteristic of the 4 cell lines was that they contained mRNA-destabilizing mutations that reduced the mRNA level of the normal length sequence. Consequently, the low levels of cryptic mRNAs became detectable at a level similar to that of the residual level of the normal length mRNA. They suggested that screening for an increased proportion of the 84-bp insertion by RT-PCR could be used as a rapid assay for RNA-destabilizing mutations. The results suggested caution in associating such mutations with aberrant mRNA species, such as cryptic splice products, which may instead be part of the 'background noise' of the splicing machinery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887338" 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="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects: identification of five novel mutations, one of them causing instability of the protein.</strong> Biochim. Biophys. Acta 1453: 351-358, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10101253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10101253</a>] [<a href="https://doi.org/10.1016/s0925-4439(99)00008-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10101253">Richard et al. (1999)</a> studied the PCCA gene in 12 unrelated propionic acidemia patients with alpha-subunit deficiency, 11 from Spain and 1 from Brazil. A total of 10 different mutations, none predominant, were present in the sample of 24 mutant alleles studied; 5 of these were reported for the first time. One of these mutations, M348K (<a href="#0005">232000.0005</a>), was found to encode an unstable protein, which was probably the disease-causing mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10101253" 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="Ugarte, M., Perez-Cerda, C., Rodriguez-Pombo, P., Desviat, L. R., Perez, B., Richard, E., Muro, S., Campeau, E., Ohura, T., Gravel, R. A. <strong>Overview of mutations in the PCCA and PCCB genes causing propionic acidemia.</strong> Hum. Mutat. 14: 275-282, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502773</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<275::AID-HUMU1>3.0.CO;2-N" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502773">Ugarte et al. (1999)</a> reviewed mutations in the PCCA and PCCB genes. A total of 24 PCCA mutations had been reported, mostly missense point mutations and a variety of splicing defects. No mutation was predominant in the Caucasian or Oriental populations studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502773" 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>Among 10 patients with propionic acidemia, <a href="#5" class="mim-tip-reference" title="Desviat, L. R., Clavero, S., Perez-Cerda, C., Navarrete, R., Ugarte, M., Perez, B. <strong>New splicing mutations in propionic acidemia.</strong> J. Hum. Genet. 51: 992-997, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17051315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17051315</a>] [<a href="https://doi.org/10.1007/s10038-006-0068-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17051315">Desviat et al. (2006)</a> identified 4 different PCCA splice site mutations and 3 different PCCB splice site mutations. The authors emphasized the different molecular effects of splicing mutations and the possible phenotypic consequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17051315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In cultured cells, <a href="#24" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> used antisense morpholino oligonucleotides (AMOs) to restore normal splicing caused by intronic molecular defects in methylmalonic acidemia (<a href="/entry/251000">251000</a>) and propionic acidemia (<a href="/entry/606054">606054</a>). The 3 new point mutations described in deep intronic regions increased the splicing scores of pseudoexons or generated consensus binding motifs for splicing factors, such as SRp40 (<a href="/entry/600914">600914</a>), which favor the intronic inclusions in MUT (1957ins76; <a href="/entry/609058#0013">609058.0013</a>), PCCA (1284ins84; <a href="#0006">232000.0006</a>), or PCCB (654ins72; <a href="/entry/232050#0009">232050.0009</a>) mRNAs. Experimental confirmation that the changes were pathogenic and caused the activation of the pseudoexon was obtained by use of minigenes. AMOs were targeted to the 5-prime or 3-prime cryptic splice sites to block access of a splicing machinery to the pseudoexonic regions of the pre-mRNA. In the PCCA-mutated and PCCB-mutated cell lines, 100% of PCC activity was measured after 24 hours of AMO delivery, and the presence of biotinylated PCCA protein was detected by Western blot in treated PCCA-deficient cells. <a href="#24" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> concluded that this therapeutic strategy would be potentially applicable to a large number of cases with deep intronic changes that, at that time, remained undetected by standard mutation-detection techniques. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17966092" 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="#7" class="mim-tip-reference" title="He, W., Wang, Y., Xie, E. J., Barry, M. A., Zhang, G.-F. <strong>Metabolic perturbations mediated by propionyl-CoA accumulation in organs of mouse model of propionic acidemia.</strong> Molec. Genet. Metab. 134: 257-266, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34635437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34635437</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.09.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34635437">He et al. (2021)</a> investigated propionate and carnitine metabolism in a mouse model with homozygosity for a hypomorphic A138T mutation in the Pcca gene. On a regular diet, the Pcca -/- mice had elevated propionyl carnitine in lung, liver, brain, heart, kidney, and adipose tissue compared to control mice, but had reduced carnitine in only lung and liver compared to the controls. The low carnitine in lung and liver correlated to low acylcarnitines, leading <a href="#7" class="mim-tip-reference" title="He, W., Wang, Y., Xie, E. J., Barry, M. A., Zhang, G.-F. <strong>Metabolic perturbations mediated by propionyl-CoA accumulation in organs of mouse model of propionic acidemia.</strong> Molec. Genet. Metab. 134: 257-266, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34635437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34635437</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.09.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34635437">He et al. (2021)</a> to propose that there was inhibition of fatty acid oxidation in these tissues. To mimic metabolic decompensation, the Pcca -/- mice were acutely administered 13C-labeled propionate. Production of labeled succinate derived from the 13C-labeled propionate was inhibited in some tissues, including brain, lung, liver, kidney and fat, and led to altered citric acid cycle flux. The increased propionate in liver stimulated ketone production from increased fatty acid oxidation, likely due to lowering of malonyl-CoA. Production of labeled succinate from 13C-labeled propionate was not inhibited in heart muscle and pancreas, possibly due to residual PCC activity owing to the hypomorphic nature of the Pcca mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34635437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=232000[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs794727334 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794727334;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=rs794727334" 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=rs794727334" 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=RCV000176154 OR RCV001066663" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000176154, RCV001066663" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000176154...</a>
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<p><a href="#22" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong> Hum. Genet. 101: 93-96, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>] [<a href="https://doi.org/10.1007/s004390050593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385377">Richard et al. (1997)</a> identified a 4-bp (AAGT) deletion in the intron downstream from nucleotide 1824 in the PCCA gene in an 18-year-old patient with a late-onset, relatively mild form of propionic acidemia (<a href="/entry/606054">606054</a>) reported by <a href="#18" class="mim-tip-reference" title="Merinero, B., DelValle, J. A., Jimenez, A., Garcia, M. J., Ugarte, M., Solaguren, R., Lopez, O., Condado, I. <strong>Late onset type of propionic acidaemia: case report and biochemical studies.</strong> J. Inherit. Metab. Dis. 4: 71-72, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6790853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6790853</a>] [<a href="https://doi.org/10.1007/BF02263596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6790853">Merinero et al. (1981)</a>. The diagnosis was made at the age of 17 months. The patient demonstrated a favorable response to restriction of dietary protein, and psychomotor development was adequate. The mutation was present in homozygous form. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6790853+9385377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Clavero, S., Perez, B., Rincon, A., Ugarte, M., Desviat, L. R. <strong>Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes.</strong> Hum. Genet. 115: 239-247, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15235904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15235904</a>] [<a href="https://doi.org/10.1007/s00439-004-1147-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15235904">Clavero et al. (2004)</a> performed mRNA analysis of a fibroblast cell line from the patient reported by <a href="#22" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong> Hum. Genet. 101: 93-96, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>] [<a href="https://doi.org/10.1007/s004390050593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385377">Richard et al. (1997)</a> to test for the presence of normally spliced transcripts which might explain the patient's mild phenotype. Very low levels of normal-sized transcript were detectable by ethidium bromide staining; quantitative RT-PCR revealed 30-fold less correctly spliced PCCA mRNA in the patient's fibroblasts than in normal control fibroblasts. <a href="#4" class="mim-tip-reference" title="Clavero, S., Perez, B., Rincon, A., Ugarte, M., Desviat, L. R. <strong>Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes.</strong> Hum. Genet. 115: 239-247, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15235904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15235904</a>] [<a href="https://doi.org/10.1007/s00439-004-1147-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15235904">Clavero et al. (2004)</a> suggested that very low levels of correctly spliced transcript are sufficient to permit development of the mild phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15235904+9385377" 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="#22" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong> Hum. Genet. 101: 93-96, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>] [<a href="https://doi.org/10.1007/s004390050593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385377">Richard et al. (1997)</a> identified a 9-bp (AGTGTCTTT) deletion in the intron upstream of nucleotide 1771 in the PCCA gene in a 16-year-old patient with a late-onset form of propionic acidemia (<a href="/entry/606054">606054</a>). The diagnosis was made at 6 years of age. Response to restricted dietary protein was favorable, and psychomotor development was adequate. The 9-bp deletion, which affected the invariant AG dinucleotide in the 3-prime splice acceptor site and the first 7 bases of the exon, was present in heterozygous form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385377" 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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PCCA, 2-BP INS, 1824IVS, +3
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2081058900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2081058900;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=rs2081058900" 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=rs2081058900" 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=RCV001293408" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001293408" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001293408</a>
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<p>In a patient with a severe, neonatal form of propionic acidemia (<a href="/entry/606054">606054</a>), which was diagnosed at 2 weeks of age and led to death shortly thereafter, <a href="#22" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong> Hum. Genet. 101: 93-96, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>] [<a href="https://doi.org/10.1007/s004390050593" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9385377">Richard et al. (1997)</a> found a 2-bp (CT) insertion after nucleotide 3 in the intron following coding nucleotide 1824. The mutation was present in heterozygous form and led to an in-frame deletion of 54 nucleotides in the cDNA. The 2-bp insertion in this patient occurred at the same position as the 4-bp deletion (<a href="#0001">232000.0001</a>) that was associated with a late-onset, relatively mild form of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385377" 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 PROPIONIC ACIDEMIA</strong>
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PCCA, ARG288TER
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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> rs121964957 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964957;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/rs121964957?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=rs121964957" 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=rs121964957" 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=RCV000012803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012803</a>
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<p>In cell lines from 2 patients with type I propionic acidemia (<a href="/entry/606054">606054</a>), <a href="#2" class="mim-tip-reference" title="Campeau, E., Dupuis, L., Leclerc, D., Gravel, R. A. <strong>Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene.</strong> Hum. Molec. Genet. 8: 107-113, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887338</a>] [<a href="https://doi.org/10.1093/hmg/8.1.107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887338">Campeau et al. (1999)</a> identified an arg288-to-ter mutation leading to truncation of the PCCA molecule. The underlying mutation, a C-to-T transition at nucleotide 862, was present in homozygous form in 1 patient and in heterozygous form in the second. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887338" 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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PCCA, MET348LYS
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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> rs121964958 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964958;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/rs121964958?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=rs121964958" 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=rs121964958" 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=RCV000012804" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012804" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012804</a>
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<p><a href="#23" class="mim-tip-reference" title="Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M. <strong>Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects: identification of five novel mutations, one of them causing instability of the protein.</strong> Biochim. Biophys. Acta 1453: 351-358, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10101253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10101253</a>] [<a href="https://doi.org/10.1016/s0925-4439(99)00008-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10101253">Richard et al. (1999)</a> found that 2 of 24 PCCA mutant alleles from 12 unrelated patients with propionic acidemia (<a href="/entry/606054">606054</a>) carried a met348-to-lys mutation resulting from a 1043T-A transversion. To examine the effect of the mutation, which involved a highly conserved residue, they carried out in vitro expression of normal and mutant PCCA cDNA. They found that both wildtype and mutant proteins were imported into mitochondria and processed into the mature form with similar efficiency, but the mature mutant M348K protein decayed more rapidly than did the wildtype, indicating a reduced stability, which was probably the disease-causing mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10101253" 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 PROPIONIC ACIDEMIA</strong>
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PCCA, IVS14, A-G, -1416
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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> rs1362195093 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1362195093;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/rs1362195093?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=rs1362195093" 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=rs1362195093" 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=RCV000012805" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012805" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012805</a>
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<p>In cultured cells from a patient with propionic acidemia (<a href="/entry/606054">606054</a>), <a href="#24" class="mim-tip-reference" title="Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B. <strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong> Am. J. Hum. Genet. 81: 1262-1270, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/522376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17966092">Rincon et al. (2007)</a> found a homozygous 84-bp insertion between exons 14 and 15 of PCCA mRNA (1284ins84). The 84-bp insertion corresponded to a pseudoexon in exon 14. The authors amplified the pseudoexon from genomic DNA of the patient and found an A-G substitution (IVS14-1416A-G) in the middle of the inserted sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17966092" 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>See Also:</strong>
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<a href="#Hsia1979" class="mim-tip-reference" title="Hsia, Y. E., Scully, K. J., Rosenberg, L. E. <strong>Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia.</strong> Pediat. Res. 13: 746-751, 1979.">Hsia et al. (1979)</a>; <a href="#Kalousek1983" class="mim-tip-reference" title="Kalousek, F., Orsulak, M. D., Rosenberg, L. R. <strong>Absence of cross-reacting material in isolated propionyl CoA carboxylase deficiency: nature of residual carboxylating activity.</strong> Am. J. Hum. Genet. 35: 409-420, 1983.">Kalousek et al. (1983)</a>; <a href="#Kalousek1980" class="mim-tip-reference" title="Kalousek, T., Darigo, M. C., Rosenberg, L. E. <strong>Isolation and characterization of propionyl-CoA carboxylase from normal human liver: evidence for a protomeric tetramer of nonidentical subunits.</strong> J. Biol. Chem. 255: 60-65, 1980.">Kalousek et al. (1980)</a>; <a href="#Nyhan1961" class="mim-tip-reference" title="Nyhan, W. L., Borden, M., Childs, B. <strong>Idiopathic hyperglycinemia: a new disorder of amino-acids metabolism. II. The concentrations of other amino-acids in the plasma and their modification by the administration of leucine.</strong> Pediatrics 27: 539-550, 1961.">Nyhan et al. (1961)</a>; <a href="#Wolf1980" class="mim-tip-reference" title="Wolf, B., Willard, H. F., Rosenberg, L. E. <strong>Kinetic analysis genetic complementation in heterokaryons of propionyl CoA carboxylase-deficient human fibroblasts.</strong> Am. J. Hum. Genet. 32: 16-25, 1980.">Wolf et al. (1980)</a>
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<strong>REFERENCES</strong>
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Bowcock, A. M., Gerken, S. C., Barnes, R. I., Shiang, R., Jabs, E. W., Warren, A. C., Antonarakis, S., Retief, A. E., Vergnaud, G., Leppert, M., Lalouel, J.-M., White, R. L., Cavalli-Sforza, L. L.
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<strong>The CEPH consortium linkage map of human chromosome 13.</strong>
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Genomics 16: 486-496, 1993.
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[<a href="https://doi.org/10.1006/geno.1993.1215" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/8.1.107" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00439-004-1147-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10038-006-0068-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2021.09.009" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-197906000-00005" target="_blank">Full Text</a>]
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<strong>Assignment of the human gene propionyl coenzyme A carboxylase, alpha-chain, (PCCA) to chromosome 13q32 by in situ hybridization.</strong>
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[<a href="https://doi.org/10.1016/s0888-7543(05)80269-1" target="_blank">Full Text</a>]
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<strong>The gene coding for the alpha-chain of human propionyl-CoA carboxylase maps to chromosome band 13q32.</strong>
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[<a href="https://doi.org/10.1007/BF00197713" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00352413" target="_blank">Full Text</a>]
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<div class="">
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<strong>Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes.</strong>
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[<a href="https://doi.org/10.1073/pnas.83.13.4864" target="_blank">Full Text</a>]
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<strong>Propionicacidemia: absence of alpha-chain mRNA in fibroblasts from patients of the pccA complementation group.</strong>
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[<a href="https://doi.org/10.1007/BF02263596" target="_blank">Full Text</a>]
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<strong>Idiopathic hyperglycinemia: a new disorder of amino-acids metabolism. II. The concentrations of other amino-acids in the plasma and their modification by the administration of leucine.</strong>
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<p class="mim-text-font">
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Ohura, T., Kraus, J. P., Rosenberg, L. E.
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|
<strong>Unequal synthesis and differential degradation of propionyl CoA carboxylase subunits in cells from normal and propionic acidemia patients.</strong>
|
|
Am. J. Hum. Genet. 45: 33-40, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2741949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2741949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2741949" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Ohura1991" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Ohura, T., Miyabayashi, S., Narisawa, K., Tada, K.
|
|
<strong>Genetic heterogeneity of propionic acidemia: analysis of 15 Japanese patients.</strong>
|
|
Hum. Genet. 87: 41-44, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2037281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2037281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2037281" 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/10.1007/BF01213089" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="22" class="mim-anchor"></a>
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<a id="Richard1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M.
|
|
<strong>Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patients.</strong>
|
|
Hum. Genet. 101: 93-96, 1997.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9385377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9385377</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9385377" 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/10.1007/s004390050593" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="23" class="mim-anchor"></a>
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<a id="Richard1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Richard, E., Desviat, L. R., Perez, B., Perez-Cerda, C., Ugarte, M.
|
|
<strong>Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects: identification of five novel mutations, one of them causing instability of the protein.</strong>
|
|
Biochim. Biophys. Acta 1453: 351-358, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10101253/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10101253</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10101253" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0925-4439(99)00008-3" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="24" class="mim-anchor"></a>
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<a id="Rincon2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Rincon, A., Aguado, C., Desviat, L. R., Sanchez-Alcudia, R., Ugarte, M., Perez, B.
|
|
<strong>Propionic and methylmalonic acidemia: antisense therapeutics for intronic variations causing aberrantly spliced messenger RNA.</strong>
|
|
Am. J. Hum. Genet. 81: 1262-1270, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17966092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17966092</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17966092[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=17966092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/522376" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="25" class="mim-anchor"></a>
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<a id="Ugarte1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ugarte, M., Perez-Cerda, C., Rodriguez-Pombo, P., Desviat, L. R., Perez, B., Richard, E., Muro, S., Campeau, E., Ohura, T., Gravel, R. A.
|
|
<strong>Overview of mutations in the PCCA and PCCB genes causing propionic acidemia.</strong>
|
|
Hum. Mutat. 14: 275-282, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502773</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(199910)14:4<275::AID-HUMU1>3.0.CO;2-N" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="26" class="mim-anchor"></a>
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<a id="Wolf1980" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wolf, B., Willard, H. F., Rosenberg, L. E.
|
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<strong>Kinetic analysis genetic complementation in heterokaryons of propionyl CoA carboxylase-deficient human fibroblasts.</strong>
|
|
Am. J. Hum. Genet. 32: 16-25, 1980.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7361761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7361761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7361761" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<li>
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<a id="27" class="mim-anchor"></a>
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<a id="Wolf1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wolf, B.
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<strong>Personal Communication.</strong>
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Richmond, Va. 1/2/1986.
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 12/20/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Victor A. McKusick - updated : 11/28/2007<br>Cassandra L. Kniffin - updated : 3/16/2007<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Ada Hamosh - reorganized : 6/22/2001<br>Victor A. McKusick - updated : 9/5/2000<br>Wilson H. Y. Lo - updated : 11/17/1999<br>Victor A. McKusick - updated : 6/3/1999<br>Victor A. McKusick - updated : 2/18/1999<br>Victor A. McKusick - updated : 9/11/1998<br>Victor A. McKusick - updated : 9/2/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/3/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 11/11/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 12/20/2021<br>carol : 04/23/2020<br>carol : 02/25/2020<br>carol : 10/20/2017<br>carol : 07/15/2016<br>carol : 7/9/2016<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>alopez : 12/11/2007<br>terry : 11/28/2007<br>wwang : 4/2/2007<br>ckniffin : 3/16/2007<br>wwang : 4/27/2005<br>wwang : 4/19/2005<br>terry : 4/18/2005<br>terry : 4/6/2005<br>carol : 9/10/2001<br>carol : 6/22/2001<br>carol : 6/22/2001<br>mcapotos : 9/27/2000<br>mcapotos : 9/19/2000<br>terry : 9/5/2000<br>carol : 4/17/2000<br>carol : 11/22/1999<br>carol : 11/17/1999<br>jlewis : 6/15/1999<br>jlewis : 6/15/1999<br>jlewis : 6/14/1999<br>jlewis : 6/14/1999<br>terry : 6/3/1999<br>mgross : 3/10/1999<br>carol : 2/25/1999<br>mgross : 2/25/1999<br>mgross : 2/22/1999<br>mgross : 2/19/1999<br>terry : 2/18/1999<br>carol : 9/16/1998<br>terry : 9/11/1998<br>alopez : 9/8/1998<br>terry : 9/2/1998<br>mark : 6/15/1995<br>davew : 8/26/1994<br>mimadm : 2/19/1994<br>carol : 9/13/1993<br>carol : 5/26/1993<br>carol : 5/21/1993
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 232000
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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PROPIONYL-CoA CARBOXYLASE, ALPHA SUBUNIT; PCCA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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pccA COMPLEMENTATION GROUP
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PCCA</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> 69080001;
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<strong>ICD10CM:</strong> E71.121;
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</span>
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</p>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 13q32.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:100,089,093-100,530,435 </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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13q32.3
|
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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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Propionicacidemia
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
606054
|
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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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<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">
|
|
<p>Propionyl-CoA is an important intermediate in the metabolism of several amino acids and is also produced by oxidation of odd-numbered fatty acids. Propionyl-CoA carboxylase (PCC) catalyzes the first step in the catabolism of propionyl-CoA. PCC is composed of 2 nonidentical subunits, alpha and beta. The alpha subunit is encoded by the PCCA gene and the beta subunit by the PCCB gene (232050). Cells from patients with propionic acidemia (606054) with mutations in the PCCA gene fall into complementation group pccA (summary by Fenton et al., 2001).</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">
|
|
<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>Lamhonwah et al. (1983) found that the alpha chain of PCC, which contains the biotin ligand, has a molecular mass of 72 kD; the beta chain, a molecular mass of 56 kD. They predicted that the beta chain is unstable in the absence of the alpha chain. Lamhonwah et al. (1983) presented evidence suggesting that the mutation in the pccA complementation group resides in the alpha chain of PCC and that the beta chain is mutant in the pccBC complementation group (which includes subgroups pccB and pccC). Lamhonwah et al. (1985, 1986) reported that alpha chain mRNA was missing in the pccA complementation group. </p><p>The family originally reported by Childs et al. (1961) had the pccA type of propionic acidemia (Wolf, 1986). Using cDNA clones coding for the alpha and beta chains as probes, Lamhonwah and Gravel (1987) found absence of alpha mRNA in 4 of 6 pccA strains and the presence of beta mRNA in all pccA mutants studied. They also found the presence of both alpha and beta mRNAs in 3 pccBC, 2 pccB, and 3 pccC mutants. Ohura et al. (1989) presented evidence from which they concluded that beta-chain subunits of propionyl-CoA carboxylase are normally synthesized and imported into the mitochondria in excess of alpha-chain subunits, but only that portion assembled with alpha subunits escapes degradation. In pccA patients, the primary defect in alpha-chain synthesis leads secondarily to degradation of normally synthesized beta chains. The differential rates of synthesis of alpha and beta chains appear to account for the finding that persons heterozygous for pccBC mutations have normal carboxylase activity in their cells. Among 15 Japanese patients with propionic acidemia, Ohura et al. (1991) found that both the alpha and beta subunits were absent in 3 and low in 3 others; according to their previous data, they concluded that these 6 patients had an alpha-subunit defect. In 8 other patients, alpha subunits were normal, but the beta subunits were aberrant; these patients were considered to have beta-subunit defects. One of the 15 patients had apparently normal alpha and beta subunits. An altered MspI restriction pattern for PCCB cDNA, consisting of a unique 2.7-kb band, was found in 3 patients with beta-subunit deficiency. </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>By Southern blot analysis of somatic cell hybrids, Lamhonwah et al. (1983) mapped the PCCA gene to chromosome 13. By the study of dosage effect in cell cultures obtained from patients with different deletions of chromosome 13, Kennerknecht et al. (1990) assigned the PCCA locus to 13q32. By in situ hybridization, Kennerknecht et al. (1992) confirmed the location of PCCA on 13q32. In the CEPH linkage map of human chromosome 13 reported by Bowcock et al. (1993), PCCA was located between D13S92 proximally and D13S60 distally. Using interspecific and intersubspecific mapping panels, Koizumi et al. (1995) mapped the homologous gene to the distal portion of mouse chromosome 14. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>To characterize PCCA gene mutations responsible for PCC deficiency, Richard et al. (1997) analyzed RT-PCR products obtained from cultured fibroblasts from Spanish PCCA-deficient patients. In 3 patients, smaller than normal PCR products were observed, and sequence analysis revealed deletion of a 54-bp exon in the cDNA. Sequencing of genomic DNA from these 3 patients led to the identification of 3 novel mutations in the PCCA gene, 2 short deletions and 1 small insertion, adjacent to short direct repeats; all of the mutations affected the consensus splice sites of the skipped exon. These mutations (232000.0001-232000.0003) caused aberrant splicing of the PCCA pre-mRNA and resulted in an in-frame deletion of 54 nucleotides in the cDNA, probably leading to an unstable protein structure that was responsible for the lack of activity resulting in PCC deficiency in these patients. </p><p>Campeau et al. (1999) searched for mutations of the PCCA gene using fibroblasts from patients diagnosed with alpha-subunit deficiency. By RT-PCR, 4 of 12 cell lines examined appeared to have a larger transcript present at a level comparable with that of the expected normal species. Sequencing of the larger transcript revealed an 84-bp insertion at nucleotide 1209 of the coding sequence; its incorporation in the transcript resulted in translation termination due to the presence of 2 in-frame stop codons. The 84-bp insertion was found to originate from the intron between nucleotides 1209 and 1210. Consensus splice donor and acceptor sites were found at the 3-prime and 5-prime ends of the insertion, respectively. The insertion was also found in the remaining 8 cell lines as well as in normal cells, but at a much reduced level compared with the normal length sequence. Mutation analysis of the 4 cell lines that showed seemingly elevated levels of the insertion sequence revealed 1 nonsense mutation (arg288 to ter; 232000.0004), 2 frameshift deletions, and 1 splice mutation as expressed alleles. Campeau et al. (1999) concluded that the common characteristic of the 4 cell lines was that they contained mRNA-destabilizing mutations that reduced the mRNA level of the normal length sequence. Consequently, the low levels of cryptic mRNAs became detectable at a level similar to that of the residual level of the normal length mRNA. They suggested that screening for an increased proportion of the 84-bp insertion by RT-PCR could be used as a rapid assay for RNA-destabilizing mutations. The results suggested caution in associating such mutations with aberrant mRNA species, such as cryptic splice products, which may instead be part of the 'background noise' of the splicing machinery. </p><p>Richard et al. (1999) studied the PCCA gene in 12 unrelated propionic acidemia patients with alpha-subunit deficiency, 11 from Spain and 1 from Brazil. A total of 10 different mutations, none predominant, were present in the sample of 24 mutant alleles studied; 5 of these were reported for the first time. One of these mutations, M348K (232000.0005), was found to encode an unstable protein, which was probably the disease-causing mechanism. </p><p>Ugarte et al. (1999) reviewed mutations in the PCCA and PCCB genes. A total of 24 PCCA mutations had been reported, mostly missense point mutations and a variety of splicing defects. No mutation was predominant in the Caucasian or Oriental populations studied. </p><p>Among 10 patients with propionic acidemia, Desviat et al. (2006) identified 4 different PCCA splice site mutations and 3 different PCCB splice site mutations. The authors emphasized the different molecular effects of splicing mutations and the possible phenotypic consequences. </p><p>In cultured cells, Rincon et al. (2007) used antisense morpholino oligonucleotides (AMOs) to restore normal splicing caused by intronic molecular defects in methylmalonic acidemia (251000) and propionic acidemia (606054). The 3 new point mutations described in deep intronic regions increased the splicing scores of pseudoexons or generated consensus binding motifs for splicing factors, such as SRp40 (600914), which favor the intronic inclusions in MUT (1957ins76; 609058.0013), PCCA (1284ins84; 232000.0006), or PCCB (654ins72; 232050.0009) mRNAs. Experimental confirmation that the changes were pathogenic and caused the activation of the pseudoexon was obtained by use of minigenes. AMOs were targeted to the 5-prime or 3-prime cryptic splice sites to block access of a splicing machinery to the pseudoexonic regions of the pre-mRNA. In the PCCA-mutated and PCCB-mutated cell lines, 100% of PCC activity was measured after 24 hours of AMO delivery, and the presence of biotinylated PCCA protein was detected by Western blot in treated PCCA-deficient cells. Rincon et al. (2007) concluded that this therapeutic strategy would be potentially applicable to a large number of cases with deep intronic changes that, at that time, remained undetected by standard mutation-detection techniques. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>He et al. (2021) investigated propionate and carnitine metabolism in a mouse model with homozygosity for a hypomorphic A138T mutation in the Pcca gene. On a regular diet, the Pcca -/- mice had elevated propionyl carnitine in lung, liver, brain, heart, kidney, and adipose tissue compared to control mice, but had reduced carnitine in only lung and liver compared to the controls. The low carnitine in lung and liver correlated to low acylcarnitines, leading He et al. (2021) to propose that there was inhibition of fatty acid oxidation in these tissues. To mimic metabolic decompensation, the Pcca -/- mice were acutely administered 13C-labeled propionate. Production of labeled succinate derived from the 13C-labeled propionate was inhibited in some tissues, including brain, lung, liver, kidney and fat, and led to altered citric acid cycle flux. The increased propionate in liver stimulated ketone production from increased fatty acid oxidation, likely due to lowering of malonyl-CoA. Production of labeled succinate from 13C-labeled propionate was not inhibited in heart muscle and pancreas, possibly due to residual PCC activity owing to the hypomorphic nature of the Pcca mutation. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 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 PROPIONIC ACIDEMIA</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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PCCA, 4-BP DEL, 1824IVS, +3
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<br />
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SNP: rs794727334,
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ClinVar: RCV000176154, RCV001066663
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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>Richard et al. (1997) identified a 4-bp (AAGT) deletion in the intron downstream from nucleotide 1824 in the PCCA gene in an 18-year-old patient with a late-onset, relatively mild form of propionic acidemia (606054) reported by Merinero et al. (1981). The diagnosis was made at the age of 17 months. The patient demonstrated a favorable response to restriction of dietary protein, and psychomotor development was adequate. The mutation was present in homozygous form. </p><p>Clavero et al. (2004) performed mRNA analysis of a fibroblast cell line from the patient reported by Richard et al. (1997) to test for the presence of normally spliced transcripts which might explain the patient's mild phenotype. Very low levels of normal-sized transcript were detectable by ethidium bromide staining; quantitative RT-PCR revealed 30-fold less correctly spliced PCCA mRNA in the patient's fibroblasts than in normal control fibroblasts. Clavero et al. (2004) suggested that very low levels of correctly spliced transcript are sufficient to permit development of the mild phenotype. </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 PROPIONIC ACIDEMIA</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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PCCA, 9-BP DEL, 1771IVS, -2
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<br />
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SNP: rs2152925644,
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ClinVar: RCV000012801
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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>Richard et al. (1997) identified a 9-bp (AGTGTCTTT) deletion in the intron upstream of nucleotide 1771 in the PCCA gene in a 16-year-old patient with a late-onset form of propionic acidemia (606054). The diagnosis was made at 6 years of age. Response to restricted dietary protein was favorable, and psychomotor development was adequate. The 9-bp deletion, which affected the invariant AG dinucleotide in the 3-prime splice acceptor site and the first 7 bases of the exon, was present in heterozygous form. </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 PROPIONIC ACIDEMIA</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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PCCA, 2-BP INS, 1824IVS, +3
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<br />
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SNP: rs2081058900,
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ClinVar: RCV001293408
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a patient with a severe, neonatal form of propionic acidemia (606054), which was diagnosed at 2 weeks of age and led to death shortly thereafter, Richard et al. (1997) found a 2-bp (CT) insertion after nucleotide 3 in the intron following coding nucleotide 1824. The mutation was present in heterozygous form and led to an in-frame deletion of 54 nucleotides in the cDNA. The 2-bp insertion in this patient occurred at the same position as the 4-bp deletion (232000.0001) that was associated with a late-onset, relatively mild form of the disorder. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0004 PROPIONIC ACIDEMIA</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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PCCA, ARG288TER
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<br />
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|
|
SNP: rs121964957,
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|
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gnomAD: rs121964957,
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|
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ClinVar: RCV000012803
|
|
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|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In cell lines from 2 patients with type I propionic acidemia (606054), Campeau et al. (1999) identified an arg288-to-ter mutation leading to truncation of the PCCA molecule. The underlying mutation, a C-to-T transition at nucleotide 862, was present in homozygous form in 1 patient and in heterozygous form in the second. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 PROPIONIC ACIDEMIA</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
PCCA, MET348LYS
|
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|
<br />
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|
|
SNP: rs121964958,
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|
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|
|
|
gnomAD: rs121964958,
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|
|
|
|
|
ClinVar: RCV000012804
|
|
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|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Richard et al. (1999) found that 2 of 24 PCCA mutant alleles from 12 unrelated patients with propionic acidemia (606054) carried a met348-to-lys mutation resulting from a 1043T-A transversion. To examine the effect of the mutation, which involved a highly conserved residue, they carried out in vitro expression of normal and mutant PCCA cDNA. They found that both wildtype and mutant proteins were imported into mitochondria and processed into the mature form with similar efficiency, but the mature mutant M348K protein decayed more rapidly than did the wildtype, indicating a reduced stability, which was probably the disease-causing mechanism. </p>
|
|
</span>
|
|
</div>
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PROPIONIC ACIDEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
PCCA, IVS14, A-G, -1416
|
|
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<br />
|
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|
|
SNP: rs1362195093,
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|
|
gnomAD: rs1362195093,
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ClinVar: RCV000012805
|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In cultured cells from a patient with propionic acidemia (606054), Rincon et al. (2007) found a homozygous 84-bp insertion between exons 14 and 15 of PCCA mRNA (1284ins84). The 84-bp insertion corresponded to a pseudoexon in exon 14. The authors amplified the pseudoexon from genomic DNA of the patient and found an A-G substitution (IVS14-1416A-G) in the middle of the inserted sequence. </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">
|
|
Hsia et al. (1979); Kalousek et al. (1983); Kalousek et al. (1980);
|
|
Nyhan et al. (1961); Wolf et al. (1980)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</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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Bowcock, A. M., Gerken, S. C., Barnes, R. I., Shiang, R., Jabs, E. W., Warren, A. C., Antonarakis, S., Retief, A. E., Vergnaud, G., Leppert, M., Lalouel, J.-M., White, R. L., Cavalli-Sforza, L. L.
|
|
<strong>The CEPH consortium linkage map of human chromosome 13.</strong>
|
|
Genomics 16: 486-496, 1993.
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|
|
[PubMed: 8314586]
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[Full Text: https://doi.org/10.1006/geno.1993.1215]
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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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Campeau, E., Dupuis, L., Leclerc, D., Gravel, R. A.
|
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<strong>Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene.</strong>
|
|
Hum. Molec. Genet. 8: 107-113, 1999.
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[PubMed: 9887338]
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[Full Text: https://doi.org/10.1093/hmg/8.1.107]
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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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Childs, B., Nyhan, W. L., Borden, M., Bard, L., Cooke, R. E.
|
|
<strong>Idiopathic hyperglycinemia and hyperglycinuria: a new disorder of amino acid metabolism.</strong>
|
|
Pediatrics 27: 522-538, 1961.
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[PubMed: 13693094]
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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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Clavero, S., Perez, B., Rincon, A., Ugarte, M., Desviat, L. R.
|
|
<strong>Qualitative and quantitative analysis of the effect of splicing mutations in propionic acidemia underlying non-severe phenotypes.</strong>
|
|
Hum. Genet. 115: 239-247, 2004.
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[PubMed: 15235904]
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[Full Text: https://doi.org/10.1007/s00439-004-1147-1]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Desviat, L. R., Clavero, S., Perez-Cerda, C., Navarrete, R., Ugarte, M., Perez, B.
|
|
<strong>New splicing mutations in propionic acidemia.</strong>
|
|
J. Hum. Genet. 51: 992-997, 2006.
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[PubMed: 17051315]
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[Full Text: https://doi.org/10.1007/s10038-006-0068-3]
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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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</div>
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<div class="modal-footer">
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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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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</body>
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</html>
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