3439 lines
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Entry
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- *607036 - ISOVALERYL-CoA DEHYDROGENASE; IVD
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- OMIM
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<p>
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<span class="h4">*607036</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607036">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 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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<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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<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 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=ENSG00000128928;t=ENST00000487418" 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=3712" 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=607036" 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 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="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</div>
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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=ENSG00000128928;t=ENST00000487418" 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_001159508,NM_001354597,NM_001354598,NM_001354599,NM_001354600,NM_001354601,NM_002225,NR_148925,XM_006720495,XM_017022149,XM_017022153,XM_017022154,XM_017022155,XM_017022157,XM_017022158,XM_047432460,XM_047432461,XM_047432462,XM_047432463,XM_047432464,XR_007064441,XR_007064442" 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_002225" 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=607036" 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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<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=09516&isoform_id=09516_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/IVD" 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/306897,2708700,2708701,6636436,16877964,30583129,60299983,60299985,60299987,119612819,119612820,119612821,189054861,193783817,308219326,578826892,957949650,957949653,957949656,1034590497,1034590506,1034590508,1034590511,1034590517,1034590519,1238812321,1444691830,1444691833,1444691835,1444691837,1444691839,1444691841,1476413338,2217300978,2217300980,2217300987,2217300989,2217300992,2462543908,2462543910,2462543912,2462543915,2462543917,2462543920,2462543922,2462543924,2462543926,2462543928,2462543930,2462543932,2529174392,2529174394" 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/P26440" 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 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=3712" 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=ENSG00000128928;t=ENST00000487418" 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=IVD" 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=IVD" 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+3712" 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/IVD" 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:3712" 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/3712" 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=chr15&hgg_gene=ENST00000487418.8&hgg_start=40405795&hgg_end=40435947&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6186" 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/ivd" 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=607036[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=607036[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/IVD/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000128928" 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=IVD" 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=IVD" 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=IVD" 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.LOVD.nl/IVD" 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=IVD&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/PA29984" 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:6186" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0035911.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1929242" 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/IVD#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:1929242" 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/3712/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=3712" 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=WBGene00015326;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-030616-262" 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:607036" 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:3712" 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=IVD&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> 87827003<br />
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<strong>ICD10CM:</strong> E71.110<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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607036
|
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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>
|
|
<h3>
|
|
<span class="mim-font">
|
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ISOVALERYL-CoA DEHYDROGENASE; IVD
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</span>
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=IVD" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">IVD</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/15/98?start=-3&limit=10&highlight=98">15q15.1</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:40405795-40435947&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'})">15:40,405,795-40,435,947</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
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<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
|
|
|
|
</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">
|
|
<a href="/geneMap/15/98?start=-3&limit=10&highlight=98">
|
|
15q15.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Isovaleric acidemia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/243500"> 243500 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
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<td>
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<p>Isovaleryl-CoA dehydrogenase (<a href="https://enzyme.expasy.org/EC/1.3.99.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.3.99.10</a>) is a member of the acyl-CoA dehydrogenase family and is involved in the catabolism of leucine.</p>
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<p><a href="#5" class="mim-tip-reference" title="Matsubara, Y., Ito, M., Glassberg, R., Satyabhama, S., Ikeda, Y., Tanaka, K. <strong>Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.</strong> J. Clin. Invest. 85: 1058-1064, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2318964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2318964</a>] [<a href="https://doi.org/10.1172/JCI114536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2318964">Matsubara et al. (1990)</a> isolated 5 overlapping IVD cDNA clones from a human placenta cDNA library. The deduced 423-amino acid protein shares 35.8% and 31.6% sequence identity with human short and medium chain acyl-CoA dehydrogenases (<a href="/entry/606885">606885</a>, <a href="/entry/607008">607008</a>), respectively, and 89.6% sequence identity with rat IVD. The leader sequence was determined to be overall positively charged, as is typical of other nuclear-encoded mitochondrial matrix enzymes. The molecular mass of the mature protein is 43 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2318964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By Northern blot analysis of normal human liver and fibroblast poly(A)+ RNA, <a href="#5" class="mim-tip-reference" title="Matsubara, Y., Ito, M., Glassberg, R., Satyabhama, S., Ikeda, Y., Tanaka, K. <strong>Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.</strong> J. Clin. Invest. 85: 1058-1064, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2318964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2318964</a>] [<a href="https://doi.org/10.1172/JCI114536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2318964">Matsubara et al. (1990)</a> found 3 mRNA species of sizes 4.6, 3.8, and 2.1 kb hybridized to IVD cDNA. The 2.1-kb mRNA matched the size of cDNA and was considered to be the translatable species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2318964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Parimoo, B., Tanaka, K. <strong>Structural organization of the human isovaleryl-CoA dehydrogenase gene.</strong> Genomics 15: 582-590, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8468053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8468053</a>] [<a href="https://doi.org/10.1006/geno.1993.1111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8468053">Parimoo and Tanaka (1993)</a> determined that the IVD gene contains 12 exons and has a high GC content upstream of the initiation codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468053" 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="#4" class="mim-tip-reference" title="Kraus, J. P., Matsubara, Y., Barton, D., Yang-Feng, T. L., Glassberg, R., Ito, M., Ikeda, Y., Mole, J., Francke, U., Tanaka, K. <strong>Isolation of cDNA clones coding for rat isovaleryl-CoA dehydrogenase and assignment of the gene to human chromosome 15.</strong> Genomics 1: 264-269, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3446585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3446585</a>] [<a href="https://doi.org/10.1016/0888-7543(87)90053-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3446585">Kraus et al. (1987)</a> used a rat cDNA for IVD in Southern blot analysis of DNAs from human-rodent somatic cell hybrids and in in situ hybridization for localization of the IVD gene to 15q13-q15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3446585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 5 fibroblast lines of different genotypes from patients with isovaleric acidemia (<a href="/entry/243500">243500</a>), <a href="#5" class="mim-tip-reference" title="Matsubara, Y., Ito, M., Glassberg, R., Satyabhama, S., Ikeda, Y., Tanaka, K. <strong>Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.</strong> J. Clin. Invest. 85: 1058-1064, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2318964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2318964</a>] [<a href="https://doi.org/10.1172/JCI114536" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2318964">Matsubara et al. (1990)</a> found 3 mRNA species of similar sizes to normal mRNAs, suggesting that these variants are due in each case to a point mutation or a small deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2318964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> identified 6 classes of patients with IVD deficiency. In size, IVD precursor and mature proteins produced by class I mutants are indistinguishable from their normal counterparts. Class II, III, and IV mutants make IVD precursor proteins 42 kD in size rather than the normal 45 kD. Subsequent processing in class III and IV mutants is normal but proceeds inefficiently in class II mutants. Class V mutants make no detectable IVD protein. Two different missense mutations were identified in class I mutants (<a href="#0001">607036.0001</a>; <a href="#0002">607036.0002</a>). In cDNA from a class III mutant, a single base deletion at position 1179 (<a href="#0003">607036.0003</a>) of the coding region was identified that led to a frameshift, predicting the incorporation of 8 abnormal amino acids followed by a premature termination codon. Sequencing of amplified IVD cDNA from a type V mutant failed to identify any abnormality; the defect might have involved translation of IVD mRNA. <a href="#9" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> identified a transcriptionally defective class of IVD mutant allele (type VI). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" 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="#1" class="mim-tip-reference" title="D'Annibale, O. M., Koppes, E. A., Alodaib, A. N., Kochersperger, C., Karunanidhi, A., Mohsen, A.-W., Vockley, J. <strong>Characterization of variants of uncertain significance in isovaleryl-CoA dehydrogenase identified through newborn screening: an approach for faster analysis.</strong> Molec. Genet. Metab. 134: 29-36, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34535384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34535384</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.08.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34535384">D'Annibale et al. (2021)</a> generated an IVD null HEK293T cell line and transfected the cells with vectors containing IVD cDNA with mutations identified in patients with positive newborn screening for IVA. IVD with an R50P, M329T, R337Q, or c.1179del394 mutation resulted in reduced IVD protein content and activity. IVD with an A311V, T236I, or R411Q mutation resulted in stable IVD protein but no enzyme activity. IVD with a V174G mutation resulted in normal IVD content and activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34535384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), <a href="#2" class="mim-tip-reference" title="Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others. <strong>High-throughput discovery of novel developmental phenotypes.</strong> Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27626380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27626380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27626380[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature19356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27626380">Dickinson et al. (2016)</a> found that knockout of the mouse homolog of human IVD is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27626380" 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=RCV000003743" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003743" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003743</a>
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<p>In a patient with type I isovaleric acidemia (<a href="/entry/243500">243500</a>), <a href="#9" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> demonstrated a change of thymine-125 to cytosine, which was predicted to cause a substitution of proline for leucine at position 13 of the mature IVD protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 ISOVALERIC ACIDEMIA, TYPE I</strong>
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IVD, GLY170VAL
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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> rs121434285 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434285;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/rs121434285?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=rs121434285" 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=rs121434285" 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=RCV000003744 OR RCV000432851 OR RCV000984276 OR RCV003323350" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003744, RCV000432851, RCV000984276, RCV003323350" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003744...</a>
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<p>In a patient with type I IVD deficiency (<a href="/entry/243500">243500</a>), <a href="#9" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> found a change of cytosine-596 to adenine, predicting a substitution of valine for glycine at position 170 of the mature protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span class="mim-font">
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<strong>.0003 ISOVALERIC ACIDEMIA, TYPE III</strong>
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IVD, 1-BP DEL, 1177T
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786204613 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204613;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=rs786204613" 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=rs786204613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000169373 OR RCV000726298 OR RCV002284192" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169373, RCV000726298, RCV002284192" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169373...</a>
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<p>In a patient with type III isovaleric acidemia (<a href="/entry/243500">243500</a>), <a href="#9" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> found deletion of 1 of a triplet of T residues at positions 1177 to 1179. This led to a frameshift that predicted the incorporation of 8 abnormal amino acids followed by a premature termination codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 ISOVALERIC ACIDEMIA, TYPE II</strong>
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IVD, 90-BP DEL, NT145
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000003746" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003746" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003746</a>
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<span class="mim-text-font">
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<p>In cDNA from a patient with type II IVD deficiency (<a href="/entry/243500">243500</a>), <a href="#8" class="mim-tip-reference" title="Vockley, J., Nagao, M., Parimoo, B., Tanaka, K. <strong>The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors.</strong> J. Biol. Chem. 267: 2494-2501, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310317</a>]" pmid="1310317">Vockley et al. (1992)</a> identified a 90-bp deletion encompassing bases 145 to 234. The deletion was caused by an error in RNA splicing and predicted an in-frame deletion of 30 amino acids beginning with leucine-20 of the mature IVD protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 ISOVALERIC ACIDEMIA</strong>
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IVD, IVS7AS, G-A, -1
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555404784 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555404784;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=rs1555404784" 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=rs1555404784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000673634" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000673634" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000673634</a>
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<span class="mim-text-font">
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<p>In fibroblasts from a patient with isovaleric acidemia (<a href="/entry/243500">243500</a>), <a href="#10" class="mim-tip-reference" title="Vockley, J., Rogan, P. K., Anderson, B. D., Willard, J., Seelan, R. S., Smith, D. I., Liu, W. <strong>Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.</strong> Am. J. Hum. Genet. 66: 356-367, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10677295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10677295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10677295[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/10.1086/302751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10677295">Vockley et al. (2000)</a> identified a 15-bp insertion at the 3-prime end of intron 7 of the IVD gene. This missplicing resulted from a G-to-A mutation in the intron 7 acceptor site, altering the AG acceptor to AA. Consequently, a cryptic splice acceptor site in intron 7, located 15 nucleotides upstream of exon 8, was used, accounting for the 15-nucleotide insertion in the cDNA. This insertion maintained the correct reading frame. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10677295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 ISOVALERIC ACIDEMIA</strong>
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IVD, ARG21CYS
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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> rs34695403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs34695403;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/rs34695403?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=rs34695403" 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=rs34695403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000003748" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003748" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003748</a>
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<span class="mim-text-font">
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<p>In fibroblasts from a patient with isovaleric acidemia (<a href="/entry/243500">243500</a>) and skipping of exon 2 of the IVD gene, <a href="#10" class="mim-tip-reference" title="Vockley, J., Rogan, P. K., Anderson, B. D., Willard, J., Seelan, R. S., Smith, D. I., Liu, W. <strong>Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.</strong> Am. J. Hum. Genet. 66: 356-367, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10677295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10677295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10677295[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/10.1086/302751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10677295">Vockley et al. (2000)</a> identified a C-to-T transition at nucleotide 148, resulting in an arg21-to-cys substitution. This mutation involved the same codon mutated in another patient but with a different nucleotide involved. The authors noted that these missense mutations strengthened preexisting cryptic splice acceptors adjacent to the natural splice junctions and apparently interfered with exon recognition, resulting in exon skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10677295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0007 ISOVALERIC ACIDEMIA</strong>
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IVD, ALA282VAL
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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> rs28940889 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28940889;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/rs28940889?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=rs28940889" 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=rs28940889" 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=RCV000003749 OR RCV000080003 OR RCV001266807 OR RCV003952534" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000003749, RCV000080003, RCV001266807, RCV003952534" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000003749...</a>
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<p>By molecular genetic analysis of the IVD gene in 19 subjects in whom isovaleric acidemia (<a href="/entry/243500">243500</a>) was diagnosed through newborn screening by tandem mass spectrometry, <a href="#3" class="mim-tip-reference" title="Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D. <strong>A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.</strong> Am. J. Hum. Genet. 75: 1136-1142, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15486829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15486829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15486829[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/10.1086/426318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15486829">Ensenauer et al. (2004)</a> found that 47% of mutant alleles carried a recurrent mutation, 932C-T (ala282 to val; A282V). Surprisingly, family studies identified 6 healthy older sibs with identical genotype and biochemical evidence of IVA. The findings indicated the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA, which has significant consequences for patient management and counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15486829" 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="#Vockley1989" class="mim-tip-reference" title="Vockley, J., Matsubara, Y., Ikeda, Y., Tanaka, K. <strong>Identification of molecular defects responsible for isovaleric acidemia. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A227 only, 1989.">Vockley et al. (1989)</a>
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<a id="D'Annibale2021" class="mim-anchor"></a>
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D'Annibale, O. M., Koppes, E. A., Alodaib, A. N., Kochersperger, C., Karunanidhi, A., Mohsen, A.-W., Vockley, J.
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<strong>Characterization of variants of uncertain significance in isovaleryl-CoA dehydrogenase identified through newborn screening: an approach for faster analysis.</strong>
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Molec. Genet. Metab. 134: 29-36, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34535384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34535384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34535384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2021.08.012" target="_blank">Full Text</a>]
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Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others.
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<strong>High-throughput discovery of novel developmental phenotypes.</strong>
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Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27626380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27626380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27626380[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=27626380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature19356" target="_blank">Full Text</a>]
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Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D.
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<strong>A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.</strong>
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Am. J. Hum. Genet. 75: 1136-1142, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15486829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15486829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15486829[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=15486829" 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/10.1086/426318" target="_blank">Full Text</a>]
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Kraus, J. P., Matsubara, Y., Barton, D., Yang-Feng, T. L., Glassberg, R., Ito, M., Ikeda, Y., Mole, J., Francke, U., Tanaka, K.
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<strong>Isolation of cDNA clones coding for rat isovaleryl-CoA dehydrogenase and assignment of the gene to human chromosome 15.</strong>
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Genomics 1: 264-269, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3446585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3446585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3446585" 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/10.1016/0888-7543(87)90053-x" target="_blank">Full Text</a>]
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Matsubara, Y., Ito, M., Glassberg, R., Satyabhama, S., Ikeda, Y., Tanaka, K.
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<strong>Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.</strong>
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J. Clin. Invest. 85: 1058-1064, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2318964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2318964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2318964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI114536" target="_blank">Full Text</a>]
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Parimoo, B., Tanaka, K.
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<strong>Structural organization of the human isovaleryl-CoA dehydrogenase gene.</strong>
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Genomics 15: 582-590, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8468053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8468053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1993.1111" target="_blank">Full Text</a>]
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Vockley, J., Matsubara, Y., Ikeda, Y., Tanaka, K.
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<strong>Identification of molecular defects responsible for isovaleric acidemia. (Abstract)</strong>
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Am. J. Hum. Genet. 45 (suppl.): A227 only, 1989.
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Vockley, J., Nagao, M., Parimoo, B., Tanaka, K.
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<strong>The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors.</strong>
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J. Biol. Chem. 267: 2494-2501, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1310317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1310317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1310317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Vockley, J., Parimoo, B., Tanaka, K.
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<strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong>
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Am. J. Hum. Genet. 49: 147-157, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Vockley, J., Rogan, P. K., Anderson, B. D., Willard, J., Seelan, R. S., Smith, D. I., Liu, W.
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<strong>Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.</strong>
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Am. J. Hum. Genet. 66: 356-367, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10677295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10677295</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10677295[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=10677295" 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/10.1086/302751" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 06/23/2022
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Ada Hamosh - updated : 02/16/2017<br>Victor A. McKusick - updated : 11/12/2004
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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 : 02/05/2018<br>alopez : 02/16/2017<br>terry : 04/07/2005<br>carol : 12/9/2004<br>alopez : 11/18/2004<br>terry : 11/12/2004<br>carol : 4/2/2003<br>carol : 7/2/2002<br>ckniffin : 7/2/2002
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 607036
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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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ISOVALERYL-CoA DEHYDROGENASE; IVD
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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-text-font">
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<strong><em>HGNC Approved Gene Symbol: IVD</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> 87827003;
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<strong>ICD10CM:</strong> E71.110;
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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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<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: 15q15.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:40,405,795-40,435,947 </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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15q15.1
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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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Isovaleric acidemia
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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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243500
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Isovaleryl-CoA dehydrogenase (EC 1.3.99.10) is a member of the acyl-CoA dehydrogenase family and is involved in the catabolism of leucine.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Matsubara et al. (1990) isolated 5 overlapping IVD cDNA clones from a human placenta cDNA library. The deduced 423-amino acid protein shares 35.8% and 31.6% sequence identity with human short and medium chain acyl-CoA dehydrogenases (606885, 607008), respectively, and 89.6% sequence identity with rat IVD. The leader sequence was determined to be overall positively charged, as is typical of other nuclear-encoded mitochondrial matrix enzymes. The molecular mass of the mature protein is 43 kD. </p><p>By Northern blot analysis of normal human liver and fibroblast poly(A)+ RNA, Matsubara et al. (1990) found 3 mRNA species of sizes 4.6, 3.8, and 2.1 kb hybridized to IVD cDNA. The 2.1-kb mRNA matched the size of cDNA and was considered to be the translatable species. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Parimoo and Tanaka (1993) determined that the IVD gene contains 12 exons and has a high GC content upstream of the initiation codon. </p>
|
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</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<span class="mim-text-font">
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<p>Kraus et al. (1987) used a rat cDNA for IVD in Southern blot analysis of DNAs from human-rodent somatic cell hybrids and in in situ hybridization for localization of the IVD gene to 15q13-q15. </p>
|
|
</span>
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>In 5 fibroblast lines of different genotypes from patients with isovaleric acidemia (243500), Matsubara et al. (1990) found 3 mRNA species of similar sizes to normal mRNAs, suggesting that these variants are due in each case to a point mutation or a small deletion. </p><p>Vockley et al. (1991) identified 6 classes of patients with IVD deficiency. In size, IVD precursor and mature proteins produced by class I mutants are indistinguishable from their normal counterparts. Class II, III, and IV mutants make IVD precursor proteins 42 kD in size rather than the normal 45 kD. Subsequent processing in class III and IV mutants is normal but proceeds inefficiently in class II mutants. Class V mutants make no detectable IVD protein. Two different missense mutations were identified in class I mutants (607036.0001; 607036.0002). In cDNA from a class III mutant, a single base deletion at position 1179 (607036.0003) of the coding region was identified that led to a frameshift, predicting the incorporation of 8 abnormal amino acids followed by a premature termination codon. Sequencing of amplified IVD cDNA from a type V mutant failed to identify any abnormality; the defect might have involved translation of IVD mRNA. Vockley et al. (1991) identified a transcriptionally defective class of IVD mutant allele (type VI). </p><p>D'Annibale et al. (2021) generated an IVD null HEK293T cell line and transfected the cells with vectors containing IVD cDNA with mutations identified in patients with positive newborn screening for IVA. IVD with an R50P, M329T, R337Q, or c.1179del394 mutation resulted in reduced IVD protein content and activity. IVD with an A311V, T236I, or R411Q mutation resulted in stable IVD protein but no enzyme activity. IVD with a V174G mutation resulted in normal IVD content and activity. </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>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), Dickinson et al. (2016) found that knockout of the mouse homolog of human IVD is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
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|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 ISOVALERIC ACIDEMIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, LEU13PRO
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|
|
|
<br />
|
|
|
|
SNP: rs121434284,
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|
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|
|
ClinVar: RCV000003743
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I isovaleric acidemia (243500), Vockley et al. (1991) demonstrated a change of thymine-125 to cytosine, which was predicted to cause a substitution of proline for leucine at position 13 of the mature IVD protein. </p>
|
|
</span>
|
|
</div>
|
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|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ISOVALERIC ACIDEMIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, GLY170VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434285,
|
|
|
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|
|
gnomAD: rs121434285,
|
|
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|
|
|
ClinVar: RCV000003744, RCV000432851, RCV000984276, RCV003323350
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type I IVD deficiency (243500), Vockley et al. (1991) found a change of cytosine-596 to adenine, predicting a substitution of valine for glycine at position 170 of the mature protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 ISOVALERIC ACIDEMIA, TYPE III</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, 1-BP DEL, 1177T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786204613,
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|
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|
|
|
|
ClinVar: RCV000169373, RCV000726298, RCV002284192
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with type III isovaleric acidemia (243500), Vockley et al. (1991) found deletion of 1 of a triplet of T residues at positions 1177 to 1179. This led to a frameshift that predicted the incorporation of 8 abnormal amino acids followed by a premature termination codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 ISOVALERIC ACIDEMIA, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
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|
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IVD, 90-BP DEL, NT145
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<br />
|
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ClinVar: RCV000003746
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|
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</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In cDNA from a patient with type II IVD deficiency (243500), Vockley et al. (1992) identified a 90-bp deletion encompassing bases 145 to 234. The deletion was caused by an error in RNA splicing and predicted an in-frame deletion of 30 amino acids beginning with leucine-20 of the mature IVD protein. </p>
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 ISOVALERIC ACIDEMIA</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, IVS7AS, G-A, -1
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<br />
|
|
|
|
SNP: rs1555404784,
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|
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|
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ClinVar: RCV000673634
|
|
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</span>
|
|
</div>
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In fibroblasts from a patient with isovaleric acidemia (243500), Vockley et al. (2000) identified a 15-bp insertion at the 3-prime end of intron 7 of the IVD gene. This missplicing resulted from a G-to-A mutation in the intron 7 acceptor site, altering the AG acceptor to AA. Consequently, a cryptic splice acceptor site in intron 7, located 15 nucleotides upstream of exon 8, was used, accounting for the 15-nucleotide insertion in the cDNA. This insertion maintained the correct reading frame. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 ISOVALERIC ACIDEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, ARG21CYS
|
|
|
|
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|
<br />
|
|
|
|
SNP: rs34695403,
|
|
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|
|
|
gnomAD: rs34695403,
|
|
|
|
|
|
ClinVar: RCV000003748
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In fibroblasts from a patient with isovaleric acidemia (243500) and skipping of exon 2 of the IVD gene, Vockley et al. (2000) identified a C-to-T transition at nucleotide 148, resulting in an arg21-to-cys substitution. This mutation involved the same codon mutated in another patient but with a different nucleotide involved. The authors noted that these missense mutations strengthened preexisting cryptic splice acceptors adjacent to the natural splice junctions and apparently interfered with exon recognition, resulting in exon skipping. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ISOVALERIC ACIDEMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
IVD, ALA282VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28940889,
|
|
|
|
|
|
gnomAD: rs28940889,
|
|
|
|
|
|
ClinVar: RCV000003749, RCV000080003, RCV001266807, RCV003952534
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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<p>By molecular genetic analysis of the IVD gene in 19 subjects in whom isovaleric acidemia (243500) was diagnosed through newborn screening by tandem mass spectrometry, Ensenauer et al. (2004) found that 47% of mutant alleles carried a recurrent mutation, 932C-T (ala282 to val; A282V). Surprisingly, family studies identified 6 healthy older sibs with identical genotype and biochemical evidence of IVA. The findings indicated the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA, which has significant consequences for patient management and counseling. </p>
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<strong>See Also:</strong>
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<span class="mim-text-font">
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Vockley et al. (1989)
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<strong>REFERENCES</strong>
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D'Annibale, O. M., Koppes, E. A., Alodaib, A. N., Kochersperger, C., Karunanidhi, A., Mohsen, A.-W., Vockley, J.
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<strong>Characterization of variants of uncertain significance in isovaleryl-CoA dehydrogenase identified through newborn screening: an approach for faster analysis.</strong>
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Molec. Genet. Metab. 134: 29-36, 2021.
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[PubMed: 34535384]
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[Full Text: https://doi.org/10.1016/j.ymgme.2021.08.012]
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Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others.
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<strong>High-throughput discovery of novel developmental phenotypes.</strong>
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Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017.
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[PubMed: 27626380]
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[Full Text: https://doi.org/10.1038/nature19356]
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Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D.
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<strong>A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.</strong>
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Am. J. Hum. Genet. 75: 1136-1142, 2004.
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[PubMed: 15486829]
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[Full Text: https://doi.org/10.1086/426318]
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Kraus, J. P., Matsubara, Y., Barton, D., Yang-Feng, T. L., Glassberg, R., Ito, M., Ikeda, Y., Mole, J., Francke, U., Tanaka, K.
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<strong>Isolation of cDNA clones coding for rat isovaleryl-CoA dehydrogenase and assignment of the gene to human chromosome 15.</strong>
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Genomics 1: 264-269, 1987.
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[PubMed: 3446585]
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[Full Text: https://doi.org/10.1016/0888-7543(87)90053-x]
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Matsubara, Y., Ito, M., Glassberg, R., Satyabhama, S., Ikeda, Y., Tanaka, K.
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<strong>Nucleotide sequence of messenger RNA encoding human isovaleryl-coenzyme A dehydrogenase and its expression in isovaleric acidemia fibroblasts.</strong>
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J. Clin. Invest. 85: 1058-1064, 1990.
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[PubMed: 2318964]
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[Full Text: https://doi.org/10.1172/JCI114536]
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Parimoo, B., Tanaka, K.
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<strong>Structural organization of the human isovaleryl-CoA dehydrogenase gene.</strong>
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Genomics 15: 582-590, 1993.
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[PubMed: 8468053]
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[Full Text: https://doi.org/10.1006/geno.1993.1111]
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Vockley, J., Matsubara, Y., Ikeda, Y., Tanaka, K.
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<strong>Identification of molecular defects responsible for isovaleric acidemia. (Abstract)</strong>
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Am. J. Hum. Genet. 45 (suppl.): A227 only, 1989.
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Vockley, J., Nagao, M., Parimoo, B., Tanaka, K.
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<strong>The variant human isovaleryl-CoA dehydrogenase gene responsible for type II isovaleric acidemia determines an RNA splicing error, leading to the deletion of the entire second coding exon and the production of a truncated precursor protein that interacts poorly with mitochondrial import receptors.</strong>
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J. Biol. Chem. 267: 2494-2501, 1992.
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[PubMed: 1310317]
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Vockley, J., Parimoo, B., Tanaka, K.
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<strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong>
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Am. J. Hum. Genet. 49: 147-157, 1991.
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[PubMed: 2063866]
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Vockley, J., Rogan, P. K., Anderson, B. D., Willard, J., Seelan, R. S., Smith, D. I., Liu, W.
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<strong>Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.</strong>
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Am. J. Hum. Genet. 66: 356-367, 2000.
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[PubMed: 10677295]
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[Full Text: https://doi.org/10.1086/302751]
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Hilary J. Vernon - updated : 06/23/2022<br>Ada Hamosh - updated : 02/16/2017<br>Victor A. McKusick - updated : 11/12/2004
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