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Entry
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- *615317 - IRON-SULFUR CLUSTER ASSEMBLY 2; ISCA2
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- OMIM
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<p>
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<span class="h4">*615317</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="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/615317">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<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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<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 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=ENSG00000165898;t=ENST00000556816" 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=122961" 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=615317" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="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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<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=ENSG00000165898;t=ENST00000556816" 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_001272007,NM_194279" 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_194279" 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=615317" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.proteinatlas.org/search/ISCA2" 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/23273089,28207853,54035057,119601585,119601586,125950361,158254892,160420328,432134254" 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/Q86U28" 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=122961" 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=ENSG00000165898;t=ENST00000556816" 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=ISCA2" 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=ISCA2" 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+122961" 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/ISCA2" 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:122961" 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/122961" 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=chr14&hgg_gene=ENST00000556816.6&hgg_start=74493765&hgg_end=74497106&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:19857" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615317[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=615317[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000165898" 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=ISCA2" 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=ISCA2" 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=ISCA2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ISCA2&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/PA162392315" 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:19857" 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/FBgn0039205.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:1921566" 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/ISCA2#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:1921566" 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/122961/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=122961" 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=WBGene00013218;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-131121-486" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=ISCA2&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> 1208621008<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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615317
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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IRON-SULFUR CLUSTER ASSEMBLY 2; ISCA2
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
IRON-SULFUR CLUSTER ASSEMBLY 2, S. CEREVISIAE, HOMOLOG OF
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</span>
|
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</h4>
|
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</div>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ISCA2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ISCA2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/14/387?start=-3&limit=10&highlight=387">14q24.3</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:74493765-74497106&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'})">14:74,493,765-74,497,106</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
<a href="/geneMap/14/387?start=-3&limit=10&highlight=387">
|
|
14q24.3
|
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</a>
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
|
Multiple mitochondrial dysfunctions syndrome 4
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/616370"> 616370 </a>
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
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|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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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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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/615317" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/615317" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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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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<div id="mimDescriptionFold" class="collapse in ">
|
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<span class="mim-text-font">
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<p>ISCA2, like ISCA1 (<a href="/entry/611006">611006</a>) and IBA57 (<a href="/entry/615316">615316</a>), is part of the iron-sulfur cluster (ISC) assembly machinery in mitochondria. These 3 proteins function late in the biosynthetic pathway of mitochondrial 4Fe-4S proteins (<a href="#5" class="mim-tip-reference" title="Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R. <strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong> Molec. Biol. Cell 23: 1157-1166, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323289</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323289[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/10.1091/mbc.E11-09-0772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22323289">Sheftel et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using cell fractionation, immunoblot analysis, and confocal microscopy, <a href="#5" class="mim-tip-reference" title="Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R. <strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong> Molec. Biol. Cell 23: 1157-1166, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323289</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323289[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/10.1091/mbc.E11-09-0772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22323289">Sheftel et al. (2012)</a> demonstrated mitochondrial localization of human ISCA2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323289" 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="#5" class="mim-tip-reference" title="Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R. <strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong> Molec. Biol. Cell 23: 1157-1166, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323289</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323289[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/10.1091/mbc.E11-09-0772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22323289">Sheftel et al. (2012)</a> used RNA interference to deplete HeLa cells of ISCA1, ISCA2, and IBA57 and observed swollen mitochondria devoid of cristae membranes. Depletion of these proteins also resulted in diminished activities of mitochondrial 4Fe-4S proteins, including aconitase (ACO2; <a href="/entry/100850">100850</a>), respiratory complex I (see <a href="/entry/602985">602985</a>), and lipoic acid synthase (LIAS; <a href="/entry/607031">607031</a>). In contrast, cellular heme content and mitochondrial 2Fe-2S ferrochelatase (FECH; <a href="/entry/612386">612386</a>) were unaffected. <a href="#5" class="mim-tip-reference" title="Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R. <strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong> Molec. Biol. Cell 23: 1157-1166, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323289</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323289[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/10.1091/mbc.E11-09-0772" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22323289">Sheftel et al. (2012)</a> proposed that ISCA1, ISCA2, and IBA57 are specifically involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the ISC assembly pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22323289" 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 6 patients from 5 consanguineous Arab families with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; <a href="/entry/616370">616370</a>), <a href="#1" class="mim-tip-reference" title="Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others. <strong>ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.</strong> J. Med. Genet. 52: 186-194, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25539947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25539947</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25539947">Al-Hassnan et al. (2015)</a> identified a homozygous missense mutation in the ISCA2 gene (G77S; <a href="#0001">615317.0001</a>). The mutation, which was found by a combination of autozygosity mapping and exome sequencing, segregated with the disorder in the families. Haplotype analysis indicated a founder effect. Patient cells showed decreased expression of ISCA2, ISCA1 (<a href="/entry/611006">611006</a>), and IBA57 (<a href="/entry/615316">615316</a>). Functional studies of the ISCA2 variant were not performed, but <a href="#1" class="mim-tip-reference" title="Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others. <strong>ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.</strong> J. Med. Genet. 52: 186-194, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25539947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25539947</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25539947">Al-Hassnan et al. (2015)</a> noted that the ISCA2 gene is an essential component involved in the assembly of a mitochondrial iron-sulfur cluster (4Fe-4S) important for electron transfer and mitochondrial function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25539947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4, <a href="#2" class="mim-tip-reference" title="Alaimo, J. T., Besse, A., Alston, C. L., Pang, K., Appadurai, V., Samanta, M., Smpokou, P. McFarland, R., Taylor, R. W., Bonnen, P. E. <strong>Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion.</strong> Hum. Mutat. 39: 537-549, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29297947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29297947</a>] [<a href="https://doi.org/10.1002/humu.23396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29297947">Alaimo et al. (2018)</a> identified a homozygous G77S mutation in the ISCA2 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Dermal fibroblasts from 1 of the patients showed diminished mitochondrial membrane potential, variably decreased or increased mitochondrial enzyme complexes, decreased oxygen consumption, and decreased ATP production compared to controls, consistent with mitochondrial dysfunction. There was a decrease in complex II activity and mildly decreased complex IV activity, with intact complexes I and III. The mitochondria also showed morphologic defects as well as decreased mtDNA content, to about 25% of normal values. Patient cells also showed decreased levels of protein lipoylation, indicating a defect in the production of lipoic acid, presumably due to faulty Fe-S cluster generation and specifically affecting the 4Fe-4S-dependent enzyme LIAS (<a href="/entry/607031">607031</a>). Knockdown of ISCA2 using shRNA resulted in similar cellular abnormalities and defects involving 4Fe-4S-dependent proteins, but not 2Fe-2S proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29297947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 10 children from 9 unrelated consanguineous Saudi families with MMDS4, <a href="#3" class="mim-tip-reference" title="Alfadhel, M., Nashabat, M., Alrifai, M. T., Alshaalan, H., Al Mutairi, F., Al-Shahrani, S. A., Plecko, B., Almass, R., Alsagob, M., Almutairi, F. B., Al-Rumayyan, A., Al-Twaijri, W., Al-Owain, M., Taylor, R. W., Kaya, N. <strong>Further delineation of the phenotypic spectrum of ISCA2 defect: a report of ten new cases.</strong> Europ. J. Paediat. Neurol. 22: 46-55, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29122497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29122497</a>] [<a href="https://doi.org/10.1016/j.ejpn.2017.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29122497">Alfadhel et al. (2018)</a> identified the homozygous G77S founder mutation in the ISCA2 gene. Specific functional studies of the variant were not performed, but laboratory studies suggested a defect in the 4Fe-4S cluster. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29122497" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian infant with MMDS4, <a href="#6" class="mim-tip-reference" title="Toldo, I., Nosadini, M., Boscardin, C., Talenti, G., Manara, R., Lamantea, E., Legati, A., Ghezzi, D., Perilongo, G., Sartori, S. <strong>Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.</strong> Metab. Brain Dis. 33: 805-812, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29359243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29359243</a>] [<a href="https://doi.org/10.1007/s11011-017-0181-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29359243">Toldo et al. (2018)</a> identified compound heterozygous mutations in the ISCA2 gene (c.295delT, <a href="#0002">615317.0002</a> and S112G, <a href="#0003">615317.0003</a>). The mutations, which were found by next-generation sequencing of a panel of genes associated with mitochondrial disorders, segregated with the disorder in the family. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29359243" 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 6 patients from 5 consanguineous Arab families with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; <a href="/entry/616370">616370</a>), <a href="#1" class="mim-tip-reference" title="Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others. <strong>ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.</strong> J. Med. Genet. 52: 186-194, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25539947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25539947</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25539947">Al-Hassnan et al. (2015)</a> identified a homozygous c.229G-A transition in exon 3 of the ISCA2 gene (d.G74961032A), resulting in a gly77-to-ser (G77S) substitution at highly conserved residues in the Fe-S domain. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The mutation was not found in the dbSNP or 1000 Genomes Project databases or in 1,060 chromosomes from ethnically matched controls. Haplotype analysis indicated a founder effect estimated to have occurred 4,802 years ago. Functional studies of the ISCA2 variant were not performed, but <a href="#1" class="mim-tip-reference" title="Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others. <strong>ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.</strong> J. Med. Genet. 52: 186-194, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25539947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25539947</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25539947">Al-Hassnan et al. (2015)</a> noted that the ISCA2 gene is an essential component involved in the assembly of a mitochondrial iron-sulfur cluster (4Fe-4S) important for electron transfer and mitochondrial function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25539947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4, <a href="#2" class="mim-tip-reference" title="Alaimo, J. T., Besse, A., Alston, C. L., Pang, K., Appadurai, V., Samanta, M., Smpokou, P. McFarland, R., Taylor, R. W., Bonnen, P. E. <strong>Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion.</strong> Hum. Mutat. 39: 537-549, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29297947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29297947</a>] [<a href="https://doi.org/10.1002/humu.23396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29297947">Alaimo et al. (2018)</a> identified a homozygous G77S mutation in the ISCA2 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29297947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 10 children from 9 unrelated consanguineous Saudi families with MMDS4, <a href="#3" class="mim-tip-reference" title="Alfadhel, M., Nashabat, M., Alrifai, M. T., Alshaalan, H., Al Mutairi, F., Al-Shahrani, S. A., Plecko, B., Almass, R., Alsagob, M., Almutairi, F. B., Al-Rumayyan, A., Al-Twaijri, W., Al-Owain, M., Taylor, R. W., Kaya, N. <strong>Further delineation of the phenotypic spectrum of ISCA2 defect: a report of ten new cases.</strong> Europ. J. Paediat. Neurol. 22: 46-55, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29122497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29122497</a>] [<a href="https://doi.org/10.1016/j.ejpn.2017.10.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29122497">Alfadhel et al. (2018)</a> identified the homozygous G77S founder mutation in the ISCA2 gene. Specific functional studies of the variant were not performed, but laboratory studies suggested a defect in the 4Fe-4S cluster. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29122497" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs778755775 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs778755775;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/rs778755775?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=rs778755775" 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=rs778755775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Italian infant with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; <a href="/entry/616370">616370</a>), <a href="#6" class="mim-tip-reference" title="Toldo, I., Nosadini, M., Boscardin, C., Talenti, G., Manara, R., Lamantea, E., Legati, A., Ghezzi, D., Perilongo, G., Sartori, S. <strong>Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.</strong> Metab. Brain Dis. 33: 805-812, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29359243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29359243</a>] [<a href="https://doi.org/10.1007/s11011-017-0181-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29359243">Toldo et al. (2018)</a> identified compound heterozygous mutations in the ISCA2 gene: a 1-bp deletion (c.295delT), predicted to result in a frameshift and premature termination (Phe99LeufsTer18), and a c.334A-G transition, resulting in a ser112-to-gly (S112G; <a href="#0003">615317.0003</a>) substitution. The mutations, which were found by next-generation sequencing of a panel of genes associated with mitochondrial disorders, segregated with the disorder in the family. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29359243" 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>For discussion of the c.334A-G transition in the ISCA2 gene, resulting in a ser112-to-gly (S112G) substitution, that was found in compound heterozygous state in a patient with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; <a href="/entry/616370">616370</a>) by <a href="#6" class="mim-tip-reference" title="Toldo, I., Nosadini, M., Boscardin, C., Talenti, G., Manara, R., Lamantea, E., Legati, A., Ghezzi, D., Perilongo, G., Sartori, S. <strong>Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.</strong> Metab. Brain Dis. 33: 805-812, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29359243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29359243</a>] [<a href="https://doi.org/10.1007/s11011-017-0181-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29359243">Toldo et al. (2018)</a>, see <a href="#0002">615317.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29359243" 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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Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others.
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J. Med. Genet. 52: 186-194, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25539947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25539947</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25539947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmedgenet-2014-102592" target="_blank">Full Text</a>]
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<strong>Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion.</strong>
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Hum. Mutat. 39: 537-549, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29297947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29297947</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29297947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Alfadhel, M., Nashabat, M., Alrifai, M. T., Alshaalan, H., Al Mutairi, F., Al-Shahrani, S. A., Plecko, B., Almass, R., Alsagob, M., Almutairi, F. B., Al-Rumayyan, A., Al-Twaijri, W., Al-Owain, M., Taylor, R. W., Kaya, N.
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<strong>Further delineation of the phenotypic spectrum of ISCA2 defect: a report of ten new cases.</strong>
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Europ. J. Paediat. Neurol. 22: 46-55, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29122497/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29122497</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29122497" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R.
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<strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong>
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Molec. Biol. Cell 23: 1157-1166, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22323289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22323289</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22323289[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=22323289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Toldo, I., Nosadini, M., Boscardin, C., Talenti, G., Manara, R., Lamantea, E., Legati, A., Ghezzi, D., Perilongo, G., Sartori, S.
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<strong>Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.</strong>
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Metab. Brain Dis. 33: 805-812, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29359243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29359243</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29359243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s11011-017-0181-3" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 06/12/2018
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 5/18/2015<br>Matthew B. Gross - updated : 7/18/2013
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<a id="creationDate" class="mim-anchor"></a>
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Paul J. Converse : 7/18/2013
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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alopez : 08/28/2019
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<span class="mim-text-font">
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carol : 06/18/2018<br>carol : 06/15/2018<br>ckniffin : 06/12/2018<br>alopez : 05/19/2015<br>mcolton : 5/18/2015<br>ckniffin : 5/18/2015<br>mgross : 7/18/2013<br>mgross : 7/18/2013
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<span class="mim-font">
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<strong>*</strong> 615317
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IRON-SULFUR CLUSTER ASSEMBLY 2; ISCA2
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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IRON-SULFUR CLUSTER ASSEMBLY 2, S. CEREVISIAE, HOMOLOG OF
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: ISCA2</em></strong>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1208621008;
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<strong>
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<em>
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Cytogenetic location: 14q24.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:74,493,765-74,497,106 </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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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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14q24.3
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<span class="mim-font">
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Multiple mitochondrial dysfunctions syndrome 4
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<span class="mim-font">
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616370
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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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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<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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</h4>
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</div>
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<span class="mim-text-font">
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<p>ISCA2, like ISCA1 (611006) and IBA57 (615316), is part of the iron-sulfur cluster (ISC) assembly machinery in mitochondria. These 3 proteins function late in the biosynthetic pathway of mitochondrial 4Fe-4S proteins (Sheftel et al., 2012). </p>
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<br />
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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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</h4>
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<span class="mim-text-font">
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<p>Using cell fractionation, immunoblot analysis, and confocal microscopy, Sheftel et al. (2012) demonstrated mitochondrial localization of human ISCA2. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2013) mapped the ISCA2 gene to chromosome 14q24.3 based on an alignment of the ISCA2 sequence (GenBank BC032893) with the genomic sequence (GRCh37).</p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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<span class="mim-text-font">
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<p>Sheftel et al. (2012) used RNA interference to deplete HeLa cells of ISCA1, ISCA2, and IBA57 and observed swollen mitochondria devoid of cristae membranes. Depletion of these proteins also resulted in diminished activities of mitochondrial 4Fe-4S proteins, including aconitase (ACO2; 100850), respiratory complex I (see 602985), and lipoic acid synthase (LIAS; 607031). In contrast, cellular heme content and mitochondrial 2Fe-2S ferrochelatase (FECH; 612386) were unaffected. Sheftel et al. (2012) proposed that ISCA1, ISCA2, and IBA57 are specifically involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the ISC assembly pathway. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 6 patients from 5 consanguineous Arab families with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; 616370), Al-Hassnan et al. (2015) identified a homozygous missense mutation in the ISCA2 gene (G77S; 615317.0001). The mutation, which was found by a combination of autozygosity mapping and exome sequencing, segregated with the disorder in the families. Haplotype analysis indicated a founder effect. Patient cells showed decreased expression of ISCA2, ISCA1 (611006), and IBA57 (615316). Functional studies of the ISCA2 variant were not performed, but Al-Hassnan et al. (2015) noted that the ISCA2 gene is an essential component involved in the assembly of a mitochondrial iron-sulfur cluster (4Fe-4S) important for electron transfer and mitochondrial function. </p><p>In 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4, Alaimo et al. (2018) identified a homozygous G77S mutation in the ISCA2 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Dermal fibroblasts from 1 of the patients showed diminished mitochondrial membrane potential, variably decreased or increased mitochondrial enzyme complexes, decreased oxygen consumption, and decreased ATP production compared to controls, consistent with mitochondrial dysfunction. There was a decrease in complex II activity and mildly decreased complex IV activity, with intact complexes I and III. The mitochondria also showed morphologic defects as well as decreased mtDNA content, to about 25% of normal values. Patient cells also showed decreased levels of protein lipoylation, indicating a defect in the production of lipoic acid, presumably due to faulty Fe-S cluster generation and specifically affecting the 4Fe-4S-dependent enzyme LIAS (607031). Knockdown of ISCA2 using shRNA resulted in similar cellular abnormalities and defects involving 4Fe-4S-dependent proteins, but not 2Fe-2S proteins. </p><p>In 10 children from 9 unrelated consanguineous Saudi families with MMDS4, Alfadhel et al. (2018) identified the homozygous G77S founder mutation in the ISCA2 gene. Specific functional studies of the variant were not performed, but laboratory studies suggested a defect in the 4Fe-4S cluster. </p><p>In an Italian infant with MMDS4, Toldo et al. (2018) identified compound heterozygous mutations in the ISCA2 gene (c.295delT, 615317.0002 and S112G, 615317.0003). The mutations, which were found by next-generation sequencing of a panel of genes associated with mitochondrial disorders, segregated with the disorder in the family. Functional studies of the variant were not performed. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>3 Selected Examples):</strong>
|
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</span>
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</h4>
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ISCA2, GLY77SER
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<br />
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SNP: rs730882246,
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ClinVar: RCV000162184, RCV000170534, RCV000255374, RCV000310400
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 6 patients from 5 consanguineous Arab families with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; 616370), Al-Hassnan et al. (2015) identified a homozygous c.229G-A transition in exon 3 of the ISCA2 gene (d.G74961032A), resulting in a gly77-to-ser (G77S) substitution at highly conserved residues in the Fe-S domain. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The mutation was not found in the dbSNP or 1000 Genomes Project databases or in 1,060 chromosomes from ethnically matched controls. Haplotype analysis indicated a founder effect estimated to have occurred 4,802 years ago. Functional studies of the ISCA2 variant were not performed, but Al-Hassnan et al. (2015) noted that the ISCA2 gene is an essential component involved in the assembly of a mitochondrial iron-sulfur cluster (4Fe-4S) important for electron transfer and mitochondrial function. </p><p>In 2 unrelated patients, each born of consanguineous Saudi parents, with MMDS4, Alaimo et al. (2018) identified a homozygous G77S mutation in the ISCA2 gene. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. </p><p>In 10 children from 9 unrelated consanguineous Saudi families with MMDS4, Alfadhel et al. (2018) identified the homozygous G77S founder mutation in the ISCA2 gene. Specific functional studies of the variant were not performed, but laboratory studies suggested a defect in the 4Fe-4S cluster. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ISCA2, 1-BP DEL, 295T
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<br />
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SNP: rs778755775,
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gnomAD: rs778755775,
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ClinVar: RCV000656511, RCV001008511
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an Italian infant with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; 616370), Toldo et al. (2018) identified compound heterozygous mutations in the ISCA2 gene: a 1-bp deletion (c.295delT), predicted to result in a frameshift and premature termination (Phe99LeufsTer18), and a c.334A-G transition, resulting in a ser112-to-gly (S112G; 615317.0003) substitution. The mutations, which were found by next-generation sequencing of a panel of genes associated with mitochondrial disorders, segregated with the disorder in the family. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ISCA2, SER112GLY
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<br />
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SNP: rs767352340,
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gnomAD: rs767352340,
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ClinVar: RCV000627031, RCV002529803
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.334A-G transition in the ISCA2 gene, resulting in a ser112-to-gly (S112G) substitution, that was found in compound heterozygous state in a patient with multiple mitochondrial dysfunctions syndrome-4 (MMDS4; 616370) by Toldo et al. (2018), see 615317.0002. </p>
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</span>
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</div>
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<strong>REFERENCES</strong>
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Al-Hassnan, Z. N., Al-Dosary, M., Alfadhel, M., Faqeih, E. A., Alsagob, M., Kenana, R., Almass, R., Al-Harazi, O. S., Al-Hindi, H., Malibari, O. I., Almutari, F. B., Tulbah, S., and 9 others.
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<strong>ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.</strong>
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J. Med. Genet. 52: 186-194, 2015.
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[PubMed: 25539947]
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[Full Text: https://doi.org/10.1136/jmedgenet-2014-102592]
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Alaimo, J. T., Besse, A., Alston, C. L., Pang, K., Appadurai, V., Samanta, M., Smpokou, P. McFarland, R., Taylor, R. W., Bonnen, P. E.
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<strong>Loss-of-function mutations in ISCA2 disrupt 4Fe-4S cluster machinery and cause a fatal leukodystrophy with hyperglycinemia and mtDNA depletion.</strong>
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Hum. Mutat. 39: 537-549, 2018.
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[PubMed: 29297947]
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[Full Text: https://doi.org/10.1002/humu.23396]
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Alfadhel, M., Nashabat, M., Alrifai, M. T., Alshaalan, H., Al Mutairi, F., Al-Shahrani, S. A., Plecko, B., Almass, R., Alsagob, M., Almutairi, F. B., Al-Rumayyan, A., Al-Twaijri, W., Al-Owain, M., Taylor, R. W., Kaya, N.
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<strong>Further delineation of the phenotypic spectrum of ISCA2 defect: a report of ten new cases.</strong>
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Europ. J. Paediat. Neurol. 22: 46-55, 2018.
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[PubMed: 29122497]
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[Full Text: https://doi.org/10.1016/j.ejpn.2017.10.003]
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 7/18/2013.
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<p class="mim-text-font">
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Sheftel, A. D., Wilbrecht, C., Stehling, O., Niggemeyer, B., Elsasser, H.-P., Muhlenhoff, U., Lill, R.
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<strong>The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.</strong>
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Molec. Biol. Cell 23: 1157-1166, 2012.
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[PubMed: 22323289]
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[Full Text: https://doi.org/10.1091/mbc.E11-09-0772]
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<p class="mim-text-font">
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Toldo, I., Nosadini, M., Boscardin, C., Talenti, G., Manara, R., Lamantea, E., Legati, A., Ghezzi, D., Perilongo, G., Sartori, S.
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<strong>Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.</strong>
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Metab. Brain Dis. 33: 805-812, 2018.
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[PubMed: 29359243]
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[Full Text: https://doi.org/10.1007/s11011-017-0181-3]
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Cassandra L. Kniffin - updated : 06/12/2018<br>Cassandra L. Kniffin - updated : 5/18/2015<br>Matthew B. Gross - updated : 7/18/2013
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Paul J. Converse : 7/18/2013
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alopez : 08/28/2019<br>carol : 06/18/2018<br>carol : 06/15/2018<br>ckniffin : 06/12/2018<br>alopez : 05/19/2015<br>mcolton : 5/18/2015<br>ckniffin : 5/18/2015<br>mgross : 7/18/2013<br>mgross : 7/18/2013
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