2957 lines
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Entry
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- *603921 - SUCCINATE-CoA LIGASE, ADP-FORMING, SUBUNIT BETA; SUCLA2
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- OMIM
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<p>
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<span class="h4">*603921</span>
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<br />
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<strong>Table of Contents</strong>
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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="#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/603921">Table View</a>
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<a href="#references"><strong>References</strong></a>
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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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</ul>
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<div 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=ENSG00000136143;t=ENST00000646932" 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=8803" 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=603921" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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=ENSG00000136143;t=ENST00000646932" 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_003850" 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_003850" 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=603921" 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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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=06798&isoform_id=06798_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/SUCLA2" 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/3766197,7022728,7023369,7328935,11321583,20380655,30268174,33150622,34364605,94730427,119629180,119629181,119629182,119629183,189054910,194379366,194388002,221045470,221045930,311349138,311349140,311349142,311349144,311349146,311349148,311349150,311349152,311349154,311349156,311349158,311349160,311349162,311349164,311349166,311349168,311349170,311349172,311349174,311349176,311349178,311349180,311349182,311349184,311349186,311349188,311349190,311349192,311349194,311349196,311349198,311349200,311349202,311349204,311349206,311349208,311349210,311349212,311349214,311349216,957950527,957950530" 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/Q9P2R7" 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=8803" 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=ENSG00000136143;t=ENST00000646932" 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=SUCLA2" 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=SUCLA2" 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+8803" 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/SUCLA2" 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:8803" 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/8803" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr13&hgg_gene=ENST00000646932.1&hgg_start=47942656&hgg_end=48001273&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 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:11448" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/sucla2" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603921[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603921[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/ENSG00000136143" 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=SUCLA2" 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=SUCLA2" 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=SUCLA2" 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=SUCLA2&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/PA36245" 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:11448" 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/FBgn0037643.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:1306775" 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/SUCLA2#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:1306775" 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/8803/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=8803" 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=WBGene00009812;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-040426-1963" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:8803" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=SUCLA2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603921
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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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SUCCINATE-CoA LIGASE, ADP-FORMING, SUBUNIT BETA; SUCLA2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ATP-SPECIFIC SUCCINYL-CoA SYNTHETASE, BETA SUBUNIT<br />
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A-BETA
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SUCLA2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SUCLA2</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/13/158?start=-3&limit=10&highlight=158">13q14.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr13:47942656-48001273&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">13:47,942,656-48,001,273</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
|
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<a href="/geneMap/13/158?start=-3&limit=10&highlight=158">
|
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13q14.2
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</a>
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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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Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
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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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<a href="/entry/612073"> 612073 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="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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<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">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/603921" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/603921" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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<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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<p />
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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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<a id="text" class="mim-anchor"></a>
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<h4>
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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.">
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<p>The SUCLA2 gene encodes the beta-subunit of the ADP-forming succinyl-CoA synthetase (SCS-A; <a href="https://enzyme.expasy.org/EC/6.2.1.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 6.2.1.5</a>). SCS is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinyl-CoA from succinate and CoA. The reverse reaction occurs in the Krebs cycle, while the forward reaction may produce succinyl-CoA for activation of ketone bodies and heme synthesis. GTP-specific (SCS-G; <a href="https://enzyme.expasy.org/EC/6.2.1.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 6.2.1.4</a>) and ATP-specific (SCS-A) isoforms of SCS catalyze GTP-dependent and ATP-dependent reactions, respectively. SCS is composed of an invariant alpha subunit (SUCLG1; <a href="/entry/611224">611224</a>) and a beta subunit that determines the enzyme's nucleotide specificity (summary by <a href="#5" class="mim-tip-reference" title="Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., Lambeth, D. O. <strong>Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.</strong> J. Biol. Chem. 273: 27580-27586, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9765291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9765291</a>] [<a href="https://doi.org/10.1074/jbc.273.42.27580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9765291">Johnson et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9765291" 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 the partial protein sequences of pigeon A-beta and G-beta (<a href="/entry/603922">603922</a>), the beta subunits of A-SCS and G-SCS, respectively, <a href="#5" class="mim-tip-reference" title="Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., Lambeth, D. O. <strong>Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.</strong> J. Biol. Chem. 273: 27580-27586, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9765291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9765291</a>] [<a href="https://doi.org/10.1074/jbc.273.42.27580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9765291">Johnson et al. (1998)</a> isolated cDNAs from the corresponding pigeon genes. By searching EST databases with the pigeon gene sequences, they identified human and mouse A-beta and G-beta cDNAs. The predicted 411-amino acid human A-beta protein shares 89 to 95% identity with that of pigeon, mouse, and pig, and 38 to 48% identity with the beta subunit of bacterial SCSs. Human A-beta and G-beta are 53% identical. RT-PCR revealed that A-beta is widely expressed, and the levels of A-beta mRNA exceed those of G-beta in nearly all tissues. However, <a href="#5" class="mim-tip-reference" title="Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., Lambeth, D. O. <strong>Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.</strong> J. Biol. Chem. 273: 27580-27586, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9765291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9765291</a>] [<a href="https://doi.org/10.1074/jbc.273.42.27580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9765291">Johnson et al. (1998)</a> noted that enzyme assays using rat and mouse tissues suggested that the relative levels of expression are not directly related to the relative enzymatic activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9765291" 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="#3" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 5/29/2015."None>Gross (2015)</a> mapped the SUCLA2 gene to chromosome 13q14.2 based on an alignment of the SUCLA2 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF087890" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF087890</a>) with the genomic sequence (GRCh38).</p>
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<p>In a total of 16 patients from the Faroe Islands with encephalomyopathic mitochondrial DNA depletion syndrome-5 and mild methylmalonic aciduria (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#6" class="mim-tip-reference" title="Ostergaard, E., Hansen, F. J., Sorensen, N., Duno, M., Vissing, J., Larsen, P. L., Faeroe, O., Thorgrimsson, S., Wibrand, F., Christensen, E., Schwartz, M. <strong>Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations.</strong> Brain 130: 853-861, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17287286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17287286</a>] [<a href="https://doi.org/10.1093/brain/awl383" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17287286">Ostergaard et al. (2007)</a> and <a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> independently identified a homozygous founder mutation in the SUCLA2 gene (<a href="#0002">603921.0002</a>). <a href="#2" class="mim-tip-reference" title="Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S., Saada, A. <strong>Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.</strong> Am. J. Hum. Genet. 76: 1081-1086, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877282</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15877282[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15877282">Elpeleg et al. (2005)</a> identified a homozygous mutation in the SUCLA2 gene (<a href="#0001">603921.0001</a>) in 2 first cousins from a consanguineous Muslim family with encephalomyopathy and mitochondrial DNA depletion syndrome, but urinary organic acid profiles were not reported in the 2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17287286+15877282+17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> identified 2 additional SUCLA2 mutations (<a href="#0003">603921.0003</a>; <a href="#0004">603921.0004</a>) in Italian patients with a similar disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603921[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2137715433 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2137715433;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2137715433" 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=rs2137715433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 first cousins from a consanguineous Muslim family with encephalomyopathic mitochondrial DNA depletion syndrome-5 (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#2" class="mim-tip-reference" title="Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S., Saada, A. <strong>Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.</strong> Am. J. Hum. Genet. 76: 1081-1086, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877282</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15877282[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15877282">Elpeleg et al. (2005)</a> identified a homozygous deletion/insertion in the SUCLA2 gene. There was a complex genomic arrangement at the 3-prime end of exon 6, with a 43-bp deletion encompassing the last 14 bp of exon 6 and the first 29 bp of intron 6, and a 5-bp insertion. Two amplification products were generated: both skipped exon 6, and 1 also lacked the first 74 bp of exon 7. The mutation was not identified in 105 Muslim Arab controls. Skeletal muscle mitochondria from the patients showed significantly decreased activity of complexes I and IV; activities of complexes III and V were less affected. Skeletal muscle DNA from the patients showed a decreased ratio of mtDNA to nuclear DNA (32% of normal values). Urinary organic acids were not evaluated. <a href="#2" class="mim-tip-reference" title="Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S., Saada, A. <strong>Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.</strong> Am. J. Hum. Genet. 76: 1081-1086, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877282</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15877282[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/430843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15877282">Elpeleg et al. (2005)</a> postulated a defect in the last step of the mitochondrial deoxyribonucleoside triphosphate (dNTP) salvage pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15877282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs113994161 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994161;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/rs113994161?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=rs113994161" 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=rs113994161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000020560" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020560" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020560</a>
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<p>In a total of 16 patients from the Faroe Islands with encephalomyopathic mtDNA depletion syndrome and mild methylmalonic aciduria (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#6" class="mim-tip-reference" title="Ostergaard, E., Hansen, F. J., Sorensen, N., Duno, M., Vissing, J., Larsen, P. L., Faeroe, O., Thorgrimsson, S., Wibrand, F., Christensen, E., Schwartz, M. <strong>Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations.</strong> Brain 130: 853-861, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17287286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17287286</a>] [<a href="https://doi.org/10.1093/brain/awl383" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17287286">Ostergaard et al. (2007)</a> and <a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> independently identified a homozygous G-to-A transition in intron 4 of the SUCLA2 gene, resulting in the skipping of exon 4 and a truncated protein. <a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> referred to the mutation as 534+1G-A. Haplotype analysis indicated a founder effect. The carrier and disease frequencies in this population were estimated to be 2% and 1 in 2,500, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17287286+17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908537 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908537;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121908537" 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=rs121908537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated patients with encephalomyopathic mitochondrial DNA depletion with methylmalonic aciduria (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> identified a homozygous 850C-T transition in exon 7 of the SUCLA2 gene, resulting in a gly118-to-arg (G118R) substitution. Both patients originated from southern Italy. A distantly affected relative of 1 of the patients was found to be compound heterozygous for G118R and R284C (<a href="#0004">603921.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121908538 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908538;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/rs121908538?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=rs121908538" 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=rs121908538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006344 OR RCV002293407" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006344, RCV002293407" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006344...</a>
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<p>In a boy with encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#1" class="mim-tip-reference" title="Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A. <strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong> Brain 130: 862-874, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>] [<a href="https://doi.org/10.1093/brain/awl389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17301081">Carrozzo et al. (2007)</a> identified compound heterozygosity for 2 mutations in the SUCLA2 gene: a 352G-A transition in exon 3, resulting in an arg284-to-cys (R284C) substitution, and G118R (<a href="#0003">603921.0003</a>). The father was from southern Italy and the mother from Romania. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITHOUT METHYLMALONIC ACIDURIA)</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515462 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515462;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs397515462" 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=rs397515462" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056273" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056273" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056273</a>
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<p>In 2 Iranian cousins from a consanguineous kindred with encephalomyopathic mitochondrial DNA depletion syndrome-5 (MTDPS5; <a href="/entry/612073">612073</a>), <a href="#4" class="mim-tip-reference" title="Jaberi, E., Chitsazian, F., Ali Shahidi, G., Rohani, M., Sina, F., Safari, I., Malakouti Nejad, M., Houshmand, M., Klotzle, B., Elahi, E. <strong>The novel mutation p.Asp251Asn in the beta-subunit of succinate-CoA ligase causes encephalomyopathy and elevated succinylcarnitine.</strong> J. Hum. Genet. 58: 526-530, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23759946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23759946</a>] [<a href="https://doi.org/10.1038/jhg.2013.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23759946">Jaberi et al. (2013)</a> identified a homozygous c.751G-A transition in the SUCLA2 gene, resulting in an asp251-to-asn (D251N) substitution at a highly conserved residue in the ATP-grasp domain. The mutation was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder, and was not present in 200 ethnically matched control individuals. Molecular modeling suggested that the mutation may cause structural changes that affect protein function. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23759946" 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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Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A.
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<strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong>
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Brain 130: 862-874, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17301081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17301081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17301081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awl389" target="_blank">Full Text</a>]
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Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S., Saada, A.
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<strong>Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.</strong>
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Am. J. Hum. Genet. 76: 1081-1086, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877282</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15877282[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=15877282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Jaberi, E., Chitsazian, F., Ali Shahidi, G., Rohani, M., Sina, F., Safari, I., Malakouti Nejad, M., Houshmand, M., Klotzle, B., Elahi, E.
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<strong>The novel mutation p.Asp251Asn in the beta-subunit of succinate-CoA ligase causes encephalomyopathy and elevated succinylcarnitine.</strong>
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J. Hum. Genet. 58: 526-530, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23759946/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23759946</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23759946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/jhg.2013.45" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Johnson1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., Lambeth, D. O.
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<strong>Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.</strong>
|
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J. Biol. Chem. 273: 27580-27586, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9765291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9765291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9765291" 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/10.1074/jbc.273.42.27580" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Ostergaard2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ostergaard, E., Hansen, F. J., Sorensen, N., Duno, M., Vissing, J., Larsen, P. L., Faeroe, O., Thorgrimsson, S., Wibrand, F., Christensen, E., Schwartz, M.
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<strong>Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations.</strong>
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Brain 130: 853-861, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17287286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17287286</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17287286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awl383" target="_blank">Full Text</a>]
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</p>
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<a id="contributors" class="mim-anchor"></a>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 05/29/2015
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 9/23/2013<br>Cassandra L. Kniffin - updated : 5/22/2008<br>Cassandra L. Kniffin - updated : 8/29/2007<br>Victor A. McKusick - updated : 8/16/2007<br>Cassandra L. Kniffin - updated : 5/23/2005
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Rebekah S. Rasooly : 6/18/1999
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/16/2024
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 04/17/2024<br>mgross : 05/29/2015<br>carol : 10/3/2013<br>ckniffin : 9/23/2013<br>carol : 12/17/2010<br>ckniffin : 12/9/2010<br>wwang : 5/27/2008<br>ckniffin : 5/22/2008<br>wwang : 9/4/2007<br>ckniffin : 8/29/2007<br>terry : 8/16/2007<br>carol : 9/20/2005<br>ckniffin : 8/31/2005<br>tkritzer : 5/23/2005<br>ckniffin : 5/23/2005<br>jlewis : 6/22/1999
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</span>
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</div>
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<div class="container visible-print-block">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 603921
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<div>
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<h3>
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<span class="mim-font">
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SUCCINATE-CoA LIGASE, ADP-FORMING, SUBUNIT BETA; SUCLA2
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ATP-SPECIFIC SUCCINYL-CoA SYNTHETASE, BETA SUBUNIT<br />
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A-BETA
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SUCLA2</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 13q14.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 13:47,942,656-48,001,273 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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13q14.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
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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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612073
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The SUCLA2 gene encodes the beta-subunit of the ADP-forming succinyl-CoA synthetase (SCS-A; EC 6.2.1.5). SCS is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinyl-CoA from succinate and CoA. The reverse reaction occurs in the Krebs cycle, while the forward reaction may produce succinyl-CoA for activation of ketone bodies and heme synthesis. GTP-specific (SCS-G; EC 6.2.1.4) and ATP-specific (SCS-A) isoforms of SCS catalyze GTP-dependent and ATP-dependent reactions, respectively. SCS is composed of an invariant alpha subunit (SUCLG1; 611224) and a beta subunit that determines the enzyme's nucleotide specificity (summary by Johnson et al., 1998). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using the partial protein sequences of pigeon A-beta and G-beta (603922), the beta subunits of A-SCS and G-SCS, respectively, Johnson et al. (1998) isolated cDNAs from the corresponding pigeon genes. By searching EST databases with the pigeon gene sequences, they identified human and mouse A-beta and G-beta cDNAs. The predicted 411-amino acid human A-beta protein shares 89 to 95% identity with that of pigeon, mouse, and pig, and 38 to 48% identity with the beta subunit of bacterial SCSs. Human A-beta and G-beta are 53% identical. RT-PCR revealed that A-beta is widely expressed, and the levels of A-beta mRNA exceed those of G-beta in nearly all tissues. However, Johnson et al. (1998) noted that enzyme assays using rat and mouse tissues suggested that the relative levels of expression are not directly related to the relative enzymatic activities. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2015) mapped the SUCLA2 gene to chromosome 13q14.2 based on an alignment of the SUCLA2 sequence (GenBank AF087890) with the genomic sequence (GRCh38).</p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a total of 16 patients from the Faroe Islands with encephalomyopathic mitochondrial DNA depletion syndrome-5 and mild methylmalonic aciduria (MTDPS5; 612073), Ostergaard et al. (2007) and Carrozzo et al. (2007) independently identified a homozygous founder mutation in the SUCLA2 gene (603921.0002). Elpeleg et al. (2005) identified a homozygous mutation in the SUCLA2 gene (603921.0001) in 2 first cousins from a consanguineous Muslim family with encephalomyopathy and mitochondrial DNA depletion syndrome, but urinary organic acid profiles were not reported in the 2 patients. </p><p>Carrozzo et al. (2007) identified 2 additional SUCLA2 mutations (603921.0003; 603921.0004) in Italian patients with a similar disorder. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
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<strong>5 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 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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SUCLA2, 43-BP DEL AND 5-BP INS
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|
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<br />
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|
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SNP: rs2137715433,
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|
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ClinVar: RCV000006341
|
|
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 first cousins from a consanguineous Muslim family with encephalomyopathic mitochondrial DNA depletion syndrome-5 (MTDPS5; 612073), Elpeleg et al. (2005) identified a homozygous deletion/insertion in the SUCLA2 gene. There was a complex genomic arrangement at the 3-prime end of exon 6, with a 43-bp deletion encompassing the last 14 bp of exon 6 and the first 29 bp of intron 6, and a 5-bp insertion. Two amplification products were generated: both skipped exon 6, and 1 also lacked the first 74 bp of exon 7. The mutation was not identified in 105 Muslim Arab controls. Skeletal muscle mitochondria from the patients showed significantly decreased activity of complexes I and IV; activities of complexes III and V were less affected. Skeletal muscle DNA from the patients showed a decreased ratio of mtDNA to nuclear DNA (32% of normal values). Urinary organic acids were not evaluated. Elpeleg et al. (2005) postulated a defect in the last step of the mitochondrial deoxyribonucleoside triphosphate (dNTP) salvage pathway. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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SUCLA2, IVS4DS, G-A, +1
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<br />
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|
|
SNP: rs113994161,
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|
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|
|
|
gnomAD: rs113994161,
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|
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ClinVar: RCV000020560
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a total of 16 patients from the Faroe Islands with encephalomyopathic mtDNA depletion syndrome and mild methylmalonic aciduria (MTDPS5; 612073), Ostergaard et al. (2007) and Carrozzo et al. (2007) independently identified a homozygous G-to-A transition in intron 4 of the SUCLA2 gene, resulting in the skipping of exon 4 and a truncated protein. Carrozzo et al. (2007) referred to the mutation as 534+1G-A. Haplotype analysis indicated a founder effect. The carrier and disease frequencies in this population were estimated to be 2% and 1 in 2,500, respectively. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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SUCLA2, GLY118ARG
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<br />
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SNP: rs121908537,
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ClinVar: RCV000006343
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</span>
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</div>
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<span class="mim-text-font">
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<p>In 2 unrelated patients with encephalomyopathic mitochondrial DNA depletion with methylmalonic aciduria (MTDPS5; 612073), Carrozzo et al. (2007) identified a homozygous 850C-T transition in exon 7 of the SUCLA2 gene, resulting in a gly118-to-arg (G118R) substitution. Both patients originated from southern Italy. A distantly affected relative of 1 of the patients was found to be compound heterozygous for G118R and R284C (603921.0004). </p>
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</span>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITH METHYLMALONIC ACIDURIA)</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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SUCLA2, ARG284CYS
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<br />
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SNP: rs121908538,
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gnomAD: rs121908538,
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ClinVar: RCV000006344, RCV002293407
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</span>
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</div>
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<span class="mim-text-font">
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<p>In a boy with encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria (MTDPS5; 612073), Carrozzo et al. (2007) identified compound heterozygosity for 2 mutations in the SUCLA2 gene: a 352G-A transition in exon 3, resulting in an arg284-to-cys (R284C) substitution, and G118R (603921.0003). The father was from southern Italy and the mother from Romania. </p>
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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>.0005 MITOCHONDRIAL DNA DEPLETION SYNDROME 5 (ENCEPHALOMYOPATHIC TYPE WITHOUT METHYLMALONIC ACIDURIA)</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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SUCLA2, ASP251ASN
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<br />
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SNP: rs397515462,
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ClinVar: RCV000056273
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Iranian cousins from a consanguineous kindred with encephalomyopathic mitochondrial DNA depletion syndrome-5 (MTDPS5; 612073), Jaberi et al. (2013) identified a homozygous c.751G-A transition in the SUCLA2 gene, resulting in an asp251-to-asn (D251N) substitution at a highly conserved residue in the ATP-grasp domain. The mutation was found by homozygosity mapping followed by candidate gene sequencing, segregated with the disorder, and was not present in 200 ethnically matched control individuals. Molecular modeling suggested that the mutation may cause structural changes that affect protein function. Functional studies were not performed. </p>
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</span>
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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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Carrozzo, R., Dionisi-Vici, C., Steuerwald, U., Lucioli, S., Deodato, F., Di Giandomenico, S., Bertini, E., Franke, B., Kluijtmans, L. A. J., Meschini, M. C., Rizzo, C., Piemonte, F., Rodenburg, R., Santer, R., Santorelli, F. M., van Rooij, A., Vermunt-de Koning, D., Morava, E., Wevers, R. A.
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<strong>SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia, and deafness.</strong>
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Brain 130: 862-874, 2007.
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[PubMed: 17301081]
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[Full Text: https://doi.org/10.1093/brain/awl389]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S., Saada, A.
|
|
<strong>Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.</strong>
|
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Am. J. Hum. Genet. 76: 1081-1086, 2005.
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[PubMed: 15877282]
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[Full Text: https://doi.org/10.1086/430843]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 5/29/2015.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Jaberi, E., Chitsazian, F., Ali Shahidi, G., Rohani, M., Sina, F., Safari, I., Malakouti Nejad, M., Houshmand, M., Klotzle, B., Elahi, E.
|
|
<strong>The novel mutation p.Asp251Asn in the beta-subunit of succinate-CoA ligase causes encephalomyopathy and elevated succinylcarnitine.</strong>
|
|
J. Hum. Genet. 58: 526-530, 2013.
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[PubMed: 23759946]
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[Full Text: https://doi.org/10.1038/jhg.2013.45]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., Lambeth, D. O.
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<strong>Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes.</strong>
|
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J. Biol. Chem. 273: 27580-27586, 1998.
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[PubMed: 9765291]
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[Full Text: https://doi.org/10.1074/jbc.273.42.27580]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ostergaard, E., Hansen, F. J., Sorensen, N., Duno, M., Vissing, J., Larsen, P. L., Faeroe, O., Thorgrimsson, S., Wibrand, F., Christensen, E., Schwartz, M.
|
|
<strong>Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations.</strong>
|
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Brain 130: 853-861, 2007.
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[PubMed: 17287286]
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[Full Text: https://doi.org/10.1093/brain/awl383]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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Contributors:
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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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Matthew B. Gross - updated : 05/29/2015<br>Cassandra L. Kniffin - updated : 9/23/2013<br>Cassandra L. Kniffin - updated : 5/22/2008<br>Cassandra L. Kniffin - updated : 8/29/2007<br>Victor A. McKusick - updated : 8/16/2007<br>Cassandra L. Kniffin - updated : 5/23/2005
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Rebekah S. Rasooly : 6/18/1999
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carol : 05/16/2024<br>mgross : 04/17/2024<br>mgross : 05/29/2015<br>carol : 10/3/2013<br>ckniffin : 9/23/2013<br>carol : 12/17/2010<br>ckniffin : 12/9/2010<br>wwang : 5/27/2008<br>ckniffin : 5/22/2008<br>wwang : 9/4/2007<br>ckniffin : 8/29/2007<br>terry : 8/16/2007<br>carol : 9/20/2005<br>ckniffin : 8/31/2005<br>tkritzer : 5/23/2005<br>ckniffin : 5/23/2005<br>jlewis : 6/22/1999
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