3254 lines
219 KiB
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3254 lines
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Entry
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- *608877 - VACUOLAR PROTEIN SORTING 13 HOMOLOG D; VPS13D
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608877</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608877">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="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=ENSG00000048707;t=ENST00000620676" 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=55187" 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=608877" 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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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000048707;t=ENST00000620676" 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_015378,NM_018156" 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_015378" 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=608877" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=10593&isoform_id=10593_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/VPS13D" 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/7329718,30704430,34328012,34364948,34531104,42406433,42406435,54607139,54607141,56800387,56800388,56800389,56800390,62020645,119592143,119592144,119592145,194381448,221045184,613504586" 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/Q5THJ4" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=55187" 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=ENSG00000048707;t=ENST00000620676" 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=VPS13D" 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=VPS13D" 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+55187" 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/VPS13D" 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:55187" 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/55187" 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=chr1&hgg_gene=ENST00000620676.6&hgg_start=12230030&hgg_end=12512047&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:23595" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608877[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=608877[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/VPS13D/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000048707" 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=VPS13D" 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=VPS13D" 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=VPS13D" 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=VPS13D&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/PA134970144" 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:23595" 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/FBgn0052113.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:2448530" 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/VPS13D#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:2448530" 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/55187/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=55187" 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=WBGene00016120;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-050912-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=VPS13D&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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608877
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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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VACUOLAR PROTEIN SORTING 13 HOMOLOG D; VPS13D
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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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VACUOLAR PROTEIN SORTING 13, YEAST, HOMOLOG OF, D
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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=VPS13D" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">VPS13D</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/1/167?start=-3&limit=10&highlight=167">1p36.22-p36.21</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:12230030-12512047&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'})">1:12,230,030-12,512,047</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/1/167?start=-3&limit=10&highlight=167">
|
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1p36.22-p36.21
|
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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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Spinocerebellar ataxia, autosomal recessive 4
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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/607317"> 607317 </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/608877" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/608877" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<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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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>The VPS13D gene encodes a ubiquitously expressed protein that plays an important role in mitochondrial size, autophagy, and clearance (summary by <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al., 2018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By searching databases for sequences similar to VPS13A (<a href="/entry/605978">605978</a>), followed by RT-PCR of lymphoid cell line and brain RNA, <a href="#5" class="mim-tip-reference" title="Velayos-Baeza, A., Vettori, A., Copley, R. R., Dobson-Stone, C., Monaco, A. P. <strong>Analysis of the human VPS13 gene family.</strong> Genomics 84: 536-549, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498460</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.04.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498460">Velayos-Baeza et al. (2004)</a> cloned VPS13D. They identified 2 main splice variants, variant 1A and variant 2A, based on the presence or absence of exon 40, respectively, and they identified 4 different 3-prime end splice variants in the databases. Variant 1A encodes a deduced 4,388-amino acid protein, and variant 2A encodes a deduced 4,363-amino acid protein. VPS13D shares significant similarity with yeast Vps13 and other human VPS13 proteins, mostly in the N and C termini. Northern blot analysis detected VPS13D expression in all tissues tested. Variant 2A predominated in all tissues except brain and testis, in which variant 1A predominated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498460" 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="Anding, A. L., Wang, C., Chang, T.-K., Sliter, D. A., Powers, C. M., Hofmann, K., Youle, R. J., Baehrecke, E. H. <strong>Vps13D encodes a ubiquitin-binding protein that is required for the regulation of mitochondrial size and clearance.</strong> Curr. Biol. 28: 287-295, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29307555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29307555</a>] [<a href="https://doi.org/10.1016/j.cub.2017.11.064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29307555">Anding et al. (2018)</a> reported that human and Drosophila VPS13D share 33% amino acid identity. VPS13D contains a ubiquitin-binding UBA domain that is conserved from fly to human. Vps13d localized to lysosomes in Drosophila intestinal cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29307555" 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="#1" class="mim-tip-reference" title="Anding, A. L., Wang, C., Chang, T.-K., Sliter, D. A., Powers, C. M., Hofmann, K., Youle, R. J., Baehrecke, E. H. <strong>Vps13D encodes a ubiquitin-binding protein that is required for the regulation of mitochondrial size and clearance.</strong> Curr. Biol. 28: 287-295, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29307555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29307555</a>] [<a href="https://doi.org/10.1016/j.cub.2017.11.064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29307555">Anding et al. (2018)</a> found that Vps13D was an essential gene in Drosophila that was required for cell size reduction in midgut. Knockdown of Vps13d in larvae revealed that Vps13d acted specifically in developmental autophagy in midgut. Knockdown assays in Drosophila intestinal cells showed that Vps13d functioned downstream of Atg1 (see ULK1, <a href="/entry/603168">603168</a>) to mediate a change in ubiquitin associated with control of both mitochondrial morphology and autophagy. Further analysis showed that Vps13d knockdown resulted in a failure of mitochondrial clearance and enlarged mitochondria in Drosophila. Knockdown of human VPS13D in HeLa cells confirmed the phenotype observed in Drosophila. In vitro binding assays demonstrated that the Drosophila Vps13d UBA domain bound to lsy63 tetra-ubiquitin chains. Homozygous in-frame deletion of the Vps13d UBA domain in Drosophila drastically decreased survival rate, and midgut cells possessed enlarged mitochondria and larger cell size compared with controls, indicating that the UBA domain is required for mitochondrial clearance. Similarly, deletion of the human VPS13D UBA domain in HeLa cells resulted in significant mitochondrial morphology defects. The Vps13d mutant phenotype was similar to that of Drp1 (DNM1L; <a href="/entry/603850">603850</a>) mutant Drosophila, and investigation of VPS3D mutant HeLa cells suggested that VPS13D may influence DRP1 recruitment to mitochondria. Detailed analysis of Vps13d mutant Drosophila cells revealed that Vps13d was involved in mitochondrial fission and clearance of mitochondria by functioning downstream of Drp1 and upstream of induction of autophagy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29307555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Velayos-Baeza, A., Vettori, A., Copley, R. R., Dobson-Stone, C., Monaco, A. P. <strong>Analysis of the human VPS13 gene family.</strong> Genomics 84: 536-549, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498460</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.04.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498460">Velayos-Baeza et al. (2004)</a> determined that the VPS13D gene contains 70 exons and spans 280 kb. The translation start codon is in exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#5" class="mim-tip-reference" title="Velayos-Baeza, A., Vettori, A., Copley, R. R., Dobson-Stone, C., Monaco, A. P. <strong>Analysis of the human VPS13 gene family.</strong> Genomics 84: 536-549, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498460</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.04.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498460">Velayos-Baeza et al. (2004)</a> mapped the VPS13D gene to chromosome 1p36. They mapped the mouse Vps13d gene to chromosome 4E1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected members of 2 unrelated families (UM1 and LUB1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>), <a href="#3" class="mim-tip-reference" title="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a> identified compound heterozygous mutations in the VPS13D gene (<a href="#0001">608877.0001</a>-<a href="#0004">608877.0004</a>). The mutations in the first family were found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing; this family had previously been reported by <a href="#4" class="mim-tip-reference" title="Swartz, B. E., Burmeister, M., Somers, J. T., Rottach, K. G., Bespalova, I. N., Leigh, R. J. <strong>A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus.</strong> Ann. N.Y. Acad. Sci. 956: 441-444, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11960835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11960835</a>] [<a href="https://doi.org/10.1111/j.1749-6632.2002.tb02850.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11960835">Swartz et al. (2002)</a>. Mutations in the second family were also found by whole-exome sequencing. International collaboration studies sharing whole-exome data identified 5 additional patients with sporadic occurrence of the disorder who had biallelic mutations in the VPS13D gene. All mutations were confirmed by Sanger sequencing. All but 2 patients were compound heterozygous for a missense and nonsense or splice site mutation. Two patients with a more severe disorder had a combination of a nonsense or frameshift and a splice site mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11960835+29604224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 patients from 5 unrelated families of various ethnic descent with SCAR4, <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al. (2018)</a> identified homozygous or compound heterozygous mutations in the VPS13D gene (see, e.g., <a href="#0005">608877.0005</a>-<a href="#0007">608877.0007</a>). The families were collected using the GeneMatcher collaborative project. All mutations were found by exome sequencing and confirmed by Sanger sequencing to segregate with the disorder in the families. Affected members of 3 families were compound heterozygous for a loss-of-function and a missense mutation, whereas affected members of 2 families were homozygous or compound heterozygous for 2 missense mutations. Functional studies of the variants and studies of patient cells were not performed, but muscle biopsy of 1 patient showed mitochondrial abnormalities. <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al. (2018)</a> postulated a loss-of-function pathogenetic mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" 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="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a> noted that complete knockdown of the Vps13d homolog in Drosophila and mouse is embryonic lethal. Vps13d-null flies had abnormal mitochondrial morphology. Specific knockdown of the gene in motoneurons resulted in enlarged spherical mitochondria with loss of complexity of the mitochondrial network within neurons as well as impairment of the distribution of mitochondria in the peripheral axons of segmental nerves and neuromuscular junction synapses. The authors noted that these findings could represent defects in mitochondrial fission and fusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29604224" 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>.0001 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</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">rs1557680919 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557680919;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=rs1557680919" 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=rs1557680919" 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=RCV000680228 OR RCV001816689" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680228, RCV001816689" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680228...</a>
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<p>In affected members of a family (UM1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>), originally been reported by <a href="#4" class="mim-tip-reference" title="Swartz, B. E., Burmeister, M., Somers, J. T., Rottach, K. G., Bespalova, I. N., Leigh, R. J. <strong>A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus.</strong> Ann. N.Y. Acad. Sci. 956: 441-444, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11960835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11960835</a>] [<a href="https://doi.org/10.1111/j.1749-6632.2002.tb02850.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11960835">Swartz et al. (2002)</a>, <a href="#3" class="mim-tip-reference" title="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a> identified compound heterozygous mutations in the VPS13D gene: a c.3569G-A transition (c.3569G-A, NM_015378), resulting in a gly1190-to-asp (G1190D) substitution at a conserved residue and a c.3316C-T transition, resulting in a gln1106-to-ter (Q1106X; <a href="#0002">608877.0002</a>) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in the gnomAD database. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. Patient fibroblasts showed abnormal mitochondrial morphology, with high amounts of perinuclear spherical or donut-shaped objects and decreased mitochondrial branching compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11960835+29604224" 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 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</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">rs1557680710 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557680710;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=rs1557680710" 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=rs1557680710" 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=RCV000680229 OR RCV001816690" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680229, RCV001816690" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680229...</a>
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<p>For discussion of the c.3316C-T transition (c.3316C-T, NM_015378) in the VPS13D gene, resulting in a gln1106-to-ter (Q1106X) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>) by <a href="#3" class="mim-tip-reference" title="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a>, see <a href="#0001">608877.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29604224" 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 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
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VPS13D, ALA4210VAL (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs746736545;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs746736545</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs746736545 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs746736545;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/rs746736545?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=rs746736545" 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=rs746736545" 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=RCV000680230 OR RCV002532189" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680230, RCV002532189" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680230...</a>
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<p>In 2 German sisters (family LUB1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>), <a href="#3" class="mim-tip-reference" title="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a> identified compound heterozygous mutations in the VPS13D gene: a c.12629C-T transition (c.12629C-T, NM_015378), resulting in an ala4210-to-val (A4210V) substitution at a conserved residue, and a c.5409C-A transversion, resulting in a tyr1803-to-ter (Y1803X) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The A4210V variant was found at a low frequency (0.00004039) in the gnomAD database; the Y1803X variant was not found in the gnomAD database. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. Patient fibroblasts showed decreased mitochondrial branching and reduced ATP production compared to controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29604224" 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 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</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">rs1557684974 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557684974;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=rs1557684974" 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=rs1557684974" 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=RCV000680231" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680231" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680231</a>
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<p>For discussion of the c.5409C-A transversion (c.5409C-A, NM_015378) in the VPS13D gene, resulting in a tyr1803-to-ter (Y1803X) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>) by <a href="#3" class="mim-tip-reference" title="Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M. <strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong> Ann. Neurol. 83: 1075-1088, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>] [<a href="https://doi.org/10.1002/ana.25220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29604224">Seong et al. (2018)</a>, see <a href="#0003">608877.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29604224" 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 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</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">rs1557705968 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557705968;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=rs1557705968" 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=rs1557705968" 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=RCV000680232" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680232" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680232</a>
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<p>In 2 French Canadian brothers (family 1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>), <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al. (2018)</a> identified compound heterozygous mutations in the VPS13D gene: a 1-bp deletion (c.7332_7333del, NM_015378.3), predicted to result in a frameshift and premature termination (Val2445GlufsTer16), and a c.10562A-G transition, resulting in an asn3521-to-ser (N3521S; <a href="#0006">608877.0006</a>) substitution at a highly conserved residue in the SHR-binding domain. Functional studies of the variants were not performed, but muscle biopsy of 1 of the patients showed subsarcolemmal mitochondrial aggregates and mild lipidosis, suggesting mitochondrial dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1557737087 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557737087;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=rs1557737087" 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=rs1557737087" 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=RCV000680233" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680233" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680233</a>
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<p>For discussion of the c.10562A-G transition (c.10562A-G, NM_015378.3) in the VPS13D gene, resulting in an asn3521-to-ser (N3521S) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>) by <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al. (2018)</a>, see <a href="#0005">608877.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1557478316 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1557478316;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=rs1557478316" 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=rs1557478316" 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=RCV000680234 OR RCV002466560 OR RCV003163080" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680234, RCV002466560, RCV003163080" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680234...</a>
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<p>In a 9-year-old girl, born of consanguineous Egyptian parents (family 2), with autosomal recessive spinocerebellar ataxia-4 (SCAR4; <a href="/entry/607317">607317</a>), <a href="#2" class="mim-tip-reference" title="Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others. <strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong> Ann. Neurol. 83: 1089-1095, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>] [<a href="https://doi.org/10.1002/ana.25204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29518281">Gauthier et al. (2018)</a> identified a homozygous c.12683G-A transition (c.12683G-A, NM_015378.3) in the VPS13D gene, resulting in an arg4228-to-gln (R4228Q) substitution at a highly conserved residue in the C terminal. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" 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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Anding, A. L., Wang, C., Chang, T.-K., Sliter, D. A., Powers, C. M., Hofmann, K., Youle, R. J., Baehrecke, E. H.
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<strong>Vps13D encodes a ubiquitin-binding protein that is required for the regulation of mitochondrial size and clearance.</strong>
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Curr. Biol. 28: 287-295, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29307555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29307555</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29307555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.cub.2017.11.064" target="_blank">Full Text</a>]
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Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others.
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<strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong>
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Ann. Neurol. 83: 1089-1095, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29518281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29518281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.25204" target="_blank">Full Text</a>]
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Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M.
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<strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong>
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Ann. Neurol. 83: 1075-1088, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29604224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29604224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29604224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Swartz, B. E., Burmeister, M., Somers, J. T., Rottach, K. G., Bespalova, I. N., Leigh, R. J.
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<strong>A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus.</strong>
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Ann. N.Y. Acad. Sci. 956: 441-444, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11960835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11960835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11960835" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1749-6632.2002.tb02850.x" target="_blank">Full Text</a>]
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Velayos-Baeza, A., Vettori, A., Copley, R. R., Dobson-Stone, C., Monaco, A. P.
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<strong>Analysis of the human VPS13 gene family.</strong>
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Genomics 84: 536-549, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498460</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Cassandra L. Kniffin - updated : 09/11/2018
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Bao Lige - updated : 09/05/2018
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carol : 09/17/2018<br>carol : 09/14/2018<br>ckniffin : 09/11/2018<br>mgross : 09/05/2018<br>alopez : 03/28/2008<br>terry : 3/26/2008<br>mgross : 8/27/2004
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608877
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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VACUOLAR PROTEIN SORTING 13 HOMOLOG D; VPS13D
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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VACUOLAR PROTEIN SORTING 13, YEAST, HOMOLOG OF, D
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: VPS13D</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 1p36.22-p36.21
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:12,230,030-12,512,047 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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1p36.22-p36.21
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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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Spinocerebellar ataxia, autosomal recessive 4
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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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607317
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The VPS13D gene encodes a ubiquitously expressed protein that plays an important role in mitochondrial size, autophagy, and clearance (summary by Gauthier et al., 2018). </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>By searching databases for sequences similar to VPS13A (605978), followed by RT-PCR of lymphoid cell line and brain RNA, Velayos-Baeza et al. (2004) cloned VPS13D. They identified 2 main splice variants, variant 1A and variant 2A, based on the presence or absence of exon 40, respectively, and they identified 4 different 3-prime end splice variants in the databases. Variant 1A encodes a deduced 4,388-amino acid protein, and variant 2A encodes a deduced 4,363-amino acid protein. VPS13D shares significant similarity with yeast Vps13 and other human VPS13 proteins, mostly in the N and C termini. Northern blot analysis detected VPS13D expression in all tissues tested. Variant 2A predominated in all tissues except brain and testis, in which variant 1A predominated. </p><p>Anding et al. (2018) reported that human and Drosophila VPS13D share 33% amino acid identity. VPS13D contains a ubiquitin-binding UBA domain that is conserved from fly to human. Vps13d localized to lysosomes in Drosophila intestinal cells. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Anding et al. (2018) found that Vps13D was an essential gene in Drosophila that was required for cell size reduction in midgut. Knockdown of Vps13d in larvae revealed that Vps13d acted specifically in developmental autophagy in midgut. Knockdown assays in Drosophila intestinal cells showed that Vps13d functioned downstream of Atg1 (see ULK1, 603168) to mediate a change in ubiquitin associated with control of both mitochondrial morphology and autophagy. Further analysis showed that Vps13d knockdown resulted in a failure of mitochondrial clearance and enlarged mitochondria in Drosophila. Knockdown of human VPS13D in HeLa cells confirmed the phenotype observed in Drosophila. In vitro binding assays demonstrated that the Drosophila Vps13d UBA domain bound to lsy63 tetra-ubiquitin chains. Homozygous in-frame deletion of the Vps13d UBA domain in Drosophila drastically decreased survival rate, and midgut cells possessed enlarged mitochondria and larger cell size compared with controls, indicating that the UBA domain is required for mitochondrial clearance. Similarly, deletion of the human VPS13D UBA domain in HeLa cells resulted in significant mitochondrial morphology defects. The Vps13d mutant phenotype was similar to that of Drp1 (DNM1L; 603850) mutant Drosophila, and investigation of VPS3D mutant HeLa cells suggested that VPS13D may influence DRP1 recruitment to mitochondria. Detailed analysis of Vps13d mutant Drosophila cells revealed that Vps13d was involved in mitochondrial fission and clearance of mitochondria by functioning downstream of Drp1 and upstream of induction of autophagy. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Structure</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>Velayos-Baeza et al. (2004) determined that the VPS13D gene contains 70 exons and spans 280 kb. The translation start codon is in exon 2. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>By genomic sequence analysis, Velayos-Baeza et al. (2004) mapped the VPS13D gene to chromosome 1p36. They mapped the mouse Vps13d gene to chromosome 4E1. </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families (UM1 and LUB1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), Seong et al. (2018) identified compound heterozygous mutations in the VPS13D gene (608877.0001-608877.0004). The mutations in the first family were found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing; this family had previously been reported by Swartz et al. (2002). Mutations in the second family were also found by whole-exome sequencing. International collaboration studies sharing whole-exome data identified 5 additional patients with sporadic occurrence of the disorder who had biallelic mutations in the VPS13D gene. All mutations were confirmed by Sanger sequencing. All but 2 patients were compound heterozygous for a missense and nonsense or splice site mutation. Two patients with a more severe disorder had a combination of a nonsense or frameshift and a splice site mutation. </p><p>In 7 patients from 5 unrelated families of various ethnic descent with SCAR4, Gauthier et al. (2018) identified homozygous or compound heterozygous mutations in the VPS13D gene (see, e.g., 608877.0005-608877.0007). The families were collected using the GeneMatcher collaborative project. All mutations were found by exome sequencing and confirmed by Sanger sequencing to segregate with the disorder in the families. Affected members of 3 families were compound heterozygous for a loss-of-function and a missense mutation, whereas affected members of 2 families were homozygous or compound heterozygous for 2 missense mutations. Functional studies of the variants and studies of patient cells were not performed, but muscle biopsy of 1 patient showed mitochondrial abnormalities. Gauthier et al. (2018) postulated a loss-of-function pathogenetic mechanism. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Seong et al. (2018) noted that complete knockdown of the Vps13d homolog in Drosophila and mouse is embryonic lethal. Vps13d-null flies had abnormal mitochondrial morphology. Specific knockdown of the gene in motoneurons resulted in enlarged spherical mitochondria with loss of complexity of the mitochondrial network within neurons as well as impairment of the distribution of mitochondria in the peripheral axons of segmental nerves and neuromuscular junction synapses. The authors noted that these findings could represent defects in mitochondrial fission and fusion. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
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</div>
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|
|
|
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|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VPS13D, GLY1190ASP
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|
|
|
<br />
|
|
|
|
SNP: rs1557680919,
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|
|
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|
|
ClinVar: RCV000680228, RCV001816689
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family (UM1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), originally been reported by Swartz et al. (2002), Seong et al. (2018) identified compound heterozygous mutations in the VPS13D gene: a c.3569G-A transition (c.3569G-A, NM_015378), resulting in a gly1190-to-asp (G1190D) substitution at a conserved residue and a c.3316C-T transition, resulting in a gln1106-to-ter (Q1106X; 608877.0002) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Neither mutation was found in the gnomAD database. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. Patient fibroblasts showed abnormal mitochondrial morphology, with high amounts of perinuclear spherical or donut-shaped objects and decreased mitochondrial branching compared to controls. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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</div>
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|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VPS13D, GLN1106TER
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|
|
|
|
<br />
|
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|
|
SNP: rs1557680710,
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|
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ClinVar: RCV000680229, RCV001816690
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|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.3316C-T transition (c.3316C-T, NM_015378) in the VPS13D gene, resulting in a gln1106-to-ter (Q1106X) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317) by Seong et al. (2018), see 608877.0001. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
VPS13D, ALA4210VAL ({dbSNP rs746736545})
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|
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<br />
|
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|
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SNP: rs746736545,
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|
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gnomAD: rs746736545,
|
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|
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ClinVar: RCV000680230, RCV002532189
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 German sisters (family LUB1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), Seong et al. (2018) identified compound heterozygous mutations in the VPS13D gene: a c.12629C-T transition (c.12629C-T, NM_015378), resulting in an ala4210-to-val (A4210V) substitution at a conserved residue, and a c.5409C-A transversion, resulting in a tyr1803-to-ter (Y1803X) substitution. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The A4210V variant was found at a low frequency (0.00004039) in the gnomAD database; the Y1803X variant was not found in the gnomAD database. Analysis of patient cells indicated that the nonsense mutation resulted in nonsense-mediated mRNA decay. Patient fibroblasts showed decreased mitochondrial branching and reduced ATP production compared to controls. </p>
|
|
</span>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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VPS13D, TYR1803TER
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<br />
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SNP: rs1557684974,
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ClinVar: RCV000680231
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|
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</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.5409C-A transversion (c.5409C-A, NM_015378) in the VPS13D gene, resulting in a tyr1803-to-ter (Y1803X) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317) by Seong et al. (2018), see 608877.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</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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|
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VPS13D, 2-BP DEL, NT7332
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<br />
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SNP: rs1557705968,
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ClinVar: RCV000680232
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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 French Canadian brothers (family 1) with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), Gauthier et al. (2018) identified compound heterozygous mutations in the VPS13D gene: a 1-bp deletion (c.7332_7333del, NM_015378.3), predicted to result in a frameshift and premature termination (Val2445GlufsTer16), and a c.10562A-G transition, resulting in an asn3521-to-ser (N3521S; 608877.0006) substitution at a highly conserved residue in the SHR-binding domain. Functional studies of the variants were not performed, but muscle biopsy of 1 of the patients showed subsarcolemmal mitochondrial aggregates and mild lipidosis, suggesting mitochondrial dysfunction. </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>.0006 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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VPS13D, ASN3521SER
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<br />
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SNP: rs1557737087,
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ClinVar: RCV000680233
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</span>
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<span class="mim-text-font">
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<p>For discussion of the c.10562A-G transition (c.10562A-G, NM_015378.3) in the VPS13D gene, resulting in an asn3521-to-ser (N3521S) substitution, that was found in compound heterozygous state in affected members of a family with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317) by Gauthier et al. (2018), see 608877.0005. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>.0007 SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 4</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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VPS13D, ARG4228GLN
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<br />
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SNP: rs1557478316,
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ClinVar: RCV000680234, RCV002466560, RCV003163080
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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 9-year-old girl, born of consanguineous Egyptian parents (family 2), with autosomal recessive spinocerebellar ataxia-4 (SCAR4; 607317), Gauthier et al. (2018) identified a homozygous c.12683G-A transition (c.12683G-A, NM_015378.3) in the VPS13D gene, resulting in an arg4228-to-gln (R4228Q) substitution at a highly conserved residue in the C terminal. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. </p>
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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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<ol>
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<li>
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<p class="mim-text-font">
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Anding, A. L., Wang, C., Chang, T.-K., Sliter, D. A., Powers, C. M., Hofmann, K., Youle, R. J., Baehrecke, E. H.
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<strong>Vps13D encodes a ubiquitin-binding protein that is required for the regulation of mitochondrial size and clearance.</strong>
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Curr. Biol. 28: 287-295, 2018.
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[PubMed: 29307555]
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[Full Text: https://doi.org/10.1016/j.cub.2017.11.064]
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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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Gauthier, J., Meijer, I. A. Lessel, D., Mencacci, N. E., Krainc, D., Hempel, M., Tsiakas, K., Prokisch, H., Rossignol, E., Helm, M. H., Rodan, L. H., Karamchandani, J., and 11 others.
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<strong>Recessive mutations in VPS13D cause childhood onset movement disorders.</strong>
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Ann. Neurol. 83: 1089-1095, 2018.
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[PubMed: 29518281]
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[Full Text: https://doi.org/10.1002/ana.25204]
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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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Seong, E., Insolera, R., Dulovic, M., Kamsteeg, E.-J., Trinh, J., Bruggermann, N., Sandford, E., Li, S., Ozel, A. B., Li, J. Z., Jewett, T., Kievit, A. J. A., Munchau, A., Shakkottai, V., Klein, C., Collins, C. A., Lohmann, K., van de Warrenburg, B. P., Burmeister, M.
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<strong>Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.</strong>
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Ann. Neurol. 83: 1075-1088, 2018.
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[PubMed: 29604224]
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[Full Text: https://doi.org/10.1002/ana.25220]
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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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Swartz, B. E., Burmeister, M., Somers, J. T., Rottach, K. G., Bespalova, I. N., Leigh, R. J.
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<strong>A form of inherited cerebellar ataxia with saccadic intrusions, increased saccadic speed, sensory neuropathy, and myoclonus.</strong>
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Ann. N.Y. Acad. Sci. 956: 441-444, 2002.
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[PubMed: 11960835]
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[Full Text: https://doi.org/10.1111/j.1749-6632.2002.tb02850.x]
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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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Velayos-Baeza, A., Vettori, A., Copley, R. R., Dobson-Stone, C., Monaco, A. P.
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<strong>Analysis of the human VPS13 gene family.</strong>
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Genomics 84: 536-549, 2004.
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[PubMed: 15498460]
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[Full Text: https://doi.org/10.1016/j.ygeno.2004.04.012]
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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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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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Cassandra L. Kniffin - updated : 09/11/2018<br>Bao Lige - updated : 09/05/2018
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</div>
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Creation Date:
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<span class="mim-text-font">
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Patricia A. Hartz : 8/27/2004
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carol : 12/20/2019<br>carol : 09/17/2018<br>carol : 09/14/2018<br>ckniffin : 09/11/2018<br>mgross : 09/05/2018<br>alopez : 03/28/2008<br>terry : 3/26/2008<br>mgross : 8/27/2004
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