2947 lines
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Entry
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- *604436 - PYRIDOXAL PHOSPHATE-BINDING PROTEIN; PLPBP
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- OMIM
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<p>
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<span class="h4">*604436</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604436">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000147471;t=ENST00000328195" 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=11212" 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=604436" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000147471;t=ENST00000328195" 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_001349346,NM_001349347,NM_001349348,NM_001349349,NM_007198" 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_007198" 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=604436" 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=16060&isoform_id=16060_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/PLPBP" 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/4126978,6005842,12052758,12230426,15147391,49065490,119583764,119583765,119583766,119583767,119583768,158255706,193785623,1159261238,1159261254,1159261256,1159261258" 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/O94903" 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=11212" 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=ENSG00000147471;t=ENST00000328195" 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=PLPBP" 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=PLPBP" 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+11212" 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/PLPBP" 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:11212" 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/11212" 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=chr8&hgg_gene=ENST00000328195.8&hgg_start=37762546&hgg_end=37779768&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604436[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604436[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/PLPBP/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/ENSG00000147471" 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=PLPBP" 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=PLPBP" 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=PLPBP" 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=PLPBP&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/PA33810" 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:9457" 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/FBgn0039751.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:1891207" 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/PLPBP#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:1891207" 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/11212/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=11212" 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=WBGene00017286;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-030131-1378" 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=PLPBP&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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604436
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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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PYRIDOXAL PHOSPHATE-BINDING PROTEIN; PLPBP
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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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PROLINE SYNTHETASE COTRANSCRIBED, BACTERIA, HOMOLOG OF; PROSC
|
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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=PLPBP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PLPBP</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/8/197?start=-3&limit=10&highlight=197">8p11.23</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:37762546-37779768&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'})">8:37,762,546-37,779,768</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/8/197?start=-3&limit=10&highlight=197">
|
|
8p11.23
|
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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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Epilepsy, early-onset, 1, vitamin B6-dependent
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/617290"> 617290 </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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|
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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">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/604436" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604436" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
|
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<span class="mim-text-font">
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<p>The PROSC gene encodes a ubiquitously expressed cytoplasmic protein with a pyridoxal 5-prime phosphate (PLP)-binding barrel domain that likely plays a role in intracellular homeostatic regulation of PLP (summary by <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al., 2016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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 sequencing a 1.8-Mb segment of human 8p11.2, coupled with bioinformatics analyses, <a href="#2" class="mim-tip-reference" title="Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y. <strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong> J. Hum. Genet. 44: 337-342, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10496079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10496079</a>] [<a href="https://doi.org/10.1007/s100380050172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10496079">Ikegawa et al. (1999)</a> identified a novel gene. Since the P. aeruginosa homolog of this novel gene is located upstream of and may be cotranscribed with a known proline biosynthetic gene, the authors called the human gene PROSC, for 'proline synthetase cotranscribed, bacterial homolog.' Northern blot analysis detected a 2.6-kb PROSC transcript that was expressed in all human adult and fetal tissues tested. <a href="#2" class="mim-tip-reference" title="Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y. <strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong> J. Hum. Genet. 44: 337-342, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10496079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10496079</a>] [<a href="https://doi.org/10.1007/s100380050172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10496079">Ikegawa et al. (1999)</a> isolated cDNAs corresponding to the full-length PROSC transcript. The deduced 275-amino acid PROSC protein shares 86.5% sequence identity with mouse Prosc and 28% identity with its P. aeruginosa homolog. PROSC is predicted to be a soluble, cytoplasmic protein. It contains a putative N-linked glycosylation site and a putative cAMP- and cGMP-dependent protein kinase phosphorylation site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10496079" 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="#2" class="mim-tip-reference" title="Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y. <strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong> J. Hum. Genet. 44: 337-342, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10496079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10496079</a>] [<a href="https://doi.org/10.1007/s100380050172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10496079">Ikegawa et al. (1999)</a> determined that the PROSC gene spans 17.2 kb and contains 8 exons. It is oriented in a 5-prime to 3-prime direction from telomere to centromere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10496079" 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="#2" class="mim-tip-reference" title="Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y. <strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong> J. Hum. Genet. 44: 337-342, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10496079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10496079</a>] [<a href="https://doi.org/10.1007/s100380050172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10496079">Ikegawa et al. (1999)</a> mapped the PROSC gene between the proximal STS marker NIB1979 and the distal STS marker AFMA295ZD5 on chromosome 8p11.2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10496079" 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 7 patients from 5 unrelated families with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>), <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> identified homozygous or compound heterozygous mutations in the PROSC gene (see, e.g., <a href="#0001">604436.0001</a>-<a href="#0006">604436.0006</a>). The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing. Mutations in the 4 other patients were found by Sanger sequencing of the PROSC gene in 29 children with B6-responsive epilepsy. Patient plasma pyridoxal 5-prime phosphate levels in those receiving B6 treatment were increased compared to controls, and PLP levels in cultured patient fibroblasts were also increased. Complementation studies in PROSC-deficient E. coli showed that several of the mutations could not restore growth, indicating a loss-of-function effect. <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> noted that PLP is a highly reactive aldehyde and may interact nonspecifically with intracellular proteins and small molecules, resulting in a toxic effect. The genetic findings were consistent with a defect in intracellular homeostatic regulation of PLP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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">rs1057519273 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519273;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=rs1057519273" 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=rs1057519273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 affected members of a consanguineous Syrian family with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>), <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> identified a homozygous c.233C-G transversion (c.233C-G, NM_007198.3) in exon 3 of the PROSC gene, resulting in a ser78-to-ter (S78X) substitution. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, but was found in heterozygous state in 1 of 237 Swedish and 89 Syrian control individuals living in Sweden. Western blot analysis of patient cells showed no detectable PROSC, and complementation studies in PROSC-deficient E. coli showed that the S78X mutation could not restore growth, indicating a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 3.5-year-old girl (patient 4), born of consanguineous Indian parents, with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>), <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> identified a homozygous c.524T-C transition (c.524T-C, NM_007198.3) in exon 6 of the PROSC gene, resulting in a leu175-to-pro (L175P) substitution at a highly conserved residue. The variant was found at a low frequency (1 in 121,412 alleles) in the ExAC database. Western blot analysis of patient cells showed no detectable PROSC, and complementation studies in PROSC-deficient E. coli showed that the L175P mutation could not restore growth, indicating a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs767795673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs767795673;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/rs767795673?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=rs767795673" 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=rs767795673" 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=RCV000415527 OR RCV002521485" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415527, RCV002521485" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415527...</a>
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<p>In a 5.5-year-old German girl (patient 5) with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>), <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> identified compound heterozygous splice site mutations in the PROSC gene: a G-to-A transition in intron 2 (c.207+1G-A), and an A-to-G transition in intron 4 (c.320-2A-G; <a href="#0004">604436.0004</a>). The mutations, which were found by Sanger sequencing, segregated with the disorder in the family. The c.207+1G-A variant was found at a low frequency (4 in 121,408 alleles) in the ExAC database; the c.320-2A-G variant was not found in the ExAC database. Analysis of patient cells showed that the mutations resulted in abnormal splicing with several variant transcripts, including Val70IlefsTer6, Asp34_Tyr69del, and Ala107_Thr116del. Western blot analysis of patient cells showed no detectable PROSC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1057519424 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519424;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/rs1057519424?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=rs1057519424" 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=rs1057519424" 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=RCV000415559 OR RCV002524679" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415559, RCV002524679" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415559...</a>
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<p>For discussion of the A-to-G transition in intron 4 (c.320-2A-G) of the PROSC gene that was found in compound heterozygous state in a patient with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>) by <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a>, see <a href="#0003">604436.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs755946598 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs755946598;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/rs755946598?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=rs755946598" 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=rs755946598" 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=RCV000415592 OR RCV002521486" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415592, RCV002521486" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415592...</a>
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<p>In a 16-year-old Italian boy (patient 7) with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>), <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a> identified compound heterozygous missense mutations in the PROSC gene: a c.260C-T transition (c.260C-T, NM_007198.3) in exon 4, resulting in a pro87-to-leu (P87L) substitution at a residue conserved across higher organisms, and a c.722G-A transition in exon 8, resulting in an arg241-to-gln (R241Q; <a href="#0006">604436.0006</a>) substitution at a highly conserved residue. The mutations, which were found by Sanger sequencing, segregated with the disorder in the family. Both variants were found at low frequencies in the ExAC database (P87L in 2 of 121,410 alleles, and R241Q in 5 of 121,407 alleles). Complementation studies in PROSC-deficient E. coli showed that the R241Q mutation could not restore growth, indicating a loss-of-function effect, whereas the P87L mutation was able to restore growth, suggesting that the mutant protein retained some function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs760609867 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs760609867;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/rs760609867?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=rs760609867" 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=rs760609867" 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=RCV000415533 OR RCV003574769" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415533, RCV003574769" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415533...</a>
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<p>For discussion of the c.722G-A transition (c.722G-A, NM_007198.3) in exon 8 of the PROSC gene, resulting in an arg241-to-gln (R241Q) substitution, that was found in compound heterozygous state in a patient with early-onset vitamin B6-dependent epilepsy (EPEO1; <a href="/entry/617290">617290</a>) by <a href="#1" class="mim-tip-reference" title="Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T. <strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong> Am. J. Hum. Genet. 99: 1325-1337, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.10.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27912044">Darin et al. (2016)</a>, see <a href="#0005">604436.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<ol>
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<li>
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<a id="1" class="mim-anchor"></a>
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<a id="Darin2016" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T.
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<strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong>
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Am. J. Hum. Genet. 99: 1325-1337, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27912044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27912044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27912044[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27912044" 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.ajhg.2016.10.011" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Ikegawa1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y.
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<strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong>
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J. Hum. Genet. 44: 337-342, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10496079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10496079</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10496079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s100380050172" target="_blank">Full Text</a>]
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</p>
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</li>
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</ol>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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Contributors:
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</span>
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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 : 01/05/2017
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</span>
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</div>
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</div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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<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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Patti M. Sherman : 1/18/2000
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<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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alopez : 08/14/2023
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<div class="row collapse" id="mimCollapseEditHistory">
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<span class="mim-text-font">
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carol : 03/14/2019<br>carol : 01/07/2017<br>carol : 01/06/2017<br>ckniffin : 01/05/2017<br>carol : 03/21/2014<br>carol : 3/20/2014<br>mgross : 1/20/2000<br>psherman : 1/18/2000
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<span class="mim-font">
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<strong>*</strong> 604436
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<h3>
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PYRIDOXAL PHOSPHATE-BINDING PROTEIN; PLPBP
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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PROLINE SYNTHETASE COTRANSCRIBED, BACTERIA, HOMOLOG OF; PROSC
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</h4>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PLPBP</em></strong>
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<strong>
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<em>
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Cytogenetic location: 8p11.23
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Genomic coordinates <span class="small">(GRCh38)</span> : 8:37,762,546-37,779,768 </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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<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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Location
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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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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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8p11.23
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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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Epilepsy, early-onset, 1, vitamin B6-dependent
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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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617290
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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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</tbody>
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</table>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The PROSC gene encodes a ubiquitously expressed cytoplasmic protein with a pyridoxal 5-prime phosphate (PLP)-binding barrel domain that likely plays a role in intracellular homeostatic regulation of PLP (summary by Darin et al., 2016). </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 sequencing a 1.8-Mb segment of human 8p11.2, coupled with bioinformatics analyses, Ikegawa et al. (1999) identified a novel gene. Since the P. aeruginosa homolog of this novel gene is located upstream of and may be cotranscribed with a known proline biosynthetic gene, the authors called the human gene PROSC, for 'proline synthetase cotranscribed, bacterial homolog.' Northern blot analysis detected a 2.6-kb PROSC transcript that was expressed in all human adult and fetal tissues tested. Ikegawa et al. (1999) isolated cDNAs corresponding to the full-length PROSC transcript. The deduced 275-amino acid PROSC protein shares 86.5% sequence identity with mouse Prosc and 28% identity with its P. aeruginosa homolog. PROSC is predicted to be a soluble, cytoplasmic protein. It contains a putative N-linked glycosylation site and a putative cAMP- and cGMP-dependent protein kinase phosphorylation site. </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>Ikegawa et al. (1999) determined that the PROSC gene spans 17.2 kb and contains 8 exons. It is oriented in a 5-prime to 3-prime direction from telomere to centromere. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ikegawa et al. (1999) mapped the PROSC gene between the proximal STS marker NIB1979 and the distal STS marker AFMA295ZD5 on chromosome 8p11.2. </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">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 7 patients from 5 unrelated families with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290), Darin et al. (2016) identified homozygous or compound heterozygous mutations in the PROSC gene (see, e.g., 604436.0001-604436.0006). The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing. Mutations in the 4 other patients were found by Sanger sequencing of the PROSC gene in 29 children with B6-responsive epilepsy. Patient plasma pyridoxal 5-prime phosphate levels in those receiving B6 treatment were increased compared to controls, and PLP levels in cultured patient fibroblasts were also increased. Complementation studies in PROSC-deficient E. coli showed that several of the mutations could not restore growth, indicating a loss-of-function effect. Darin et al. (2016) noted that PLP is a highly reactive aldehyde and may interact nonspecifically with intracellular proteins and small molecules, resulting in a toxic effect. The genetic findings were consistent with a defect in intracellular homeostatic regulation of PLP. </p>
|
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
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<strong>6 Selected Examples):</strong>
|
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</span>
|
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</h4>
|
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</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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PLPBP, SER78TER
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<br />
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SNP: rs1057519273,
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ClinVar: RCV000415554, RCV000627267
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In 3 affected members of a consanguineous Syrian family with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290), Darin et al. (2016) identified a homozygous c.233C-G transversion (c.233C-G, NM_007198.3) in exon 3 of the PROSC gene, resulting in a ser78-to-ter (S78X) substitution. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, but was found in heterozygous state in 1 of 237 Swedish and 89 Syrian control individuals living in Sweden. Western blot analysis of patient cells showed no detectable PROSC, and complementation studies in PROSC-deficient E. coli showed that the S78X mutation could not restore growth, indicating a loss-of-function effect. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
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|
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PLPBP, LEU175PRO
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<br />
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|
SNP: rs752753379,
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|
|
gnomAD: rs752753379,
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|
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ClinVar: RCV000415599
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 3.5-year-old girl (patient 4), born of consanguineous Indian parents, with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290), Darin et al. (2016) identified a homozygous c.524T-C transition (c.524T-C, NM_007198.3) in exon 6 of the PROSC gene, resulting in a leu175-to-pro (L175P) substitution at a highly conserved residue. The variant was found at a low frequency (1 in 121,412 alleles) in the ExAC database. Western blot analysis of patient cells showed no detectable PROSC, and complementation studies in PROSC-deficient E. coli showed that the L175P mutation could not restore growth, indicating a loss-of-function effect. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</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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PLPBP, IVS2DS, G-A, +1
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<br />
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SNP: rs767795673,
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gnomAD: rs767795673,
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ClinVar: RCV000415527, RCV002521485
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|
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</span>
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<span class="mim-text-font">
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<p>In a 5.5-year-old German girl (patient 5) with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290), Darin et al. (2016) identified compound heterozygous splice site mutations in the PROSC gene: a G-to-A transition in intron 2 (c.207+1G-A), and an A-to-G transition in intron 4 (c.320-2A-G; 604436.0004). The mutations, which were found by Sanger sequencing, segregated with the disorder in the family. The c.207+1G-A variant was found at a low frequency (4 in 121,408 alleles) in the ExAC database; the c.320-2A-G variant was not found in the ExAC database. Analysis of patient cells showed that the mutations resulted in abnormal splicing with several variant transcripts, including Val70IlefsTer6, Asp34_Tyr69del, and Ala107_Thr116del. Western blot analysis of patient cells showed no detectable PROSC. </p>
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</span>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</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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PLPBP, IVS4AS, A-G, -2
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<br />
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SNP: rs1057519424,
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gnomAD: rs1057519424,
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ClinVar: RCV000415559, RCV002524679
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</span>
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</div>
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<span class="mim-text-font">
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<p>For discussion of the A-to-G transition in intron 4 (c.320-2A-G) of the PROSC gene that was found in compound heterozygous state in a patient with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290) by Darin et al. (2016), see 604436.0003. </p>
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</span>
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</div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</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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PLPBP, PRO87LEU
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<br />
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SNP: rs755946598,
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gnomAD: rs755946598,
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ClinVar: RCV000415592, RCV002521486
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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 16-year-old Italian boy (patient 7) with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290), Darin et al. (2016) identified compound heterozygous missense mutations in the PROSC gene: a c.260C-T transition (c.260C-T, NM_007198.3) in exon 4, resulting in a pro87-to-leu (P87L) substitution at a residue conserved across higher organisms, and a c.722G-A transition in exon 8, resulting in an arg241-to-gln (R241Q; 604436.0006) substitution at a highly conserved residue. The mutations, which were found by Sanger sequencing, segregated with the disorder in the family. Both variants were found at low frequencies in the ExAC database (P87L in 2 of 121,410 alleles, and R241Q in 5 of 121,407 alleles). Complementation studies in PROSC-deficient E. coli showed that the R241Q mutation could not restore growth, indicating a loss-of-function effect, whereas the P87L mutation was able to restore growth, suggesting that the mutant protein retained some function. </p>
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</span>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 EPILEPSY, EARLY-ONSET, 1, VITAMIN B6-DEPENDENT</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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PLPBP, ARG241GLN
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<br />
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SNP: rs760609867,
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gnomAD: rs760609867,
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ClinVar: RCV000415533, RCV003574769
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</span>
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</div>
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<span class="mim-text-font">
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<p>For discussion of the c.722G-A transition (c.722G-A, NM_007198.3) in exon 8 of the PROSC gene, resulting in an arg241-to-gln (R241Q) substitution, that was found in compound heterozygous state in a patient with early-onset vitamin B6-dependent epilepsy (EPEO1; 617290) by Darin et al. (2016), see 604436.0005. </p>
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</span>
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</div>
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</div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Darin, N., Reid, E., Prunetti, L., Samuelsson, L., Husain, R. A., Wilson, M., El Yacoubi, B., Footitt, E., Chong, W. K., Wilson, L. C., Prunty, H., Pope, S., Heales, S., Lascelles, L., Champion, M., Wassmer, E., Veggiotti, P., de Crecy-Lagard, V., Mills, P. B., Clayton, P. T.
|
|
<strong>Mutations in PROSC disrupt cellular pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy.</strong>
|
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Am. J. Hum. Genet. 99: 1325-1337, 2016.
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[PubMed: 27912044]
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.10.011]
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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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Ikegawa, S., Isomura, M., Koshizuka, Y., Nakamura, Y.
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<strong>Cloning and characterization of human and mouse PROSC (proline synthetase co-transcribed) genes.</strong>
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J. Hum. Genet. 44: 337-342, 1999.
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[PubMed: 10496079]
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[Full Text: https://doi.org/10.1007/s100380050172]
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</p>
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</li>
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</ol>
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<br />
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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 : 01/05/2017
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</span>
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</div>
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</div>
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</div>
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patti M. Sherman : 1/18/2000
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</span>
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</div>
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Edit History:
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<span class="mim-text-font">
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alopez : 08/14/2023<br>carol : 03/14/2019<br>carol : 01/07/2017<br>carol : 01/06/2017<br>ckniffin : 01/05/2017<br>carol : 03/21/2014<br>carol : 3/20/2014<br>mgross : 1/20/2000<br>psherman : 1/18/2000
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