4413 lines
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Entry
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- *606879 - PHOSPHOGLYCERATE DEHYDROGENASE; PHGDH
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- OMIM
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<p>
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<span class="h4">*606879</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="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606879">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 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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<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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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000092621;t=ENST00000641023" 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=26227" 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=606879" 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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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000092621;t=ENST00000641023" 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_006623,XM_011541226,XM_011541227,XM_011541228,XM_047417680,XM_047417682,XM_047417683,XR_007058634" 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_006623" 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=606879" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</div>
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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=06047&isoform_id=06047_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/PHGDH" 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/5771519,5771521,5771523,12653075,12655003,14335174,14335176,14335178,14335180,14335182,15030035,21264510,23308577,40226201,48145707,119577111,119577112,189067496,193787479,209402832,767903710,767903712,767903714,2217266433,2217266435,2217266437,2462507818,2462507820,2462507822,2462507824,2462507826,2462507828" 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/O43175" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=26227" 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=ENSG00000092621;t=ENST00000641023" 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=PHGDH" 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=PHGDH" 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+26227" 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/PHGDH" 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:26227" 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/26227" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr1&hgg_gene=ENST00000641023.2&hgg_start=119711934&hgg_end=119744215&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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:8923" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/phgdh" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606879[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=606879[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/PHGDH/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/ENSG00000092621" 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=PHGDH" 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=PHGDH" 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=PHGDH" 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=PHGDH&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/PA33264" 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:8923" 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/FBgn0032350.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:1355330" 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/PHGDH#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:1355330" 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/26227/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=26227" 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=WBGene00007836;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-030131-647" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:26227" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=PHGDH&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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606879
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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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PHOSPHOGLYCERATE DEHYDROGENASE; PHGDH
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
3-PHOSPHOGLYCERATE DEHYDROGENASE; 3PGDH
|
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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=PHGDH" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PHGDH</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>
|
|
Cytogenetic location: <a href="/geneMap/1/976?start=-3&limit=10&highlight=976">1p12</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:119711934-119744215&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">1:119,711,934-119,744,215</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<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>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=256520,601815" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
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</span>
|
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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>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/976?start=-3&limit=10&highlight=976">
|
|
1p12
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Neu-Laxova syndrome 1
|
|
|
|
</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/256520"> 256520 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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">
|
|
|
|
<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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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Phosphoglycerate dehydrogenase deficiency
|
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|
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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/601815"> 601815 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
|
</span>
|
|
</td>
|
|
</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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<p>3-Phosphoglycerate dehydrogenase (PHGDH; <a href="https://enzyme.expasy.org/EC/1.1.1.95" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.1.1.95</a>) catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first and rate-limiting step in the phosphorylated pathway of serine biosynthesis, using NAD+/NADH as a cofactor (summary by <a href="#6" class="mim-tip-reference" title="Cho, H. M., Jun, D. Y., Bae, M. A., Ahn, J. D., Kim, Y. H. <strong>Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene.</strong> Gene 245: 193-201, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10713460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10713460</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00009-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10713460">Cho et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10713460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Cho, H. M., Jun, D. Y., Bae, M. A., Ahn, J. D., Kim, Y. H. <strong>Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene.</strong> Gene 245: 193-201, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10713460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10713460</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00009-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10713460">Cho et al. (2000)</a> cloned a cDNA encoding phosphoglycerate dehydrogenase from a human Jurkat T-cell cDNA library. The deduced 533-amino acid protein, with a molecular mass of 56.8 kD, shares 94% sequence identity with rat liver 3-PGDH. Northern blot analysis detected a major 2.1-kb transcript at high levels in prostate, testis, ovary, brain, liver, kidney, and pancreas and at low levels in thymus, colon, and heart. A 710-bp transcript appeared as a weaker band in most tissues in which the 2.1-kb mRNA was expressed, was more significant than the 2.1-kb mRNA in heart, and was the only transcript present in skeletal muscle. The 2.1-kb transcript was also detected in most continuously growing tumor cells tested. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10713460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Cho, H. M., Jun, D. Y., Bae, M. A., Ahn, J. D., Kim, Y. H. <strong>Nucleotide sequence and differential expression of the human 3-phosphoglycerate dehydrogenase gene.</strong> Gene 245: 193-201, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10713460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10713460</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00009-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10713460">Cho et al. (2000)</a> found that TPA-induced monocytic differentiation of U937 cells, which also resulted in growth arrest, abruptly downregulated the expression of PHGDH. Removal of TPA restored cell growth through the retrodifferentiation process and subsequent expression of PHGDH. These findings suggested that the expression of PHGDH may be regulated at the transcriptional level depending on tissue specificity and cellular proliferative status. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10713460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., Chen, W. W., Barrett, F. G., and 15 others. <strong>Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.</strong> Nature 476: 346-350, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21760589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21760589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21760589[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21760589">Possemato et al. (2011)</a> developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, they screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, PHGDH is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of estrogen receptor-negative breast cancers. PHGDH catalyzes the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, caused a strong decrease in cell proliferation and a reduction in serine synthesis. <a href="#13" class="mim-tip-reference" title="Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., Chen, W. W., Barrett, F. G., and 15 others. <strong>Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.</strong> Nature 476: 346-350, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21760589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21760589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21760589[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21760589">Possemato et al. (2011)</a> found that PHGDH suppression does not affect intracellular serine levels, but causes a drop in levels of alpha-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. <a href="#13" class="mim-tip-reference" title="Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., Chen, W. W., Barrett, F. G., and 15 others. <strong>Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.</strong> Nature 476: 346-350, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21760589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21760589</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21760589[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10350" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21760589">Possemato et al. (2011)</a> concluded that certain breast cancers are dependent on increased serine pathway flux caused by PHGDH overexpression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21760589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., Sasaki, A. T., Anastasiou, D., and 14 others. <strong>Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis.</strong> Nature Genet. 43: 869-874, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21804546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21804546</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21804546[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.890" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21804546">Locasale et al. (2011)</a> found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through PHGDH. An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal number copy gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. <a href="#11" class="mim-tip-reference" title="Locasale, J. W., Grassian, A. R., Melman, T., Lyssiotis, C. A., Mattaini, K. R., Bass, A. J., Heffron, G., Metallo, C. M., Muranen, T., Sharfi, H., Sasaki, A. T., Anastasiou, D., and 14 others. <strong>Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis.</strong> Nature Genet. 43: 869-874, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21804546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21804546</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21804546[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.890" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21804546">Locasale et al. (2011)</a> concluded that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21804546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using 2 radiation hybrid panels, <a href="#10" class="mim-tip-reference" title="Klomp, L. W. J., de Koning, T. J., Malingre, H. E. M., van Beurden, E. A. C. M., Brink, M., Opdam, F. L., Duran, M., Jaeken, J., Pineda, M., van Maldergem, L., Poll-The, B. T., van den Berg, I. E. T., Berger, R. <strong>Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.</strong> Am. J. Hum. Genet. 67: 1389-1399, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055895[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055895">Klomp et al. (2000)</a> mapped the PHGDH gene to chromosome 1q12. However, by fluorescence in situ hybridization, <a href="#2" class="mim-tip-reference" title="Baek, J. Y., Jun, D. Y., Taub, D., Kim, Y. H. <strong>Assignment of human 3-phosphoglycerate dehydrogenase (PHGDH) to human chromosome band 1p12 by fluorescence in situ hybridization.</strong> Cytogenet. Cell Genet. 89: 6-7, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894924</a>] [<a href="https://doi.org/10.1159/000015577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10894924">Baek et al. (2000)</a> mapped the PHGDH gene to 1p12. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11055895+10894924" 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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To investigate the molecular basis of phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), <a href="#10" class="mim-tip-reference" title="Klomp, L. W. J., de Koning, T. J., Malingre, H. E. M., van Beurden, E. A. C. M., Brink, M., Opdam, F. L., Duran, M., Jaeken, J., Pineda, M., van Maldergem, L., Poll-The, B. T., van den Berg, I. E. T., Berger, R. <strong>Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.</strong> Am. J. Hum. Genet. 67: 1389-1399, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055895[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055895">Klomp et al. (2000)</a> characterized the PHGDH mRNA sequence and analyzed it for variations in 6 patients from 4 families with this disorder. Five patients in 3 different families were homozygous for a val490-to-met (V490M; <a href="#0001">606879.0001</a>) mutation and the sixth patient was homozygous for a val425-to-met (V425M; <a href="#0002">606879.0002</a>) mutation. Both mutations were located in the C terminus of the PHGDH gene. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurologic impairment in these patients, the data suggested an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., Klomp, L. W. J. <strong>Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.</strong> Hum. Mutat. 30: 749-756, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19235232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19235232</a>] [<a href="https://doi.org/10.1002/humu.20934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19235232">Tabatabaie et al. (2009)</a> identified 1 frameshift and 4 missense mutations in the PHGDH gene in 5 patients with phosphoglycerate dehydrogenase deficiency (see, e.g., <a href="#0003">606879.0003</a>-<a href="#0006">606879.0006</a>). Studies in patient fibroblasts showed significant, but incomplete, reduction with missense mutations, including the previously identified V490M and V425M substitutions. Transient overexpression studies in HEK293 cells and molecular modeling onto the partial crystal structure of 3-PGDH suggested that missense mutations associated with 3-PGDH deficiency either primarily affect substrate binding or result in very low residual enzymatic activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19235232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 2-month-old male infant, born to parents who came from the same area in the United Arab Emirates, with PHGDH deficiency, <a href="#7" class="mim-tip-reference" title="El-Hattab, A. W., Shaheen, R., Hertecant, J., Galadari, H. I., Albaqawi, B. S., Nabil, A., Alkuraya, F. S. <strong>On the phenotypic spectrum of serine biosynthesis.</strong> J. Inherit. Metab. Dis. 39: 373-381, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26960553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26960553</a>] [<a href="https://doi.org/10.1007/s10545-016-9921-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26960553">El-Hattab et al. (2016)</a> identified a homozygous missense mutation in the PHGDH gene (G429V; <a href="#0011">606879.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26960553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 individuals with PHGDHD from 2 unrelated families, <a href="#3" class="mim-tip-reference" title="Benke, P. J., Hidalgo, R. J., Braffman, B. H., Jans, J., van Gassen, K. L. I., Sunbul, R., El-Hattab, A. W. <strong>Infantile serine biosynthesis defect due to phosphoglycerate dehydrogenase deficiency: variability in phenotype and treatment response, novel mutations, and diagnostic challenges.</strong> J. Child Neurol. 32: 543-549, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135894</a>] [<a href="https://doi.org/10.1177/0883073817690094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135894">Benke et al. (2017)</a> identified homozygous or compound heterozygous mutations in the PHGDH gene (<a href="#0005">606879.0005</a> and <a href="#0012">606879.0012</a>). Studies in patient fibroblasts showed decreased PHGDH enzyme activity compared to control. Serine and glycine were low in patient plasma and CSF. By metabolomic analysis in plasma from these sisters and the boy previously reported by <a href="#7" class="mim-tip-reference" title="El-Hattab, A. W., Shaheen, R., Hertecant, J., Galadari, H. I., Albaqawi, B. S., Nabil, A., Alkuraya, F. S. <strong>On the phenotypic spectrum of serine biosynthesis.</strong> J. Inherit. Metab. Dis. 39: 373-381, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26960553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26960553</a>] [<a href="https://doi.org/10.1007/s10545-016-9921-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26960553">El-Hattab et al. (2016)</a>, <a href="#9" class="mim-tip-reference" title="Glinton, K. E., Benke, P. J., Lines, M. A., Geraghty, M. T., Chakraborty, P., Al-Dirbashi, O. Y., Jiang, Y., Kennedy, A. D., Grotewiel, M. S., Sutton, V. R., Elsea, S. H., El-Hattab, A. W. <strong>Disturbed phospholipid metabolism in serine biosynthesis defects revealed by metabolomic profiling.</strong> Molec. Genet. Metab. 123: 309-316, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29269105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29269105</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.12.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29269105">Glinton et al. (2017)</a> found low glycerophospholipids including low phosphatidylcholine, suggesting that PHGDH may play a role in CNS development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=26960553+28135894+29269105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 sibs, born to consanguineous parents from China, with PHGDHD, <a href="#8" class="mim-tip-reference" title="Fu, J., Chen, L., Su, T., Xu, S., Liu, Y. <strong>Mild phenotypes of phosphoglycerate dehydrogenase deficiency by a novel mutation of PHGDH gene: case report and literature review.</strong> Int. J. Dev. Neurosci. 83: 44-52, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36308023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36308023</a>] [<a href="https://doi.org/10.1002/jdn.10236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36308023">Fu et al. (2023)</a> identified homozygosity for a missense mutation (V404D; <a href="#0014">606879.0014</a>) in the regulatory domain of phosphoglycerate dehydrogenase. The authors reviewed the literature on pathogenic variants in the PHGDH gene; they noted 17 variants, mostly in the regulatory domain, associated with PHGDHD, and 13 variants, mostly located in the nucleotide-binding domain, associated with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36308023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with PHGDHD, <a href="#5" class="mim-tip-reference" title="Brassier, A., Valayannopoulos, V., Bahi-Buisson, N., Wiame, E., Hubert, L., Boddaert, N., Kaminska, A., Habarou, F., Desguerre, I., Van Schaftingen, E., Ottolenghi, C., de Lonlay, P. <strong>Two new cases of serine deficiency disorders treated with l-serine.</strong> Europ. J. Paediat. Neurol. 20: 53-60, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26610677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26610677</a>] [<a href="https://doi.org/10.1016/j.ejpn.2015.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26610677">Brassier et al. (2016)</a> identified compound heterozygous mutations in the PHGDH gene (R135W, <a href="#0004">606879.0004</a> and R163W, <a href="#0015">606879.0015</a>). The mutations were identified by sequencing of a 3-gene panel of genes associated with serine deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26610677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Neu-Laxova Syndrome 1</em></strong></p><p>
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In 3 patients from unrelated consanguineous Saudi families with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>), <a href="#14" class="mim-tip-reference" title="Shaheen, R., Rahbeeni, Z., Alhashem, A., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Al-Onazi, N., Al-Baqawi, B. S., Saleh, M. A., Alkuraya, F. S. <strong>Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.</strong> Am. J. Hum. Genet. 94: 898-904, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24836451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24836451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24836451[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.2014.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24836451">Shaheen et al. (2014)</a> identified 2 different homozygous missense mutations in the PHGDH gene (G140R; <a href="#0007">606879.0007</a> and R163Q; <a href="#0008">606879.0008</a>). The mutations were found by a combination of autozygosity mapping and exome sequencing. Both substitutions occurred at highly conserved residues within the NAD(P)-binding domain at the PHGDH dimer interface, suggesting that they would severely interfere with enzyme function. In vitro studies of the variants were not performed. In addition to manifesting classic features of the disorder, 1 of the patients had a dried blood spot that showed low concentrations of serine and glycine, consistent with a biochemical diagnosis of PHGDH deficiency. <a href="#14" class="mim-tip-reference" title="Shaheen, R., Rahbeeni, Z., Alhashem, A., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Al-Onazi, N., Al-Baqawi, B. S., Saleh, M. A., Alkuraya, F. S. <strong>Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.</strong> Am. J. Hum. Genet. 94: 898-904, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24836451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24836451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24836451[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.2014.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24836451">Shaheen et al. (2014)</a> suggested that the severe phenotype observed in these patients reflects the extreme end of the inborn error of serine metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24836451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others. <strong>Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.</strong> Am. J. Hum. Genet. 95: 285-293, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25152457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25152457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25152457[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.2014.07.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25152457">Acuna-Hidalgo et al. (2014)</a> identified biallelic mutations in the PHGDH gene (see, e.g., <a href="#0009">606879.0009</a> and <a href="#0010">606879.0010</a>) in affected individuals from 3 unrelated families with NLS1. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25152457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 fetuses with NLS1, conceived by Chinese parents, <a href="#4" class="mim-tip-reference" title="Bourque, D. K., Cloutier, M., Kernohan, K. D., Bareke, E., Grynspan, D., Michaud, J., Care4Rare Canada Consortium, Boycott, K. M. <strong>Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: the utility of exome sequencing in deciphering the diagnosis.</strong> Am. J. Med. Genet. 179A: 813-816, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30838783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30838783</a>] [<a href="https://doi.org/10.1002/ajmg.a.61076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30838783">Bourque et al. (2019)</a> identified homozygosity for a mutation in the PHGDH gene resulting in loss of the translation start codon (M1?; <a href="#0013">606879.0013</a>). The start methionine of the PHGDH gene is highly conserved among species, and only 1 transcript had been observed. Although the parents were not known to be related, homozygosity mapping identified an 11.2-Mb region on chromosome 1 shared by the 2 fetuses for which exome sequencing was performed, suggesting that the parents likely shared a distant common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30838783" 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> rs121907988 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121907988;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/rs121907988?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=rs121907988" 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=rs121907988" 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=RCV000004072 OR RCV001262594" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004072, RCV001262594" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004072...</a>
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<p>In a girl, born of a consanguineous Moroccan couple, who was reported by <a href="#12" class="mim-tip-reference" title="Pineda, M., Vilaseca, M. A., Artuch, R., Santos, S., Garcia Gonzales, M. M., Sau, I., Aracil, A., Van Schaftingen, E., Jaeken, J. <strong>3-Phosphoglycerate dehydrogenase deficiency in a patient with West syndrome.</strong> Dev. Med. Child Neurol. 42: 629-633, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11034457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11034457</a>] [<a href="https://doi.org/10.1017/s0012162200001171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11034457">Pineda et al. (2000)</a> to have phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>) and West syndrome, <a href="#10" class="mim-tip-reference" title="Klomp, L. W. J., de Koning, T. J., Malingre, H. E. M., van Beurden, E. A. C. M., Brink, M., Opdam, F. L., Duran, M., Jaeken, J., Pineda, M., van Maldergem, L., Poll-The, B. T., van den Berg, I. E. T., Berger, R. <strong>Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.</strong> Am. J. Hum. Genet. 67: 1389-1399, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055895</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055895[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055895">Klomp et al. (2000)</a> found a homozygous 1273G-A transition in the PHGDH gene, resulting in a val425-to-met substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11055895+11034457" 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> rs730882181 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs730882181;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/rs730882181?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=rs730882181" 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=rs730882181" 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=RCV000004073" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004073" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004073</a>
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<p>In a Dutch boy with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), <a href="#15" class="mim-tip-reference" title="Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., Klomp, L. W. J. <strong>Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.</strong> Hum. Mutat. 30: 749-756, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19235232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19235232</a>] [<a href="https://doi.org/10.1002/humu.20934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19235232">Tabatabaie et al. (2009)</a> identified compound heterozygosity for a 1-bp deletion (712delG) in exon 7 and a 403C-T transition in exon 4 of the PHGDH gene, the former causing a frameshift and premature termination codon and the latter resulting in an arg135-to-trp (R135W; <a href="#0004">606879.0004</a>) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a markedly decreased V(max). Transfection studies in HEK293 cells with the deletion mutant resulted in undetectable expression of 3-PGDH protein, whereas overexpression of the R135W mutant resulted in a moderate decrease of V(max) without affecting K(m). Molecular modeling of the R135W mutation onto the partial crystal structure of 3-PGDH predicted that the mutation would affect substrate and cofactor binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19235232" 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> rs267606949 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606949;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/rs267606949?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=rs267606949" 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=rs267606949" 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=RCV000004074 OR RCV000675113 OR RCV001171760" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004074, RCV000675113, RCV001171760" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004074...</a>
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<p>For discussion of the arg135-to-trp (R135W) mutation in the PHGDH gene that was found in compound heterozygous state in a patient with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>) by <a href="#15" class="mim-tip-reference" title="Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., Klomp, L. W. J. <strong>Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.</strong> Hum. Mutat. 30: 749-756, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19235232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19235232</a>] [<a href="https://doi.org/10.1002/humu.20934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19235232">Tabatabaie et al. (2009)</a>, see <a href="#0003">606879.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19235232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient (patient 1) with PHGDHD, <a href="#5" class="mim-tip-reference" title="Brassier, A., Valayannopoulos, V., Bahi-Buisson, N., Wiame, E., Hubert, L., Boddaert, N., Kaminska, A., Habarou, F., Desguerre, I., Van Schaftingen, E., Ottolenghi, C., de Lonlay, P. <strong>Two new cases of serine deficiency disorders treated with l-serine.</strong> Europ. J. Paediat. Neurol. 20: 53-60, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26610677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26610677</a>] [<a href="https://doi.org/10.1016/j.ejpn.2015.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26610677">Brassier et al. (2016)</a> identified compound heterozygous mutations in the PHGDH gene: the R135W mutations, which they said resulted from a c.403C-G transition, and a c.487C-T transition, resulting in an arg163-to-trp (R163W; <a href="#0015">606879.0015</a>) substitution. The mutations were identified by sequencing of a panel of 3 genes associated with serine deficiency; the mother was found to be a mutation carrier but the father was not available for testing. The patient had very low plasma and CSF serine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26610677" 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> rs267606948 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606948;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/rs267606948?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=rs267606948" 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=rs267606948" 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=RCV000004075 OR RCV000850583 OR RCV001659681 OR RCV003338379" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004075, RCV000850583, RCV001659681, RCV003338379" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004075...</a>
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<p>In a Dutch brother and sister with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), born of consanguineous parents, <a href="#15" class="mim-tip-reference" title="Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., Klomp, L. W. J. <strong>Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.</strong> Hum. Mutat. 30: 749-756, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19235232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19235232</a>] [<a href="https://doi.org/10.1002/humu.20934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19235232">Tabatabaie et al. (2009)</a> identified homozygosity for a 1129G-A transition in exon 10 of the PHGDH gene, resulting in a gly377-to-ser (G377S) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a markedly decreased V(max); transfection studies in HEK293 cells with overexpression of the G377S mutant resulted in a moderate decrease of V(max) without affecting K(m). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19235232" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 sisters (family 3) with PHGDHD, <a href="#3" class="mim-tip-reference" title="Benke, P. J., Hidalgo, R. J., Braffman, B. H., Jans, J., van Gassen, K. L. I., Sunbul, R., El-Hattab, A. W. <strong>Infantile serine biosynthesis defect due to phosphoglycerate dehydrogenase deficiency: variability in phenotype and treatment response, novel mutations, and diagnostic challenges.</strong> J. Child Neurol. 32: 543-549, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135894</a>] [<a href="https://doi.org/10.1177/0883073817690094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135894">Benke et al. (2017)</a> identified homozygosity for the c.1129G-A transition (c.1129G-A, NM_006623.3) in the PHGDH gene, resulting in a gly377-to-ser (G377S) substitution. In 2 sisters in an unrelated family (family 1) with PHGDHD, <a href="#3" class="mim-tip-reference" title="Benke, P. J., Hidalgo, R. J., Braffman, B. H., Jans, J., van Gassen, K. L. I., Sunbul, R., El-Hattab, A. W. <strong>Infantile serine biosynthesis defect due to phosphoglycerate dehydrogenase deficiency: variability in phenotype and treatment response, novel mutations, and diagnostic challenges.</strong> J. Child Neurol. 32: 543-549, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135894</a>] [<a href="https://doi.org/10.1177/0883073817690094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135894">Benke et al. (2017)</a> identified compound heterozygous mutations in the PHGDH gene: G377S and a 1-bp duplication (c.138+2dupT; <a href="#0012">606879.0012</a>). Serine and glycine were low in plasma and CSF in the patients from both families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28135894" 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">rs267606947 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606947;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=rs267606947" 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=rs267606947" 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=RCV000004076 OR RCV000662195 OR RCV002298432 OR RCV003441702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004076, RCV000662195, RCV002298432, RCV003441702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004076...</a>
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<p>In a Turkish boy with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), <a href="#15" class="mim-tip-reference" title="Tabatabaie, L., de Koning, T. J., Geboers, A. J. J. M., van den Berg, I. E. T., Berger, R., Klomp, L. W. J. <strong>Novel mutations in 3-phosphoglycerate dehydrogenase (PHGDH) are distributed throughout the protein and result in altered enzyme kinetics.</strong> Hum. Mutat. 30: 749-756, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19235232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19235232</a>] [<a href="https://doi.org/10.1002/humu.20934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19235232">Tabatabaie et al. (2009)</a> identified homozygosity for a 781G-A transition in exon 7 of the PHGDH gene, resulting in a val261-to-met (V261M) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a significant but incomplete reduction in V(max), whereas transfection studies in HEK293 cells with overexpression of the V261M mutant displayed a 4-fold increase in K(m). Molecular modeling of the V261M mutation onto the partial crystal structure of 3-PGDH predicted that the mutation would affect substrate and cofactor binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19235232" 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>.0007 NEU-LAXOVA SYNDROME 1</strong>
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PHGDH, GLY140ARG
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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> rs587777770 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777770;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/rs587777770?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=rs587777770" 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=rs587777770" 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=RCV000128433 OR RCV000171157 OR RCV002514704" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128433, RCV000171157, RCV002514704" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128433...</a>
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<p>In 2 unrelated patients, each born of consanguineous Saudi parents, with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>), <a href="#14" class="mim-tip-reference" title="Shaheen, R., Rahbeeni, Z., Alhashem, A., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Al-Onazi, N., Al-Baqawi, B. S., Saleh, M. A., Alkuraya, F. S. <strong>Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.</strong> Am. J. Hum. Genet. 94: 898-904, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24836451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24836451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24836451[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.2014.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24836451">Shaheen et al. (2014)</a> identified a homozygous c.418G-A transition in the PHGDH gene, resulting in a gly140-to-arg (G140R) substitution at a highly conserved residue within the NAD(P)-binding domain and at the PHGDH dimer interface. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Variant Server databases, or in 450 Saudi exomes. All 4 unaffected parents were heterozygous for the mutation. Functional studies of the variant were not performed. One of the affected infants died immediately after birth, and the other was stillborn at age 29 weeks. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24836451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<strong>.0008 NEU-LAXOVA SYNDROME 1</strong>
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PHGDH, ARG163GLN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777483 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777483;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=rs587777483" 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=rs587777483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000128434 OR RCV000675136 OR RCV002222400 OR RCV004019724" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000128434, RCV000675136, RCV002222400, RCV004019724" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000128434...</a>
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<p>In a male infant, born of consanguineous Saudi parents, with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>), <a href="#14" class="mim-tip-reference" title="Shaheen, R., Rahbeeni, Z., Alhashem, A., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Al-Onazi, N., Al-Baqawi, B. S., Saleh, M. A., Alkuraya, F. S. <strong>Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.</strong> Am. J. Hum. Genet. 94: 898-904, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24836451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24836451</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24836451[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.2014.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24836451">Shaheen et al. (2014)</a> identified a homozygous c.488G-A transition in the PHGDH gene, resulting in an arg163-to-gln (R163Q) substitution at a highly conserved residue within the NAD(P)-binding domain, specifically at the PHGDH dimer interface. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Variant Server databases, or in 450 Saudi exomes. Each unaffected parent was heterozygous for the mutation. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24836451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0009 NEU-LAXOVA SYNDROME 1</strong>
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PHGDH, GLU265LYS
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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> rs587777774 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777774;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/rs587777774?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=rs587777774" 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=rs587777774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000144444" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144444" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144444</a>
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<p>In a fetus, conceived by consanguineous parents, with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>), <a href="#1" class="mim-tip-reference" title="Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others. <strong>Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.</strong> Am. J. Hum. Genet. 95: 285-293, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25152457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25152457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25152457[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.2014.07.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25152457">Acuna-Hidalgo et al. (2014)</a> identified a homozygous c.793G-A transition in the PHGDH gene, resulting in a glu265-to-lys (E265K) substitution at a highly conserved residue in close proximity to the substrate binding domain. The mutation, which segregated with the disorder in the family, was not found in the Exome Variant Server database; functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25152457" 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>.0010 NEU-LAXOVA SYNDROME 1</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">rs587777775 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777775;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=rs587777775" 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=rs587777775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000144445" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144445" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144445</a>
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<p>In a fetus, conceived by consanguineous parents, with Neu-Laxova syndrome-1 (NLS1; <a href="/entry/256520">256520</a>), <a href="#1" class="mim-tip-reference" title="Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others. <strong>Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.</strong> Am. J. Hum. Genet. 95: 285-293, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25152457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25152457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25152457[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.2014.07.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25152457">Acuna-Hidalgo et al. (2014)</a> identified a homozygous c.856G-C transversion in the PHGDH gene, resulting in an ala286-to-pro (A286P) substitution at a highly conserved residue in close proximity to the substrate binding domain. The mutation, which segregated with the disorder in the family, was not found in the Exome Variant Server database; functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25152457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0011 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</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">rs1652276195 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1652276195;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=rs1652276195" 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=rs1652276195" 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=RCV001172237 OR RCV004798890" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001172237, RCV004798890" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001172237...</a>
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<p>In a 2-month-old male infant, born to parents who came from the same area in the United Arab Emirates, with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), <a href="#7" class="mim-tip-reference" title="El-Hattab, A. W., Shaheen, R., Hertecant, J., Galadari, H. I., Albaqawi, B. S., Nabil, A., Alkuraya, F. S. <strong>On the phenotypic spectrum of serine biosynthesis.</strong> J. Inherit. Metab. Dis. 39: 373-381, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26960553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26960553</a>] [<a href="https://doi.org/10.1007/s10545-016-9921-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26960553">El-Hattab et al. (2016)</a> identified a homozygous c.1286G-T transversion in the PHGDH gene, resulting in a gly429-to-val (G429V) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26960553" 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>.0012 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
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PHGDH, c.138+2dupT
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1650723432 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1650723432;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=rs1650723432" 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=rs1650723432" 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=RCV001172238" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001172238" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001172238</a>
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<p>For discussion of the 1-bp duplication (c.138+2dupT, NM_006623.3) in the PHGDH gene that was found in compound heterozygous state in 2 sisters (family 1) with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>) by <a href="#3" class="mim-tip-reference" title="Benke, P. J., Hidalgo, R. J., Braffman, B. H., Jans, J., van Gassen, K. L. I., Sunbul, R., El-Hattab, A. W. <strong>Infantile serine biosynthesis defect due to phosphoglycerate dehydrogenase deficiency: variability in phenotype and treatment response, novel mutations, and diagnostic challenges.</strong> J. Child Neurol. 32: 543-549, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135894</a>] [<a href="https://doi.org/10.1177/0883073817690094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135894">Benke et al. (2017)</a>, see <a href="#0005">606879.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28135894" 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>.0013 NEU-LAXOVA SYNDROME 1</strong>
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PHGDH, MET1?
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003093173 OR RCV003882739 OR RCV005021564" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003093173, RCV003882739, RCV005021564" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003093173...</a>
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<p>By exome sequencing in 3 fetuses, conceived by Chinese parents, with Neu-Laxova syndrome (NLS1; <a href="/entry/256520">256520</a>), <a href="#4" class="mim-tip-reference" title="Bourque, D. K., Cloutier, M., Kernohan, K. D., Bareke, E., Grynspan, D., Michaud, J., Care4Rare Canada Consortium, Boycott, K. M. <strong>Neu-Laxova syndrome presenting prenatally with increased nuchal translucency and cystic hygroma: the utility of exome sequencing in deciphering the diagnosis.</strong> Am. J. Med. Genet. 179A: 813-816, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30838783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30838783</a>] [<a href="https://doi.org/10.1002/ajmg.a.61076" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30838783">Bourque et al. (2019)</a> identified a homozygous c.1A-C transversion (c.1A-C, NM_006623.3) in the PHGDH gene, resulting in loss of the translation start codon (Met1?). The start methionine of the PHGDH gene is highly conserved among species, and only 1 transcript has been observed. The variant was not present in the gnomAD database. The variant was classified as likely pathogenic by ACMG criteria. Although the parents were not known to be related, homozygosity mapping identified an 11.2-Mb region on chromosome 1 shared by the 2 fetuses for which exome sequencing was performed, suggesting that the parents likely shared a distant common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30838783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0014" class="mim-anchor"></a>
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<h4>
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<strong>.0014 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
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</h4>
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PHGDH, VAL404ASP
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003882749" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003882749" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003882749</a>
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<p>By exome sequencing in 2 sibs, born to consanguineous parents from China, with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>), <a href="#8" class="mim-tip-reference" title="Fu, J., Chen, L., Su, T., Xu, S., Liu, Y. <strong>Mild phenotypes of phosphoglycerate dehydrogenase deficiency by a novel mutation of PHGDH gene: case report and literature review.</strong> Int. J. Dev. Neurosci. 83: 44-52, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36308023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36308023</a>] [<a href="https://doi.org/10.1002/jdn.10236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36308023">Fu et al. (2023)</a> identified homozygosity for a c.1211T-A transversion (c.1211T-A, NM_006623.4) in exon 11 of the PHGDH gene, resulting in a val404-to-asp (V404D) substitution in the regulatory domain. Both parents were heterozygous for the variant, which was confirmed by Sanger sequencing. The variant was not present in the gnomAD or ExAC databases and was classified as likely pathogenic by ACMG criteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36308023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0015" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0015 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
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PHGDH, ARG163TRP
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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> rs772067625 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs772067625;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/rs772067625?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=rs772067625" 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=rs772067625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000436610 OR RCV001833521 OR RCV003338583" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000436610, RCV001833521, RCV003338583" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000436610...</a>
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<p>For discussion of the c.487C-T transition in the PHGDH gene, resulting in an arg163-to-trp (R163W) substitution, that was identified in compound heterozygous state in a patient (patient 1) with phosphoglycerate dehydrogenase deficiency (PHGDHD; <a href="/entry/601815">601815</a>) by <a href="#5" class="mim-tip-reference" title="Brassier, A., Valayannopoulos, V., Bahi-Buisson, N., Wiame, E., Hubert, L., Boddaert, N., Kaminska, A., Habarou, F., Desguerre, I., Van Schaftingen, E., Ottolenghi, C., de Lonlay, P. <strong>Two new cases of serine deficiency disorders treated with l-serine.</strong> Europ. J. Paediat. Neurol. 20: 53-60, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26610677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26610677</a>] [<a href="https://doi.org/10.1016/j.ejpn.2015.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26610677">Brassier et al. (2016)</a>, see <a href="#0004">606879.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26610677" 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 id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Acuna-Hidalgo2014" class="mim-anchor"></a>
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Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others.
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<strong>Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.</strong>
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Am. J. Hum. Genet. 95: 285-293, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25152457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25152457</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25152457[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=25152457" 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.2014.07.012" target="_blank">Full Text</a>]
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<a id="Baek2000" class="mim-anchor"></a>
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Baek, J. Y., Jun, D. Y., Taub, D., Kim, Y. H.
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<strong>Assignment of human 3-phosphoglycerate dehydrogenase (PHGDH) to human chromosome band 1p12 by fluorescence in situ hybridization.</strong>
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Cytogenet. Cell Genet. 89: 6-7, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10894924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10894924</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10894924" 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/10.1159/000015577" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<a id="Benke2017" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1177/0883073817690094" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61076" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ejpn.2015.10.007" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0378-1119(00)00009-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10545-016-9921-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/jdn.10236" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2017.12.009" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/316886" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng.890" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1017/s0012162200001171" target="_blank">Full Text</a>]
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Possemato, R., Marks, K. M., Shaul, Y. D., Pacold, M. E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.-K., Jang, H. G., Jha, A. K., Chen, W. W., Barrett, F. G., and 15 others.
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<strong>Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.</strong>
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[<a href="https://doi.org/10.1038/nature10350" target="_blank">Full Text</a>]
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Shaheen, R., Rahbeeni, Z., Alhashem, A., Faqeih, E., Zhao, Q., Xiong, Y., Almoisheer, A., Al-Qattan, S. M., Almadani, H. A., Al-Onazi, N., Al-Baqawi, B. S., Saleh, M. A., Alkuraya, F. S.
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[<a href="https://doi.org/10.1016/j.ajhg.2014.04.015" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20934" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 04/08/2024
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Sonja A. Rasmussen - updated : 02/26/2024<br>Hilary J. Vernon - updated : 06/04/2020<br>Cassandra L. Kniffin - updated : 9/30/2014<br>Cassandra L. Kniffin - updated : 6/23/2014<br>Ada Hamosh - updated : 10/7/2011<br>Ada Hamosh - updated : 9/6/2011<br>Marla J. F. O'Neill - updated : 3/5/2010<br>Ada Hamosh - updated : 10/6/2003
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alopez : 02/27/2024<br>carol : 02/27/2024<br>alopez : 02/26/2024<br>carol : 06/05/2020<br>carol : 06/04/2020<br>carol : 03/04/2015<br>mcolton : 3/3/2015<br>carol : 10/2/2014<br>mcolton : 10/1/2014<br>ckniffin : 9/30/2014<br>carol : 6/26/2014<br>mcolton : 6/25/2014<br>ckniffin : 6/23/2014<br>alopez : 10/13/2011<br>terry : 10/7/2011<br>alopez : 9/7/2011<br>terry : 9/6/2011<br>wwang : 3/8/2010<br>terry : 3/5/2010<br>wwang : 3/2/2005<br>carol : 10/31/2003<br>carol : 10/31/2003<br>cwells : 10/6/2003<br>mgross : 4/25/2002<br>carol : 4/24/2002<br>carol : 4/24/2002
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606879
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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PHOSPHOGLYCERATE DEHYDROGENASE; PHGDH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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3-PHOSPHOGLYCERATE DEHYDROGENASE; 3PGDH
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PHGDH</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 1p12
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:119,711,934-119,744,215 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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1p12
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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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Neu-Laxova syndrome 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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256520
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Phosphoglycerate dehydrogenase deficiency
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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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601815
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>3-Phosphoglycerate dehydrogenase (PHGDH; EC 1.1.1.95) catalyzes the transition of 3-phosphoglycerate into 3-phosphohydroxypyruvate, which is the first and rate-limiting step in the phosphorylated pathway of serine biosynthesis, using NAD+/NADH as a cofactor (summary by Cho et al., 2000). </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>Cho et al. (2000) cloned a cDNA encoding phosphoglycerate dehydrogenase from a human Jurkat T-cell cDNA library. The deduced 533-amino acid protein, with a molecular mass of 56.8 kD, shares 94% sequence identity with rat liver 3-PGDH. Northern blot analysis detected a major 2.1-kb transcript at high levels in prostate, testis, ovary, brain, liver, kidney, and pancreas and at low levels in thymus, colon, and heart. A 710-bp transcript appeared as a weaker band in most tissues in which the 2.1-kb mRNA was expressed, was more significant than the 2.1-kb mRNA in heart, and was the only transcript present in skeletal muscle. The 2.1-kb transcript was also detected in most continuously growing tumor cells tested. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Cho et al. (2000) found that TPA-induced monocytic differentiation of U937 cells, which also resulted in growth arrest, abruptly downregulated the expression of PHGDH. Removal of TPA restored cell growth through the retrodifferentiation process and subsequent expression of PHGDH. These findings suggested that the expression of PHGDH may be regulated at the transcriptional level depending on tissue specificity and cellular proliferative status. </p><p>Possemato et al. (2011) developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, they screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, PHGDH is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of estrogen receptor-negative breast cancers. PHGDH catalyzes the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, caused a strong decrease in cell proliferation and a reduction in serine synthesis. Possemato et al. (2011) found that PHGDH suppression does not affect intracellular serine levels, but causes a drop in levels of alpha-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. Possemato et al. (2011) concluded that certain breast cancers are dependent on increased serine pathway flux caused by PHGDH overexpression. </p><p>Locasale et al. (2011) found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through PHGDH. An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal number copy gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Locasale et al. (2011) concluded that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer. </p>
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</span>
|
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<div>
|
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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|
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|
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|
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<span class="mim-text-font">
|
|
<p>Using 2 radiation hybrid panels, Klomp et al. (2000) mapped the PHGDH gene to chromosome 1q12. However, by fluorescence in situ hybridization, Baek et al. (2000) mapped the PHGDH gene to 1p12. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
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</div>
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|
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|
|
<span class="mim-text-font">
|
|
<p><strong><em>Phosphoglycerate Dehydrogenase Deficiency</em></strong></p><p>
|
|
To investigate the molecular basis of phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), Klomp et al. (2000) characterized the PHGDH mRNA sequence and analyzed it for variations in 6 patients from 4 families with this disorder. Five patients in 3 different families were homozygous for a val490-to-met (V490M; 606879.0001) mutation and the sixth patient was homozygous for a val425-to-met (V425M; 606879.0002) mutation. Both mutations were located in the C terminus of the PHGDH gene. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurologic impairment in these patients, the data suggested an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system. </p><p>Tabatabaie et al. (2009) identified 1 frameshift and 4 missense mutations in the PHGDH gene in 5 patients with phosphoglycerate dehydrogenase deficiency (see, e.g., 606879.0003-606879.0006). Studies in patient fibroblasts showed significant, but incomplete, reduction with missense mutations, including the previously identified V490M and V425M substitutions. Transient overexpression studies in HEK293 cells and molecular modeling onto the partial crystal structure of 3-PGDH suggested that missense mutations associated with 3-PGDH deficiency either primarily affect substrate binding or result in very low residual enzymatic activity. </p><p>In a 2-month-old male infant, born to parents who came from the same area in the United Arab Emirates, with PHGDH deficiency, El-Hattab et al. (2016) identified a homozygous missense mutation in the PHGDH gene (G429V; 606879.0011). </p><p>In 5 individuals with PHGDHD from 2 unrelated families, Benke et al. (2017) identified homozygous or compound heterozygous mutations in the PHGDH gene (606879.0005 and 606879.0012). Studies in patient fibroblasts showed decreased PHGDH enzyme activity compared to control. Serine and glycine were low in patient plasma and CSF. By metabolomic analysis in plasma from these sisters and the boy previously reported by El-Hattab et al. (2016), Glinton et al. (2017) found low glycerophospholipids including low phosphatidylcholine, suggesting that PHGDH may play a role in CNS development. </p><p>In 2 sibs, born to consanguineous parents from China, with PHGDHD, Fu et al. (2023) identified homozygosity for a missense mutation (V404D; 606879.0014) in the regulatory domain of phosphoglycerate dehydrogenase. The authors reviewed the literature on pathogenic variants in the PHGDH gene; they noted 17 variants, mostly in the regulatory domain, associated with PHGDHD, and 13 variants, mostly located in the nucleotide-binding domain, associated with Neu-Laxova syndrome-1 (NLS1; 256520). </p><p>In a patient with PHGDHD, Brassier et al. (2016) identified compound heterozygous mutations in the PHGDH gene (R135W, 606879.0004 and R163W, 606879.0015). The mutations were identified by sequencing of a 3-gene panel of genes associated with serine deficiency. </p><p><strong><em>Neu-Laxova Syndrome 1</em></strong></p><p>
|
|
In 3 patients from unrelated consanguineous Saudi families with Neu-Laxova syndrome-1 (NLS1; 256520), Shaheen et al. (2014) identified 2 different homozygous missense mutations in the PHGDH gene (G140R; 606879.0007 and R163Q; 606879.0008). The mutations were found by a combination of autozygosity mapping and exome sequencing. Both substitutions occurred at highly conserved residues within the NAD(P)-binding domain at the PHGDH dimer interface, suggesting that they would severely interfere with enzyme function. In vitro studies of the variants were not performed. In addition to manifesting classic features of the disorder, 1 of the patients had a dried blood spot that showed low concentrations of serine and glycine, consistent with a biochemical diagnosis of PHGDH deficiency. Shaheen et al. (2014) suggested that the severe phenotype observed in these patients reflects the extreme end of the inborn error of serine metabolism. </p><p>Acuna-Hidalgo et al. (2014) identified biallelic mutations in the PHGDH gene (see, e.g., 606879.0009 and 606879.0010) in affected individuals from 3 unrelated families with NLS1. Functional studies of the variants were not performed. </p><p>In 3 fetuses with NLS1, conceived by Chinese parents, Bourque et al. (2019) identified homozygosity for a mutation in the PHGDH gene resulting in loss of the translation start codon (M1?; 606879.0013). The start methionine of the PHGDH gene is highly conserved among species, and only 1 transcript had been observed. Although the parents were not known to be related, homozygosity mapping identified an 11.2-Mb region on chromosome 1 shared by the 2 fetuses for which exome sequencing was performed, suggesting that the parents likely shared a distant common ancestor. </p>
|
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</span>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>15 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</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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PHGDH, VAL490MET
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<br />
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|
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SNP: rs121907987,
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gnomAD: rs121907987,
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ClinVar: RCV000004071, RCV002251869, RCV002482824, RCV003338378, RCV004757095
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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 5 patients from 3 different families (2 Turkish and 1 European), Klomp et al. (2000) found that PHGDH deficiency (PHGDHD; 601815) was related to a homozygous 1468G-A transition predicted to cause a val490-to-met amino acid substitution in the protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</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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PHGDH, VAL425MET
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<br />
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|
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SNP: rs121907988,
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gnomAD: rs121907988,
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ClinVar: RCV000004072, RCV001262594
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a girl, born of a consanguineous Moroccan couple, who was reported by Pineda et al. (2000) to have phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815) and West syndrome, Klomp et al. (2000) found a homozygous 1273G-A transition in the PHGDH gene, resulting in a val425-to-met substitution. </p>
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|
</span>
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</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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PHGDH, 1-BP DEL, 712G
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<br />
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SNP: rs730882181,
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gnomAD: rs730882181,
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ClinVar: RCV000004073
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a Dutch boy with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), Tabatabaie et al. (2009) identified compound heterozygosity for a 1-bp deletion (712delG) in exon 7 and a 403C-T transition in exon 4 of the PHGDH gene, the former causing a frameshift and premature termination codon and the latter resulting in an arg135-to-trp (R135W; 606879.0004) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a markedly decreased V(max). Transfection studies in HEK293 cells with the deletion mutant resulted in undetectable expression of 3-PGDH protein, whereas overexpression of the R135W mutant resulted in a moderate decrease of V(max) without affecting K(m). Molecular modeling of the R135W mutation onto the partial crystal structure of 3-PGDH predicted that the mutation would affect substrate and cofactor binding. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0004 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</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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PHGDH, ARG135TRP
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<br />
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SNP: rs267606949,
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|
|
|
gnomAD: rs267606949,
|
|
|
|
|
|
ClinVar: RCV000004074, RCV000675113, RCV001171760
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg135-to-trp (R135W) mutation in the PHGDH gene that was found in compound heterozygous state in a patient with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815) by Tabatabaie et al. (2009), see 606879.0003. </p><p>In a patient (patient 1) with PHGDHD, Brassier et al. (2016) identified compound heterozygous mutations in the PHGDH gene: the R135W mutations, which they said resulted from a c.403C-G transition, and a c.487C-T transition, resulting in an arg163-to-trp (R163W; 606879.0015) substitution. The mutations were identified by sequencing of a panel of 3 genes associated with serine deficiency; the mother was found to be a mutation carrier but the father was not available for testing. The patient had very low plasma and CSF serine. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
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|
|
<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
<div>
|
|
<span class="mim-text-font">
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PHGDH, GLY377SER
|
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|
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|
<br />
|
|
|
|
SNP: rs267606948,
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|
|
gnomAD: rs267606948,
|
|
|
|
|
|
ClinVar: RCV000004075, RCV000850583, RCV001659681, RCV003338379
|
|
|
|
|
|
</span>
|
|
</div>
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|
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|
<div>
|
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<span class="mim-text-font">
|
|
<p>In a Dutch brother and sister with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), born of consanguineous parents, Tabatabaie et al. (2009) identified homozygosity for a 1129G-A transition in exon 10 of the PHGDH gene, resulting in a gly377-to-ser (G377S) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a markedly decreased V(max); transfection studies in HEK293 cells with overexpression of the G377S mutant resulted in a moderate decrease of V(max) without affecting K(m). </p><p>In 3 sisters (family 3) with PHGDHD, Benke et al. (2017) identified homozygosity for the c.1129G-A transition (c.1129G-A, NM_006623.3) in the PHGDH gene, resulting in a gly377-to-ser (G377S) substitution. In 2 sisters in an unrelated family (family 1) with PHGDHD, Benke et al. (2017) identified compound heterozygous mutations in the PHGDH gene: G377S and a 1-bp duplication (c.138+2dupT; 606879.0012). Serine and glycine were low in plasma and CSF in the patients from both families. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
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|
PHGDH, VAL261MET
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|
<br />
|
|
|
|
SNP: rs267606947,
|
|
|
|
|
|
|
|
ClinVar: RCV000004076, RCV000662195, RCV002298432, RCV003441702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish boy with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), Tabatabaie et al. (2009) identified homozygosity for a 781G-A transition in exon 7 of the PHGDH gene, resulting in a val261-to-met (V261M) substitution. Analysis of enzyme kinetics in patient-derived fibroblasts showed a significant but incomplete reduction in V(max), whereas transfection studies in HEK293 cells with overexpression of the V261M mutant displayed a 4-fold increase in K(m). Molecular modeling of the V261M mutation onto the partial crystal structure of 3-PGDH predicted that the mutation would affect substrate and cofactor binding. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</div>
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NEU-LAXOVA SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
<div>
|
|
<span class="mim-text-font">
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|
|
|
PHGDH, GLY140ARG
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|
<br />
|
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|
|
SNP: rs587777770,
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|
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|
|
|
gnomAD: rs587777770,
|
|
|
|
|
|
ClinVar: RCV000128433, RCV000171157, RCV002514704
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients, each born of consanguineous Saudi parents, with Neu-Laxova syndrome-1 (NLS1; 256520), Shaheen et al. (2014) identified a homozygous c.418G-A transition in the PHGDH gene, resulting in a gly140-to-arg (G140R) substitution at a highly conserved residue within the NAD(P)-binding domain and at the PHGDH dimer interface. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Variant Server databases, or in 450 Saudi exomes. All 4 unaffected parents were heterozygous for the mutation. Functional studies of the variant were not performed. One of the affected infants died immediately after birth, and the other was stillborn at age 29 weeks. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NEU-LAXOVA SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, ARG163GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777483,
|
|
|
|
|
|
|
|
ClinVar: RCV000128434, RCV000675136, RCV002222400, RCV004019724
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male infant, born of consanguineous Saudi parents, with Neu-Laxova syndrome-1 (NLS1; 256520), Shaheen et al. (2014) identified a homozygous c.488G-A transition in the PHGDH gene, resulting in an arg163-to-gln (R163Q) substitution at a highly conserved residue within the NAD(P)-binding domain, specifically at the PHGDH dimer interface. The mutation, which was found by a combination of autozygosity mapping and exome sequencing and confirmed by Sanger sequencing, was not present in the 1000 Genomes Project or Exome Variant Server databases, or in 450 Saudi exomes. Each unaffected parent was heterozygous for the mutation. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NEU-LAXOVA SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, GLU265LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777774,
|
|
|
|
|
|
gnomAD: rs587777774,
|
|
|
|
|
|
ClinVar: RCV000144444
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a fetus, conceived by consanguineous parents, with Neu-Laxova syndrome-1 (NLS1; 256520), Acuna-Hidalgo et al. (2014) identified a homozygous c.793G-A transition in the PHGDH gene, resulting in a glu265-to-lys (E265K) substitution at a highly conserved residue in close proximity to the substrate binding domain. The mutation, which segregated with the disorder in the family, was not found in the Exome Variant Server database; functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 NEU-LAXOVA SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, ALA286PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777775,
|
|
|
|
|
|
|
|
ClinVar: RCV000144445
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a fetus, conceived by consanguineous parents, with Neu-Laxova syndrome-1 (NLS1; 256520), Acuna-Hidalgo et al. (2014) identified a homozygous c.856G-C transversion in the PHGDH gene, resulting in an ala286-to-pro (A286P) substitution at a highly conserved residue in close proximity to the substrate binding domain. The mutation, which segregated with the disorder in the family, was not found in the Exome Variant Server database; functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, GLY429VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1652276195,
|
|
|
|
|
|
|
|
ClinVar: RCV001172237, RCV004798890
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-month-old male infant, born to parents who came from the same area in the United Arab Emirates, with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), El-Hattab et al. (2016) identified a homozygous c.1286G-T transversion in the PHGDH gene, resulting in a gly429-to-val (G429V) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, c.138+2dupT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1650723432,
|
|
|
|
|
|
|
|
ClinVar: RCV001172238
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp duplication (c.138+2dupT, NM_006623.3) in the PHGDH gene that was found in compound heterozygous state in 2 sisters (family 1) with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815) by Benke et al. (2017), see 606879.0005. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 NEU-LAXOVA SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, MET1?
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003093173, RCV003882739, RCV005021564
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing in 3 fetuses, conceived by Chinese parents, with Neu-Laxova syndrome (NLS1; 256520), Bourque et al. (2019) identified a homozygous c.1A-C transversion (c.1A-C, NM_006623.3) in the PHGDH gene, resulting in loss of the translation start codon (Met1?). The start methionine of the PHGDH gene is highly conserved among species, and only 1 transcript has been observed. The variant was not present in the gnomAD database. The variant was classified as likely pathogenic by ACMG criteria. Although the parents were not known to be related, homozygosity mapping identified an 11.2-Mb region on chromosome 1 shared by the 2 fetuses for which exome sequencing was performed, suggesting that the parents likely shared a distant common ancestor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, VAL404ASP
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003882749
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By exome sequencing in 2 sibs, born to consanguineous parents from China, with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815), Fu et al. (2023) identified homozygosity for a c.1211T-A transversion (c.1211T-A, NM_006623.4) in exon 11 of the PHGDH gene, resulting in a val404-to-asp (V404D) substitution in the regulatory domain. Both parents were heterozygous for the variant, which was confirmed by Sanger sequencing. The variant was not present in the gnomAD or ExAC databases and was classified as likely pathogenic by ACMG criteria. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 PHOSPHOGLYCERATE DEHYDROGENASE DEFICIENCY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
PHGDH, ARG163TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs772067625,
|
|
|
|
|
|
gnomAD: rs772067625,
|
|
|
|
|
|
ClinVar: RCV000436610, RCV001833521, RCV003338583
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.487C-T transition in the PHGDH gene, resulting in an arg163-to-trp (R163W) substitution, that was identified in compound heterozygous state in a patient (patient 1) with phosphoglycerate dehydrogenase deficiency (PHGDHD; 601815) by Brassier et al. (2016), see 606879.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Acuna-Hidalgo, R., Schanze, D., Kariminejad, A., Nordgren, A., Kariminejad, M. H., Conner, P., Grigelioniene, G., Nilsson, D., Nordenskjold, M., Wedell, A., Freyer, C., Wredenberg, A., and 18 others.
|
|
<strong>Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway.</strong>
|
|
Am. J. Hum. Genet. 95: 285-293, 2014.
|
|
|
|
|
|
[PubMed: 25152457]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2014.07.012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baek, J. Y., Jun, D. Y., Taub, D., Kim, Y. H.
|
|
<strong>Assignment of human 3-phosphoglycerate dehydrogenase (PHGDH) to human chromosome band 1p12 by fluorescence in situ hybridization.</strong>
|
|
Cytogenet. Cell Genet. 89: 6-7, 2000.
|
|
|
|
|
|
[PubMed: 10894924]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000015577]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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